Abstract
Acne vulgaris is a very common skin disease. Most patients present with mild to moderate acne comedonica or papulopustulosa grade I—II. The first-line treatment for these cases is generally via the topical route, whereas systemic medication is indicated when higher severity grades with small nodes or scarring occur. There are several topical agents available that affect at least one of the main pathogenetic factors responsible for the development of acne: hyperseborrhoea, hyperkeratosis, microbial colonisation and inflammatory and immunological reactions. Topical retinoids have a comedolytic and anticomedogenic activity, and some of them have anti-inflammatory potency. Azelaic acid and benzoyl peroxide have a moderate to strong antibacterial effect without inducing bacterial resistance, which is becoming a significant problem with the increasing use of topical antibacterials. Topical antiandrogens may soon be available for the treatment of the pathogenetic factor hyperseborrhoea.
The transdermal penetration and the resulting systemic bioavailability of the various topical agents has not been widely considered. Apart from the retinoids, which can be associated with the risk of embryotoxicity/teratogenicity, and Clindamycin, which might cause pseudomembranous colitis, information on the systemic pharmacokinetics of other topical agents is not readily available. There is still no consensus on the safe use of topical retinoids in pregnancy, and the occurrence of pseudomembranous colitis after the topical use of Clindamycin does not appear to be of clinical relevance. In general, topical anti-acne agents are well tolerated and, as would be expected from their limited transdermal uptake, other significant safety concerns have not so far arisen.
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References
Shalita A. The integral role of topical and oral retinoids in the early treatment of acne. J Eur Acad Dermatol Venereol 2001; 15 Suppl. 3: 43–9
Thiboutot D. New treatments and therapeutic strategies for acne. Arch Fam Med 2000 Feb; 9: 179–87
Cunliffe WJ, Gollnick HPM. Acne: diagnosis and management. London: Martin Dunitz, 2001
Plewig G, Kligman AM. Acne and rosacea. 4th ed. Berlin: Springer Verlag, 2002
Gollnick H. Current concepts of the pathenogenesis of acne: implications for drug treatment. Drugs 2003; 63(15): 1579–96
Russell JJ. Topical therapy for acne. Am Fam Physician 2000 Jan 15; 61: 357–66
Gollnick H, Schramm M. Topical drug treatment in acne. Dermatology 1998; 196:119–25
Tschan T, Steffen H, Supersaxo A. Sebaceous-gland deposition of Isotretinoin after topical application: an in vitro study using human facial skin. Skin Pharmacol 1997; 10: 126–34
Schaefer H, Slatery JT, Frant TJ. Follicular penetration. In: Scott RD, Guy RH, Hadgraft J, editors. Prediction of percutaneous penetration: methods, measurements, modeling. London: IBC Technical Services, 1990: 163–73
Van Hoogdalem EJ. Transdermal absorption of topical anti-acne agents in man; review of clinical pharmacokinetic data. J Eur Acad Dermatol Venereol 1998 Sep; 11 Suppl. 1: S13–9
Stuttgen G. Historical perspectives of tretinoin. J Am Acad Dermatol 1986 Oct; 15(4 Pt 2): 735–40
Zouboulis CC, Orfanos CE. Retinoids. In: Millikan LE, editor. Drug therapy in dermatology. New Orleans (LA): Dekker, 2000: 171–233
Gollnick H, Schramm M. Topical therapy in acne. J Eur Acad Dermatol Venereol 1998 Sep; 11 Suppl. 1: S8–12
Leid M, Kastner P, Chambon P. Multiplicity generates diversity in the retinoic acid signalling pathways. Trends Biochem Sci 1992 Oct; 17: 427–33
Zouboulis CC. Retinoids: which dermatological indications will benefit in the near future? Skin Pharmacol Appl Skin Physiol 2001 Sep—Oct; 14: 303–15
Nagpal S, Chandraratna RA. Recent developments in receptorselective retinoids. Curr Pharm Des 2000 Jun; 6: 919–31
Griffiths CE, Voorhees JJ. Human in vivo pharmacology of topical retinoids. Arch Dermatol Res 1994; 287: 53–60
Chandraratna RA. Future trends: a new generation of retinoids. J Am Acad Dermatol 1998 Oct; 39(4 Pt 2): S149–52
Nagpal S, Cai J, Zheng T, et al. Retinoid antagonism of NF-IL6: insight into the mechanism of antiproliferative effects of retinoids in Kaposi’s sarcoma. Mol Cell Biol 1997 Jul; 17: 4159–68
Nagpal S, Athanikar J, Chandraratna RA. Separation of transactivation and API antagonism functions of retinoic acid receptor alpha. J Biol Chem 1995 Jan 13; 270: 923–7
Gollnick HP, Dummler U. Retinoids. Clin Dermatol 1997 Sep–Oct; 15: 799–810
Orfanos CE, Zouboulis CC, Almond-Roesler B, et al. Current use and future potential role of retinoids in dermatology. Drugs 1997 Mar; 53: 358–88
Thielitz A, Helmdach M, Ropke EM, et al. Lipid analysis of follicular casts from cyanoacrylate strips as a new method for studying therapeutic effects of antiacne agents. Br J Dermatol 2001 Jul; 145: 19–27
Fulton J, Farzad-Bakshandeh A, Bradley S. Studies on the mechanism of action of topical benzoyl peroxide and vitamin A acid in acne vulgaris. J Cutan Pathol 1974; 1: 191–200
Kligman A, Fulton J, Plewig G. Topical vitamin A acid in acne vulgaris. Arch Dermatol 1969; 99: 469–76
Lammer EJ, Chen DT, Hoar RM, et al. Retinoic acid embryopathy. N Engl J Med 1985 Oct 3; 313: 837–41
Lipson AH, Collins F, Webster WS. Multiple congenital defects associated with maternal use of topical tretinoin. Lancet 1993 May 22; 341: 1352–3
Camera G, Pregliasco P. Ear malformation in baby born to mother using tretinoin cream [letter]. Lancet 1992; 339: 687
Rosa F. Retinoid embryopathy in humans. In: Karen G, editor. Retinoids in clinical practice. New York (NY): Dekker, 1992: 77–109
Jick SS, Terris BZ, Jick H. First trimester topical tretinoin and congenital disorders. Lancet 1993 May 8; 341: 1181–2
Clewell III HJ, Andersen ME, Wills RJ, et al. A physiologically based pharmacokinetic model for retinoic acid and its metabolites. J Am Acad Dermatol 1997 Mar; 36(3 Pt 2): S77–85
Nau H. Embryotoxicity and teratogenicity of topical retinoic acid. Skin Pharmacol 1993; 6 Suppl. 1: 35–44
Jick H. Retinoids and teratogenicity. J Am Acad Dermatol 1998 Aug; 39(2 Pt 3): S118–22
Griffiths CE, Finkel LJ, Ditre CM, et al. Topical tretinoin (retinoic acid) improves melasma: a vehicle-controlled, clinical trial. Br J Dermatol 1993 Oct; 129: 415–21
Zheng ZS, Polakowska R, Johnson A, et al. Transcriptional control of epidermal growth factor receptor by retinoic acid. Cell Growth Differ 1992 Apr; 3: 225–32
Tong PS, Horowitz NN, Wheeler LA. Trans retinoic acid enhances the growth response of epidermal keratinocytes to epidermal growth factor and transforming growth factor beta. J Invest Dermatol 1990 Jan; 94: 126–31
Fisher GJ, Esmann J, Griffiths CE, et al. Cellular, immunologic and biochemical characterization of topical retinoic acid-treated human skin. J Invest Dermatol 1991 May; 96: 699–707
Craven NM, Griffiths CE. Topical retinoids and cutaneous biology. Clin Exp Dermatol 1996 Jan; 21: 1–10
Griffiths CE, Russman AN, Majmudar G, et al. Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid). N Engl J Med 1993 Aug 19; 329: 530–5
Fisher GJ, Talwar HS, Lin J, et al. Molecular mechanisms of photoaging in human skin in vivo and their prevention by alltrans retinoic acid. Photochem Photobiol 1999 Feb; 69: 154–7
Tormä H. Interaction of Isotretinoin with endogenous retinoids. J Am Acad Dermatol 2001 Nov; 45: S143–9
Jurukovski V, Markova NG, Karaman-Jurukovska N, et al. Cloning and characterization of retinol dehydrogenase transcripts expressed in human epidermal keratinocytes. Mol Genet Metab 1999 May; 67: 62–73
Boerman MH, Napoli JL. Effects of sulfhydryl reagents, retinoids, and solubilization on the activity of microsomal retinol dehydrogenase. Arch Biochem Biophys 1995 Aug 20; 321: 434–41
Kim SY, Yoo SJ, Kwon HJ, et al. Retinoic acid 4-hydroxylasemediated catabolism of all-trans retinoic acid and the cell proliferation in head and neck squamous cell carcinoma. Metabolism 2002; 51(4): 477–81
Smith G, Wolf CR, Deeni YY, et al. Cutaneous expression o f cytochrome P450 CYP2S1: individuality in regulation by therpeutic agents for psoriasis and other skin diseases. Lancet 2003; 361(9366): 1336–43
Duell EA, Astrom A, Griffiths CE, et al. Human skin levels of retinoic acid and cytochrome P-450-derived 4-hydroxyretinoic acid after topical application of retinoic acid in vivo compared to concentrations required to stimulate retinoic acid receptormediated transcription in vitro. J Clin Invest 1992 Oct; 90: 1269–74
Shroot B. Pharmacodynamics and pharmacokinetics of topical adapalene. J Am Acad Dermatol 1998 Aug; 39(2 Pt 3): S17–24
Skov MJ, Quigley JW, Bucks DA. Topical delivery system for tretinoin: research and clinical implications. J Pharm Sci 1997 Oct; 86: 1138–43
Lucky AW, Cullen SI, Jarratt MT, et al. Comparative efficacy and safety of two 0.025% tretinoin gels: results from a multicenter double-blind, parallel study. J Am Acad Dermatol 1998 Apr; 38: S17–23
Quigley JW, Bucks DA. Reduced skin irritation with tretinoin containing polyolprepolymer-2, a new topical tretinoin delivery system: a summary of preclinical and clinical investigations. J Am Acad Dermatol 1998 Apr; 38: S5–10
Embil K, Nacht S. The Microsponge Delivery System (MDS): a topical delivery system with reduced irritancy incorporating multiple triggering mechanisms for the release of actives. J Microencapsul 1996 Sep–Oct; 13: 575–88
Leyden J, Grove GL. Randomized facial tolerability studies comparing gel formulations of retinoids used to treat acne vulgaris. Cutis 2001 Jun; 67(6 Suppl.): 17–27
Schafer-Korting M, Korting HC, Ponce-Poschl E. Liposomal tretinoin for uncomplicated acne vulgaris. Clin Investig 1994 Dec; 72: 1086–91
Schaller M, Steinle R, Korting HC. Light and electron microscopic findings in human epidermis reconstructed in vitro upon topical application of liposomal tretinoin. Acta Derm Venereol 1997 Mar; 77: 122–6
Worobec SM, Wong FGA, Tolman EL, et al. Percutaneous absorption of 3H-tretinoin in normal volunteers [abstract]. J Invest Dermatol 1991; 96: 574A
Franz TJ, Lehmann PA, Franz SF. Topical use of retinoic acid gel is not teratogenic [abstract]. J Invest Dermatol 1993; 100: 490A
Van Hoogdalem EJ, Baven TLM, Spiegel-Melsen I, et al. Transdermal absorption of Clindamycin and tretinoin from topically applied anti-acne formulations in man. Biopharm Drug Dispos 1998; 19: 563–9
Latriano L, Tzimas G, Wong F, et al. The percutaneous absorption of topically applied tretinoin and its effect on endogenous concentrations of tretinoin and its metabolites after single doses or long-term use. J Am Acad Dermatol 1997 Mar; 36(3 Pt 2): S37–46
Webster GF. Topical tretinoin in acne therapy. J Am Acad Dermatol 1998 Aug; 39(2 Pt 3): S38–44
Melnik B, Kinner T, Plewig G. Influence on oral Isotretinoin treatment on the composition of comedonal lipids. Implications for comedogenesis in acne vulgaris. Arch Dermatol Res 1988; 280: 97–102
Hirschel-Scholz S, Siegenthaler G, Saurat JH. Isotretinoin differs from other synthetic retinoids in its modulation of human cellular retinoic acid binding protein (CRABP). Br J Dermatol 1989 May; 120: 639–44
Sitzmann JH, Bauer FW, Cunliffe WJ, et al. In situ hybridization analysis of CRABP II expression in sebaceous follicles from 13-cis retinoic acid-treated acne patients. Br J Dermatol 1995 Aug; 133: 241–8
Tsukada M, Schroder M, Roos TC, et al. 13-cis retinoic acid exerts its specific activity on human sebocytes through selective intracellular isomerization to all-trans retinoic acid and binding to retinoid acid receptors. J Invest Dermatol 2000 Aug; 115: 321–7
Zouboulis CC. Exploration of retinoid activity and the role of inflammation in acne: issues affecting future directions for acne therapy. J Eur Acad Dermatol Venereol 2001; 15 Suppl. 3: 63–7
Vahlquist A, Rollman O, Holland DB, et al. Isotretinoin treatment of severe acne affects the endogenous concentrations of vitamin A in sebaceous glands. J Invest Dermatol 1990; 94: 496–8
Chen C, Jensen BK, Mistry G, et al. Negligible systemic absorption of topical Isotretinoin cream: implications for teratogenicity. J Clin Pharmacol 1997 Apr; 37: 279–84
Cunliffe WJ, Glass D, Goode K, et al. A double-blind investigation of the potential systemic absorption of Isotretinoin, when combined with chemical sunscreens, following topical application to patients with widespread acne of the face and trunk. Acta Derm Venereol 2001 Jan–Feb; 81: 14–7
Hughes BR, Norris JF, Cunliffe WJ. A double-blind evaluation of topical Isotretinoin 0.05%, benzoyl peroxide gel 5% and placebo in patients with acne. Clin Exp Dermatol 1992 May; 17: 165–8
Jensen BK, McGann LA, Kachevsky V, et al. The negligible systemic availability of retinoids with multiple and excessive topical application of Isotretinoin 0.05% gel (Isotrex) in patients with acne vulgaris. J Am Acad Dermatol 1991 Mar; 24: 425–8
Shroot B, Michel S. Pharmacology and chemistry of adapalene. J Am Acad Dermatol 1997 Jun; 36(6 Pt 2): S96–103
Jamoulle JC, Grandjean L, Lamaud E, et al. Follicular penetration and distribution of topically applied CD 271, a new naphthoic acid derivative intended for topical acne treatment. J Invest Dermatol 1990 May; 94: 731–2
Shroot B, Michel S, Allec J, et al. A new concept of drug delivery for acne. Dermatology 1998; 196: 165–70
Allec J, Chatelus A, Wagner N. Skin distribution and pharmaceutical aspects of adapalene gel. J Am Acad Dermatol 1997 Jun; 36(6 Pt 2): S119–25
Verschoore M, Langner A, Wolska H, et al. Efficacy and safety of CD 271 alcoholic gels in the topical treatment of acne vulgaris. Br J Dermatol 1991 Apr; 124: 368–71
Shalita A, Weiss JS, Chalker DK, et al. A comparison of the efficacy and safety of adapalene gel 0.1% and tretinoin gel 0.025% in the treatment of acne vulgaris: a multicenter trial. J Am Acad Dermatol 1996 Mar; 34: 482–5
Grosshans E, Marks R, Mascaro JM, et al. Evaluation of clinical efficacy and safety of adapalene 0.1% gel versus tretinoin 0.025% gel in the treatment of acne vulgaris, with particular reference to the onset of action and impact on quality of life. Br J Dermatol 1998 Oct; 139 Suppl. 52: 26–33
Cunliffe WJ, Poncet M, Loesche C, et al. A comparison of the efficacy and tolerability of adapalene 0.1 % gel versus tretinoin 0.025% gel in patients with acne vulgaris: a meta-analysis of five randomized trials. Br J Dermatol 1998 Oct; 139 Suppl. 52: 48–56
Michel S, Jomard A, Demarchez M. Pharmacology of adapalene. Br J Dermatol 1998 Oct; 139 Suppl. 52: 3–7
Cunliffe WJ, Caputo R, Dreno B, et al. Clinical efficacy and safety comparison of adapalene gel and tretinoin gel in the treatment of acne vulgaris: Europe and US multicenter trials. J Am Acad Dermatol 1997 Jun; 36(6 Pt 2): S126–34
Verschoore M, Bouclier M, Czernielewski J, et al. Topical retinoids: their uses in dermatology. Dermatol Clin 1993 Jan; 11: 107–15
Millikan LE. Adapalene: an update on newer comparative studies between the various retinoids. Int J Dermatol 2000 Oct; 39: 784–8
Brogden RN, Goa KE. Adapalene: a review of its pharmacological properties and clinical potential in the management of mild to moderate acne. Drugs 1997 Mar; 53: 511–9
Shroot B, Michel S. Pharmacology of retinoids in the skin: In vitro and in vivo assays. Eur J Med Chem 1995; 30 Suppl.: 487s–503s
Bernard BA. Adapalene, a new chemical entity with retinoid activity. Skin Pharmacol 1993; 6 Suppl. 1: 61–9
Griffiths CE, Ancian P, Humphries J, et al. Adapalene 0.1% gel and adapalene 0.1% cream stimulate retinoic acid receptor mediated gene transcription without significant irritative effects in the skin of healthy human volunteers. Br J Dermatol 1998 Oct; 139 Suppl. 52: 12–6
Martin B, Meunier C, Montels D, et al. Chemical stability of adapalene and tretinoin when combined with benzoyl peroxide in presence and in absence of visible light and ultraviolet radiation. Br J Dermatol 1998 Oct; 139 Suppl. 52: 8–11
Wolf JE. An update of recent clinical trials examining adapalene and acne. J Eur Acad Dermatol Venereol 2001; 15 Suppl. 3: 23–9
Foster RH, Brogden RN, Benfield P. Tazarotene. Drugs 1998 May; 55: 705–11
Schwarz EJ, Reginato MJ, Shao D, et al. Retinoic acid blocks adipogenesis by inhibiting C/EBPbeta-mediated transcription. Mol Cell Biol 1997 Mar; 17: 1552–61
Nagpal S, Patel S, Jacobe H, et al. Tazarotene-induced gene 2 (TIG2), a novel retinoid-responsive gene in skin. J Invest Dermatol 1997 Jul; 109: 91–5
Nagpal S, Patel S, Asano AT, et al. Tazarotene-induced gene 1 (TIG1), a novel retinoic acid receptor-responsive gene in skin. J Invest Dermatol 1996 Feb; 106: 269–74
DiSepio D, Ghosn C, Eckert RL, et al. Identification and characterization of a retinoid-induced class II tumor suppressor/growth regulatory gene. Proc Natl Acad Sci U S A 1998 Dec; 95: 14811–5
DiSepio D, Malhotra M, Chandraratna RA, et al. Retinoic acid receptor-nuclear factor-interleukin 6 antagonism: a novel mechanism of retinoid-dependent inhibition of a keratinocyte hyperproliferative differentiation marker. J Biol Chem 1997 Oct; 272: 25555–9
Shalita AR, Chalker DK, Griffith RF, et al. Tazarotene gel is safe and effective in the treatment of acne vulgaris: a multicenter, double-blind, vehicle-controlled study. Cutis 1999 Jun; 63: 349–54
Leyden J, Lowe N, Kakita L, et al. Comparison of treatment of acne vulgaris with alternate-day applications of tazarotene 0.1% gel and once-daily applications of adapalene 0.1% gel: a randomized trial. Cutis 2001 Jun; 67(6 Suppl.): 10–6
Kakita L. Tazarotene versus tretinoin or adapalene in the treatment of acne vulgaris. J Am Acad Dermatol 2000 Aug; 43(2 Pt 3): S51–4
Tang-Liu DD, Matsumoto RM, Usansky JI. Clinical pharmacokinetics and drug metabolism of tazarotene: a novel topical treatment for acne and psoriasis. Clin Pharmacokinet 1999 Oct; 37: 273–87
Marks R. Clinical safety of tazarotene in the treatment of plaque psoriasis. J Am Acad Dermatol 1997 Aug; 37(2 Pt 3): S25–32
Chandraratna RA. Tazarotene; first of a new generation of receptor-selective retinoids. Br J Dermatol 1996 Oct; 135 Suppl. 49: 18–25
Orfanos CE, Ehlert R, Gollnick H. The retinoids: a review of their clinical pharmacology and therapeutic use. Drugs 1987 Oct; 34: 459–503
Goswami BC, Baishya B, Baraa AB, et al. Topical retinoyl β-glucuronide is an effective treatment of mild to moderate acne vulgaris in Asian-Indian patients. Skin Pharmacol Appl Skin Physiol 1999; 12: 167–73
Gunning DB, Barua AB, Lloyd RA, et al. Retinoyl β-glucuronide: a nontoxic retinoid for the topical treatment of acne. J Dermatol Treat 1994; 5: 181–5
Barua AB, Olson JA. Percutaneous absorption, excretion and metabolism of all-trans retinoyl β-glucuronide and of all-trans retinoic acid in the rat. Skin Pharmacol 1996; 9: 17–26
Fort-Lacoste L, Verscheure Y, Tisne-Versailles J, et al. Comedolytic effect of topical retinaldehyde in the rhino mouse model. Dermatology 1999; 199 Suppl. 1: 33–5
Morel P, Vienne MP, Beylot C, et al. Clinical efficacy and safety of a topical combination of retinaldehyde 0.1% with erythromycin 4% in acne vulgaris. Clin Exp Dermatol 1999 Sep; 24: 354–7
Toyoda M, Morohashi M. An overview of topical antibiotics for acne treatment. Dermatology 1998; 196: 130–4
Strauss JS, Stranieri AM. Acne treatment with topical erythromycin and zinc: effect of Propionibacterium acnes and free fatty acid composition. J Am Acad Dermatol 1984 Jul; 11: 86–9
Puhvel SM. Effects of treatment with erythromycin 1.5 percent topical solution or Clindamycin phosphate 1.0 percent topical solution on P. acnes counts and free fatty acid levels. Cutis 1983 Mar; 31: 339–42
Cunliffe WJ. Topical erythromycin in clinical and laboratory studies. In: Mark SR, editor. Topical antibiotics in acne. London: Martin Dunitz, 1989: 127–36
Esterly NB, Furey NL. Acne: current concepts. Pediatrics 1978 Dec; 62: 1044–55
Leeming JP, Holland KT, Cunliffe WJ. The pathological and ecological significance of microorganisms colonizing acne vulgaris comedones. J Med Microbiol 1985 Aug; 20: 11–6
Eady EA, Cove JH. Topical antibiotic therapy: current status and future prospects. Drugs Exp Clin Res 1990; 16: 423–33
Schachner L, Pestana A, Kittles C. A clinical trial comparing the safety and efficacy of a topical erythromycin-zinc formulation with a topical Clindamycin formulation. J Am Acad Dermatol 1990 Mar; 22: 489–95
Plewig G, Kligman AM. Acne and rosacea. 2nd rev. ed. Berlin: Springer Verlag, 1993
Leyden JJ. Current issues in antimicrobial therapy for the treatment of acne. J Eur Acad Dermatol Venereol 2001; 15 Suppl. 3: 51–5
Kurokawa I, Nishijima S, Kawabata S. Antimicrobial susceptibility of Propionibacterium acnes isolated from acne vulgaris. Eur J Dermatol 1999 Jan–Feb; 9: 25–8
Eady EA, Farmery MR, Ross JI, et al. Effects of benzoyl peroxide and erythromycin alone and in combination against antibiotic-sensitive and -resistant skin bacteria from acne patients. Br J Dermatol 1994 Sep; 131: 331–6
Leyden J, Kaidbey K, Levy SF. The combination formulation of Clindamycin 1% plus benzoyl peroxide 5% versus 3 different formulations of topical Clindamycin alone in the reduction of Propionibacterium acnes: an in vivo comparative study. Am J Clin Dermatol 2001; 2: 263–6
Leyden JJ, Hickman JG, Jarratt MT, et al. The efficacy and safety of a combination benzoyl peroxide/clindamycin topical gel compared with benzoyl peroxide alone and a benzoyl peroxide/erythromycin combination product. J Cutan Med Surg 2001 Jan–Feb; 5: 37–42
Leyden J. Are 2 combined antimicrobial mechanisms better than 1 for the treatment of acne vulgaris?: clinical and antimicrobial results of a topical combination product containing 1 % Clindamycin and 5% benzoyl peroxide. Introduction. Cutis 2001 Feb; 67(2 Suppl.): 5–7
Tschen E. Potential role for a new combination topical therapy in treating mild to moderate acne vulgaris. Cutis 2001 Feb; 67(2 Suppl.): 25–7
Burkhart CN, Specht K, Neckers D. Synergistic activity of benzoyl peroxide and erythromycin. Skin Pharmacol Appl Skin Physiol 2000 Sep–Oct; 13: 292–6
Mesquita-Guimaraes J, Ramos S, Tavares MR, et al. A doubleblind clinical trial with a lotion containing 5% benzoyl peroxide and 2% miconazole in patients with acne vulgaris. Clin Exp Dermatol 1989 Sep; 14: 357–60
Webster G. Combination azelaic acid therapy for acne vulgaris. J Am Acad Dermatol 2000 Aug; 43(2 Pt 3): S47–50
Resh W, Stoughton RB. Topically applied antibiotics in acne vulgaris: clinical response and suppression of Corynebacterium acnes in open comedones. Arch Dermatol 1976 Feb; 112: 182–4
Stoughton RB, Resh W. Topical Clindamycin in the control of acne vulgaris. Cutis 1976 Mar; 17: 551–4
Gratton D, Raymond GP, Guertin-Larochelle S, et al. Topical Clindamycin versus systemic tetracycline in the treatment of acne: results of a multiclinic trial. J Am Acad Dermatol 1982 Jul; 7: 50–3
Becker LE, Bergstresser PR, Whiting DA, et al. Topical Clindamycin therapy for acne vulgaris: a cooperative clinical study. Arch Dermatol 1981 Aug; 117: 482–5
Stoughton RB, Cornell RC, Gange RW, et al. Double-blind comparison of topical 1 percent Clindamycin phosphate (Cleocin T) and oral tetracycline 500 mg/day in the treatment of acne vulgaris. Cutis 1980 Oct; 26: 424–5
Franz TJ. On the bioavailability of topical formulations of Clindamycin hydrochloride. J Am Acad Dermatol 1983 Jul; 9: 66–73
Milstone EB, McDonald AJ, Scholhamer Jr CF. Pseudomembranous colitis after topical application of Clindamycin. Arch Dermatol 1981 Mar; 117: 154–5
Parry MF, Rha CK. Pseudomembranous colitis caused by topical Clindamycin phosphate. Arch Dermatol 1986 May; 122: 583–4
Siegle RJ, Fekety R, Sarbone PD, et al. Effects of topical Clindamycin on intestinal microflora in patients with acne. J Am Acad Dermatol 1986 Aug; 15(2 Pt 1): 180–5
Rietschel RL, Duncan SH. Clindamycin phosphate used in combination with tretinoin in the treatment of acne. Int J Dermatol 1983 Jan–Feb; 22: 41–3
Barza M, Goldstein JA, Kane A, et al. Systemic absorption of Clindamycin hydrochloride after topical application. J Am Acad Dermatol 1982 Aug; 7: 208–14
Algra RJ, Rosen T, Waisman M. Topical Clindamycin in acne vulgaris: safety and stability. Arch Dermatol 1977 Oct; 113: 1390–1
Levy S. Dermatopharmacology of a new combination gel formulation for the topical treatment of acne. Cutis 2001 Feb; 67(2 Suppl.): 8–12
Lesher Jr JL, Chalker DK, Smith Jr JG, et al. An evaluation of a 2% erythromycin ointment in the topical therapy of acne vulgaris. J Am Acad Dermatol 1985 Mar; 12: 526–31
Bernstein JE, Shalita AR. Topically applied erythromycin in inflammatory acne vulgaris. J Am Acad Dermatol 1980 Apr; 2: 318–21
Fulton Jr JE, Pablo G. Topical antibacterial therapy for acne: study of the family of erythromycins. Arch Dermatol 1974 Jul; 110: 83–6
Puschmann M, Meyer-Rohn J. The efficacy of a topical preparation containing erythromycin in the treatment of acne. Dermatologica 1982 May; 164: 343–9
Schmidt JB, Knobler R, Neumann R, et al. External erythromycin therapy of acne [in German]. Z Hautkr 1983 Dec 15; 58: 1754–60
Fluhr JW, Bosch B, Gloor M, et al. In-vitro and in-vivo efficacy of zinc acetate against Propionibacteria alone and in combination with erythromycin. Zentralbl Bakteriol 1999 Oct; 289: 445–56
Bojar RA, Eady EA, Jones CE, et al. Inhibition of erythromycin-resistant Propionibacteria on the skin of acne patients by topical erythromycin with and without zinc. Br J Dermatol 1994 Mar; 130: 329–36
Pierard-Franchimont C, Goffin V, Visser JN, et al. A doubleblind controlled evaluation of the sebosuppressive activity of topical erythromycin-zinc complex. Eur J Clin Pharmacol 1995; 49: 57–60
Pierard GE, Pierard-Franchimont C. Effect of a topical erythromycin-zinc formulation on sebum delivery: evaluation by combined photometric-multi-step samplings with Sebutape. Clin Exp Dermatol 1993 Sep; 18: 410–3
Cochran RJ, Tucker SB, Flannigan SA. Topical zinc therapy for acne vulgaris. Int J Dermatol 1985 Apr; 24: 188–90
Van Hoogdalem EJ, Terpstra IJ, Baven AL. Evaluation of the effect of zinc acetate on the stratum corneum penetration kinetics of erythromycin in healthy male volunteers. Skin Pharmacol 1996; 9: 104–10
Anderson RL, Cook CH, Smith DE. The effect of oral and topical tetracycline on acne severity and on surface lipid composition. J Invest Dermatol 1976 Mar; 66: 172–7
Norris JF, Hughes BR, Basey AJ, et al. A comparison of the effectiveness of topical tetracycline, benzoyl-peroxide gel and oral Oxytetracycline in the treatment of acne. Clin Exp Dermatol 1991 Jan; 16: 31–3
Burton J. A placebo-controlled study to evaluate the efficacy of topical tetracycline and oral tetracycline in the treatment of mild to moderate acne. Dermatology Research Group. J Int Med Res 1990 Mar–Apr; 18: 94–103
Padilla RS, McCabe JM, Becker LE. Topical tetracycline hydrochloride vs. topical Clindamycin phosphate in the treatment of acne: a comparative study. Int J Dermatol 1981 Jul–Aug; 20: 445–8
Frank SB. Topical treatment of acne with a tetracycline preparations: results of a multi-group study. Cutis 1976 Mar; 17: 539–45
Gardner KJ, Cunliffe WJ, Eady EA, et al. Variation in comedonal antibiotic concentrations following application of topical tetracycline for acne vulgaris. Br J Dermatol 1994 Nov; 131: 649–54
Akamatsu H, Sasaki H, Kurokawa I, et al. Effect of nadifloxacin on neutrophil functions. J Int Med Res 1995 Jan–Feb; 23: 19–26
Ross JI, Snelling AM, Eady EA, et al. Phenotypic and genotypic characterization of antibiotic-resistant Propionibacterium acnes isolated from acne patients attending dermatology clinics in Europe, the USA, Japan and Australia. Br J Dermatol 2001 Feb; 144: 339–46
Kurokawa I, Nishijima S, Kawabata S. Antimicrobial susceptibility of Propionibacterium acnes isolated from acne vulgaris. Eur J Dermatol 1999 Jan–Feb; 9: 25–8
Nishijima S, Kurokawa I, Kawabata S. Sensitivity of Propionibacterium acnes isolated from acne patients: comparative study of antimicrobial agents. J Int Med Res 1996 Nov–Dec; 24: 473–7
Vogt K, Hahn H, Hermann J, et al. Antimicrobial evaluation of nadifloxacin (OPC-7251), a new topical quinolone, in acne vulgaris. Drugs 1995; 49 Suppl. 2: 266–8
Vogt K, Hermann J, Blume U, et al. Comparative activity of the topical quinolone OPC-7251 against bacteria associated with acne vulgaris. Eur J Clin Microbiol Infect Dis 1992 Oct; 11: 943–5
Oizumi N, Kawabata S, Hirao M, et al. Relationship between mutations in the DNA gyrase and topoisomerase IV genes and nadifloxacin resistance in clinically isolated quinolone-resistant Staphylococcus aureus. J Infect Chemother 2001 Sep; 7: 191–4
Takei M, Fukuda H, Kishii R, et al. Target preference of 15 quinolones against Staphylococcus aureus, based on antibacterial activities and target inhibition. Antimicrob Agents Chemother 2001 Dec; 45: 3544–7
Fluhr JW, Gloor M, Merkel W, et al. Antibacterial and sebosuppressive efficacy of a combination of chloramphenicol and pale sulfonated shale oil. Multicentre, randomized, vehiclecontrolled, double-blind study on 91 acne patients with acne papulopustulosa (Plewig and Kligman’s grade II–III). Arzneimittel Forschung 1998 Feb; 48: 188–96
Abeck D, Mempel N. Antibiotika. In: Korting HC, Sterry W, editors. Therapeutische Verfahren in der Dermatologie. Dermatika und Kosmetika. Berlin: Blackwell, 2001: 295–305
Gollnick H. The treatment of acne. Drugs Today 1992; 28: 353–61
Puschmann M. Clinico-experimental studies on the effect of benzoylperoxide [in German]. Hautarzt 1982 May; 33: 257–65
Tschen EH, Katz HI, Jones TM, et al. A combination benzoyl peroxide and Clindamycin topical gel compared with benzoyl peroxide, Clindamycin phosphate, and vehicle in the treatment of acne vulgaris. Cutis 2001 Feb; 67: 165–9
Vermeulen B, Remon JP, Nelis H. The formulation and stability of erythromycin-benzoyl peroxide in a topical gel. Int J Pharm 1999 Feb 1; 178: 137–41
Hegemann L, Toso SM, Kitay K, et al. Anti-inflammatory actions of benzoyl peroxide: effects on the generation of reactive oxygen species by leucocytes and the activity of protein kinase C and calmodulin. Br J Dermatol 1994 May; 130: 569–75
Cunliffe WJ, Stainton C, Forster RA. Topical benzoyl peroxide increases the sebum excretion rate in patients with acne. Br J Dermatol 1983 Nov; 109: 577–9
Cotterill JA. Benzoyl peroxide. Acta Derm Venereol Suppl (Stockh) 1980; Suppl. 89: 57–63
Fyrand O, Jakobsen HB. Water-based versus alcohol-based benzoyl peroxide preparations in the treatment of acne vulgaris. Dermatologica 1986; 172: 263–7
Mills Jr OH, Kligman AM, Pochi P, et al. Comparing 2.5%, 5%, and 10% benzoyl peroxide on inflammatory acne vulgaris. Int J Dermatol 1986 Dec; 25: 664–7
Morsches B, Holzmann H. Studies on the percutaneous absorption of benzoyl peroxide [in German]. Arzneimittel Forschung 1982; 32: 298–300
Ellis CN, Leyden J, Katz HI, et al. Therapeutic studies with a new combination benzoyl peroxide/clindamycin topical gel in acne vulgaris. Cutis 2001 Feb; 67(2 Suppl.): 13–20
Lookingbill DP, Chalker DK, Lindholm JS, et al. Treatment of acne with a combination clindamycin/benzoyl peroxide gel compared with Clindamycin gel, benzoyl peroxide gel and vehicle gel: combined results of two double-blind investigations. J Am Acad Dermatol 1997 Oct; 37: 590–5
Harkaway KS, McGinley KJ, Foglia AN, et al. Antibiotic resistance patterns in coagulase-negative staphylococci after treatment with topical erythromycin, benzoyl peroxide, and combination therapy. Br J Dermatol 1992 Jun; 126: 586–90
Tucker SB, Tausend R, CochranR, et al. Comparison of topical Clindamycin phosphate, benzoyl peroxide, and a combination of the two for the treatment of acne vulgaris. Br J Dermatol 1984 Apr; 110: 487–92
Chalker DK, Shalita A, Smith Jr JG, et al. A double-blind study of the effectiveness of a 3% erythromycin and 5% benzoyl peroxide combination in the treatment of acne vulgaris. J Am Acad Dermatol 1983 Dec; 9: 933–6
Nazzaro-Porro M, Passi S, Picardo M, etal. Beneficial effect of 15% azelaic acid cream on acne vulgaris. Br J Dermatol 1983 Jul; 109: 45–8
Graupe K, Cunliffe WJ, Gollnick HP, et al. Efficacy and safety of topical azelaic acid (20 percent cream): an overview of results from European clinical trials and experimental reports. Cutis 1996 Jan; 57(1 Suppl.): 20–35
Gollnick H, Graupe K, Detmar M, et al. Azelainsäure für die Behandlung der Akne: Pharmakologie, in-vitro- und in-vivo-Effekte sowie klinische Ergebnisse und Toleranz. Z Hautkr 1992; 67: 975–87
Cavicchini S, Caputo R. Long-term treatment of acne with 20% azelaic acid cream. Acta Derm Venereol Suppl (Stockh) 1989; 143: 40–4
Katsambas A, Graupe K, Stratigos J. Clinical studies of 20% azelaic acid cream in the treatment of acne vulgaris: comparison with vehicle and topical tretinoin. Acta Derm Venereol Suppl (Stockh) 1989; 143: 35–9
Akamatsu H, Komura J, Asada Y, et al. Inhibitory effect of azelaic acid on neutrophil functions: a possible cause for its efficacy in treating pathogenetically unrelated diseases. Arch Dermatol Res 1991; 283: 162–6
Passi S, Picardo M, Zompetta C, et al. The oxyradical-scavenging activity of azelaic acid in biological systems. Free Radic Res Commun 1991; 15: 17–28
Gollnick H. Azelainsäure. In: Korting HC, Sterry W, editors. Therapeutische Verfahren in der Dermatologie. Dermatika und Kosmetika. Berlin: Blackwell, 2001: 253–64
Mayer-da-Silva A, Gollnick H, Detmar M, et al. Effects of azelaic acid on sebaceous gland, sebum excretion rate and keratinization pattern in human skin: an in vivo and in vitro study. Acta Derm Venereol Suppl (Stockh) 1989; 143: 20–30
Cunliffe WJ, Holland KT. Clinical and laboratory studies on treatment with 20% azelaic acid cream for acne. Acta Derm Venereol Suppl (Stockh) 1989; 143: 31–4
Bladon PT, Burke BM, Cunliffe WJ, et al. Topical azelaic acid and the treatment of acne: a clinical and laboratory comparison with oral tetracycline. Br J Dermatol 1986 Apr; 114: 493–9
Fitton A, Goa KL. Azelaic acid: a review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders. Drugs 1991 May; 41: 780–98
Passi S, Picardo M, Nazzaro-Porro M, et al. Antimitochondrial effect of saturated medium chain length (C8-C13) dicarboxylic acids. Biochem Pharmacol 1984 Jan 1; 33: 103–8
Bojar RA, Cutcliffe AG, Graupe K, et al. Follicular concentrations of azelaic acid after a single topical application. Br J Dermatol 1993 Oct; 129: 399–402
Tauber U, Weiss C, Matthes H. Percutaneous absorption of azelaic acid in humans. Exp Dermatol 1992 Nov; 1: 176–9
Zander E, Weisman S. Treatment of acne vulgaris with salicylic acid pads. Clin Ther 1992 Mar–Apr; 14: 247–53
Schmidt-Wendtner M-H. Salizylsäure. In: Korting HC, Sterry W, editors. Therapeutische Verfahren in der Dermatologie. Dermatika und Kosmetika. Berlin: Blackwell, 2001: 203–7
Proudfoot AT. Toxicity of salicylates. Am J Med 1983 Nov 14; 75: 99–103
Davies MG, Briffa DV, Greaves MW. Systemic toxicity from topically applied salicylic acid. BMJ 1979; 1: 661–5
Rosenfield RL. Pilosebaceous physiology in relation to hirsutism and acne. Clin Endocrinol Metab 1986 May; 15: 341–62
Lucky AW. Topical antiandrogens: what use in dermatology? Arch Dermatol 1985 Jan; 121: 55–6
Lookingbill DP, Abrams BB, Ellis CN, et al. Inocoterone and acne: the effect of a topical antiandrogen: results of a multicenter clinical trial. Arch Dermatol 1992 Sep; 128: 1197–200
Gruber DM, Sator MO, Joura EA, et al. Topical cyproterone acetate treatment in women with acne: a placebo-controlled trial. Arch Dermatol 1998 Apr; 134: 459–63
Messina M, Manieri C, Musso MC, Pastorino R. Oral and topical Spironolactone therapies in skin androgenization. Panminerva Med 1990 Apr–Jun; 32: 49–55
Shaw JC. Spironolactone in dermatologic therapy. J Am Acad Dermatol 1991 Feb; 24(2 Pt 1): 236–43
Gomez F, Ramelet AA, Ruedi B, et al. Lack of effect of a spironolactone-containing cream on hair growth in hirsute women. Dermatologica 1987; 174: 102–3
Chen W, Zouboulis CC, Fritsch M, et al. Evidence of heterogeneity and quantitative differences of the type 1 5α-reductase expression in cultured human skin cells: evidence of its presence in melanocytes. J Invest Dermatol 1998 Jan; 110: 84–9
Chen W, Zouboulis CC, Orfanos CE. The 5 alpha-reductase system and its inhibitors. Recent development and its perspective in treating androgen-dependent skin disorders. Dermatology 1996; 193: 177–84
Tung RC, Bergfeld WF, Vidimos AT, Remzi BK. α-Hydroxy acid-based cosmetic procedures: guidelines for patient management. Am J Clin Dermatol 2000 Mar–Apr; 1: 81–8
Van Scott EJ, Yu RJ. Hyperkeratinization, corneocyte cohesion, and alpha hydroxy acids. J Am Acad Dermatol 1984 Nov; 11(5 Pt 1): 867–79
Bershad SV. The modern age of acne therapy: a review of current treatment options. Mt Sinai J Med 2001 Sep–Oct; 68: 279–86
Mills Jr OH, Kligman AM. Is sulphur helpful or harmful in acne vulgaris? Br J Dermatol 1972 Jun; 86: 620–7
Mills Jr OH, Kligman AM. Assay of comedolytic activity in acne patients. Acta Derm Venereol 1983; 63: 68–71
Ernst E, Huntley A. Tea tree oil: a systematic review of randomized clinical trials. Forsch Komplementarmed Klass Naturheilkd 2000 Feb; 7: 17–20
Bassett IB, Pannowitz DL, Barnetson RS. A comparative study of tea-tree oil versus benzoylperoxide in the treatment of acne. Med J Aust 1990 Oct 15; 153: 455–8
Gollnick H, Cunliffe W, Berson D, et al. Global alliance to improve outcomes in acne. J Am Acad Dermatol 2003; 49 Suppl. 1: S1–37
Patel VB, Misra A, Marfatia YS. Topical liposomal gel of tretinoin for the treatment of acne: research and clinical implications. Pharm Dev Technol 2000; 5: 455–64
Honzak L, Sentjurc M. Development of liposome encapsulated Clindamycin for treatment of acne vulgaris. Pflugers Arch 2000; 440(5 Suppl.): R44–5
Nyirady J, Nighland M, Payonk G, et al. A comparative evaluation of tretinoin gel microsphere, 0.1%, versus tretinoin cream, 0.025%, in reducing facial shine. Cutis 2000 Aug; 66: 153–6
Galvin SA, Gilbert R, Baker M, et al. Comparative tolerance of adapalene 0.1% gel and six different tretinoin formulations. Br J Dermatol 1998 Oct; 139 Suppl. 52: 34–40
Rolland A, Wagner N, Chatelus A, et al. Site-specific drug delivery to pilosebaceous structures using polymeric microspheres. Pharm Res 1993 Dec; 10: 1738–44
Acknowledgements
Professor Gollnick has performed clinical studies with the following companies: Schering, Galderma, Hermal and Hoffmann-La Roche. The authors have provided no information on sources of funding.
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Krautheim, A., Gollnick, H. Transdermal Penetration of Topical Drugs Used in the Treatment of Acne. Clin Pharmacokinet 42, 1287–1304 (2003). https://doi.org/10.2165/00003088-200342140-00005
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DOI: https://doi.org/10.2165/00003088-200342140-00005