Summary
Drug absorption from the gastrointestinal (GI) tract and the impact of GI surgery and disease on drug absorption are discussed. Recommendations are made to manage problems of drug malabsorption. Absorption from the GI tract is a first-order process described by its rate and extent.
GI surgery changes the anatomy of the GI tract and alters important variables in the absorption process. In the wake of procedures which diminish small bowel surface area, the extent of absorption of phenytoin, digoxin, cyclosporin, aciclovir, hydrochlorothiazide and certain oral contraceptives is reported to be reduced. The underlying cause of the reduction is unknown. When gastric emptying time or pH are altered by surgery, the rate of drug absorption appears to be reduced. However, it is not clear which variable is more important in determining therapeutic effects.
The effects of coeliac and inflammatory bowel diseases on the distribution and clearance of drugs must be considered before attributing abnormal serum concentrations of drugs to malabsorption. GI disease may slow gastric emptying and delay the complete absorption of drugs when their rate of absorption depends on gastric emptying time. Other inflammatory GI diseases such as graft-versus-host disease (GVHD) of the gut, Behçet’s syndrome and scleroderma involving the GI tract may directly reduce absorption of drugs such as cyclosporin, amitriptyline, benzodiazepines, anticonvulsants, paracetamol (acetaminophen) and penicillamine. GI diseases which alter gut pH affect the absorption only of drugs with limited water solubility and pH-dependent dissolution such as ketoconazole.
Clinicians should be aware of the variable absorption seen after GI disease and surgery and monitor their patients accordingly.
Similar content being viewed by others
References
Ammitzboll T, Hendel L, Kreuzig F, Asboe-Hansen G. Bioavailability of D-penicillamine in relation to gastrointestinal involvement of generalized scleroderma. Scandinavian Journal of Rheumatology 16: 121–126, 1987
Atkinson K, Britton K, Paull P, Farrell C, Concannon A, et al. Detrimental effect of intestinal disease on absorption of orally administered cyclosporin. Transplantation Proceedings 15 (Suppl. 1): 2446–2449, 1983
Backman L, Beerman B, Groschinsky-Grind, Hallberg D. Malabsorption of hydrochlorothiazide following intestinal shunt surgery. Clinical Pharmacokinetics 4: 63–68, 1979
Banker GS, Sharma VE. Advances in controlled gastrointestinal absorption. In Prescott & Nimmo (Eds) Drug absorption: Proceedings of the Edinburgh International Conference, pp. 194–204, ADIS Press, Auckland, 1979
Beermann B, Hellstrom K, Rosen A. The absorption of orally administered 12 alpha-3H digoxin in man. Clinical Science 43: 507–518, 1972
Beerman B, Hellstrom K, Rosen A. The gastrointestinal absorption of digoxin in seven patients with gastric or small intestinal reconstructions. Acta Medica Scandinavica 193: 293–297, 1973
Benn A, Cooke WT. Intraluminal pH of duodenum and jejunum in fasting subjects with normal and abnormal gastric or pancreatic function. Scandinavian Journal of Gastroenterology 6: 313–317, 1971
Bennett WM. Guide to drug dosage in renal failure. Clinical Pharmacokinetics 15: 326–354, 1988
Bergan T, Bjerke PEM, Fausa O. Pharmacokinetics of metronidazole in patients with enteric disease compared to normal volunteers. Chemotherapy 27: 233–238, 1981
Bergan T, Lolekha S, Cheong MK, Poh CL, Patancharoen S. Consequences of diarrhoeal disease on the pharmacokinetics of norfloxacin. Scandinavian Journal of Infectious Diseases (Suppl. 56): 11–13, 1988
Blanchard J. Gastrointestinal absorption II: formulation factors affecting drug bioavailability. American Journal of Pharmacy 150: 132–151, 1978
Breckenridge A, Orme M. Kinetics of warfarin absorption in man. Clinical Pharmacology and Therapeutics 14: 955–961, 1973
Broyles JE, Brown RO, Self T, Fredrick RC, Luther RW. Nortriptyline absorption in short bowel syndrome. Journal of Parenteral and Enterai Nutrition 14: 326–327, 1990
Buchwald H. True informed consent in surgical treatment of morbid obesity: the current case for both jejunoileal and gastric bypass. American Journal of Clinical Nutrition 33: 482–494, 1980
Buckler KG. Effects of gastric surgery upon gastric emptying in cases of peptic ulceration. Gut 8: 137–147, 1967
Calvo R, Sarabia S, Carlos R, Du Souich P. Sulfamethazine absorption and disposition: effect of surgical procedures for gastrointestinal ulcers. Biopharmaceutics and Drug Disposition 8: 115–124, 1987
Carlson JA, Mann HJ, Canafax DM. Effect of pH on disintegration and dissolution of ketoconazole tablets. American Journal of Hospital Pharmacy 40: 1334–1336, 1983
Chaleby K, El-Yazigi A, Atiyeh M. Decreased drug absorption in a patient with Behçet’s syndrome. Clinical Chemistry 33: 1679–1681, 1987
Cooke AR. Control of gastric emptying and motility. Gastroenterology 68: 804–816, 1975
Cooperman AM, Cook SA. Gastric emptying — physiology and measurements. Surgery Clinics of North America 56: 1277–1287, 1976
Davis SS, Hardy JG, Fara J. Transit of pharmaceutical dosage forms through the small intestine. Gut 27: 886–892, 1986
Dean P, Joshi S, Kaminski DL. Long term outcome of reversal of small intestinal bypass operations. American Journal of Surgery 159: 118–124, 1990
Deykin D. Warfarin therapy. New England Journal of Medicine 283: 691–694, 801–803, 1970
Doherty JE, Marcus FI, Binnion PF. A multicenter evaluation of the absolute bioavailability of digoxin dosage forms. Current Therapeutic Research 35: 301–306, 1984
Drew RH, Perfect JR, Gallis HA. Use of fluconazole with documented malabsorption of ketoconazole. Clinical Pharmacy 7: 622–623, 1988
Dudley HAF, Gillanders LA. Barium-meal examination following Billroth-I gastrectomy. British Journal of Surgery 53: 403–407, 1966
Dworkin B, Wormser GP, Rosenthal WS, Heier SK, Braunstein M, et al. Gastrointestinal manifestations of the acquired immunodeficiency syndrome: a review of 22 cases. American Journal of Gastroenterology 80: 774–778, 1985
Elliot PR, Powell-Tuck J, Gillespie PE, Laidlow JM, Lennard-Jones JE, et al. Prednisolone absorption in acute colitis. Gut 21: 49–51, 1980
Evard D, Aubry JP, LeQuintrec Y, Cheymol G, Cheymol A. Study of the bioavailability of pindolol in malabsorption syndromes. British Journal of Clinical Pharmacology 18: 632–637, 1984
Frazer AC. Disordered gastro-intestinal function and its relationship to tropical sprue, coeliac disease and idiopathic steatorrhoea. Transactions of the Royal Society of Tropical Medicine and Hygiene 46: 576–585, 1952
Freed E, Atkinson K, Biggs J. Failed amitriptyline absorption. Medical Journal of Australia 140: 509–510, 1984
Gerson DG, Lowe EH, Lindenbaum J. Bioavailability of digoxin tablets in patients with gastrointestinal dysfunction. American Journal of Medicine 69: 43–49, 1980
Gibaldi M. Limitations of classical theories of drug absorption. In Prescott & Nimmo (Eds) Drug absorption: Proceedings of the Edinburgh International Conference, pp. 1–5, ADIS Press, Auckland, 1979
Grevel J. Absorption of cyclosporin A after oral dosing. Transplant Proceedings 18 (Suppl. 5): 9–15, 1986
Grevel J, Nuesch E, Abisch E, Kutz K. Pharmacokinetics of oral cyclosporin A in healthy subjects. European Journal of Clinical Pharmacology 31: 211–216, 1986
Gridelli B, Scanlon L, Pellicci R, LaPointe R, DeWolf A, et al. Cyclosporin metabolism and pharmacokinetics following intravenous and oral administration in the dog. Transplantation 41: 388–391, 1986
Grimmer SFM, Back DJ, Orme MLE, Cowie A, Gilmore I, et al. The bioavailability of ethinyloestradiol and levonorgestrel in patients with an ileostomy. Contraception 33: 51–59, 1986
Gubbins PO, Bertch KE. Drug absorption in gastrointestinal disease and surgery. Pharmacotherapy 9: 285–295, 1989
Hall WH, Doherty JE. Titrated digoxin XVI: gastric absorption. American Journal of Digestive Diseases 16: 903–908, 1971
Hall WH, Doherty JE, Gammill J, Sherwood J. Tritiated digoxin (XXII): absorption and excretion in malabsorption syndromes. American Journal of Medicine 56: 437–442, 1974
Heading RC, Nimmo J, Prescott LF, Tothill P. The dependence of paracetamol absorption on the rate of gastric emptying. British Journal of Pharmacology 47: 415–421, 1973
Heizer WD, Pittman AW, Hammond JE, Fitch DD, Bustrack JA, et al. Absorption of digoxin from tablets and capsules in subjects with malabsorption syndromes. DICP: Annals of Pharmacotherapy 23: 764–749, 1989
Heizer WD, Smith TW, Goldfinger SE. Absorption of digoxin in patients with malabsorption syndromes. New England Journal of Medicine 285: 257–259, 1971
Hogben CAM, Schenker LS, Tocco DJ, Brodie BB. Absorption of drugs from the stomach II: the human. Journal of Pharmacology and Experimental Therapeutics 120: 540–545, 1957
Holt S, Heading RC, Clements JA, Tothill P, Prescott LF. Acetaminophen absorption and metabolism in celiac disease and Crohn’s disease. Clinical Pharmacology and Therapeutics 30: 232–238, 1981
Johansen K, Eriksson M, Olsson-Liljequist B, Stintzing G. Absorption of erythromycin in children with gluten intolerance. Acta Paediatrica Scandinavica 78: 959–960, 1989
Jung D, Powell JR, Walson P, Perrier D. Effect of dose on phenytoin absorption. Clinical Pharmacology and Therapeutics 28: 479–85, 1980
Jusko WJ, Conti DR, Molson A, Kuritzky P, Giller J, et al. Digoxin absorption from tablets and elixir: the effect of radiation-induced malabsorption. Journal of the American Medical Association 230: 1554–1555, 1974
Jusko WJ, Rose JQ. Monitoring prednisone and prednisolone. Therapeutic Drug Monitoring 2: 169–179, 1980
Kaniwa N, Aoyagi N, Ogata H, Ejima A. Gastric emptying rates of drug preparations: I. Effects of size of dosage forms, food and species on gastric emptying rates. Journal of Pharmacobio-Dynamics 11: 563–570, 1988a
Kaniwa N, Aoyagi N, Ogata H, Ejima A. Gastric emptying rates of drug preparations: II. Effects of size and density of enteric-coated drug preparations and food on gastric emptying rates in humans. Journal of Pharmacobio-Dynamics 11: 571–575, 1988b
Kaplan SA. Absorption screening and new drug development. In Prescot t & Nimmo (Eds) Drug absorption: Proceedings of the Edinburgh International Conference, pp. 144–156, ADIS Press, Auckland, 1979
Kearns PJ, O’Reilly RA. Bioavailability of warfarin in a patient with severe short bowel syndrome. Journal of the American Society for Parenteral and Enterai Nutrition 10: 100–101, 1986
Kennedy MC, Wade DN. Phenytoin absorption in patients with ileojejunal bypass. British Journal of Clinical Pharmacology 7: 515–518, 1979
Kitis G, Lucas ML, Bishop H, Sargent A, Schneider RE, et al. Altered jejunal surface pH in coeliac disease: its effect on propranolol and folic acid absorption. Clinical Science 63: 373–380, 1982
Knight GC, Macris MP, Peric M, Duncan JM, Frazier OH, et al. Cyclosporin A pharmacokinetics in a cardiac allograft recipient with jejunoileal bypass. Transplant Proceedings 20: 351–355, 1988
Kotier DP, Gaetz HP, Lange M, Klein EB, Holt PR. Enteropathy associated with AIDS. Annals of Internal Medicine 101: 421–428, 1984
Koup JR, Gibaldi M. Some comments on the evaluation of bioavailability data. Drug Intelligence and Clinical Pharmacy 24: 327–330, 1980
Kozower M, Veatch L, Kaplan MM. Decreased clearance of prednisolone, a factor in the development of corticosteroid side effects. Journal of Clinical Endocrinology and Metabolism 38: 407–412, 1974
Krammer PA, Chapron DJ, Benson J, Mercik SA. Tetracycline absorption in elderly patients with achlorhydria. Clinical Pharmacology and Therapeutics 23: 467–472, 1978
Krausz MM, Berry E, Freund U. Absorption of orally administered digoxin after massive resection of the small bowel. American Journal of Gastroenterology 71: 220–223, 1979
Lake-Bakaar G, Quadros E, Beidas S, Elsakr M, Winston T, et al. Gastric secretory failure in patients with the acquired immunodeficiency syndrome (AIDS). Annals of Internal Medicine 109: 502–504, 1988b
Lake-Bakaar G, Winston T, Lake-Bakaar D, Gupta N, Beidas S, et al. Gastropathy and ketoconazole malabsorption in the acquired immunodeficiency syndrome (AIDS). Annals of Internal Medicine 109: 471–473, 1988a
Lehman ME, Kolb KW, Barnhart GR, Wagman LD, Barr WH. Warfarin absorption in a patient with short-bowel syndrome. Clinical Pharmacy 4: 325–326, 1985
Levy RH, Bauer LA. Basic pharmacokinetics. Therapeutic Drug Monitoring 8: 47–58, 1986
Lewis GP, Jusko WJ, Burke CW, Groves L. The Boston Collaborative Drug Surveillance Program: prednisolone side-effects and serum protein levels. Lancet 2: 779–781, 1971
Lucas ML, Cooper BT, Lei FH, Johnson IT, Holmes GKT, et al. Acid microclimate in coeliac and Crohn’s disease: a model for folate malabsorption. Gut 19: 735–742, 1978
Marcus FI, Quinn EJ, Horton H, Jacobs S, Pippin S, et al. The effect of jejunoileal bypass on the pharmacokinetics of digoxin in man. Circulation 55: 537–41, 1977
Melander A, Kahlmeter G, Kamme C, Ursing B. Bioavailability of metronidazole in fasting and nonfasting healthy subjects and in patients with Crohn’s Disease. European Journal of Clinical Pharmacology 12: 69–72, 1977
Mindel A, Carney O. Acyclovir malabsorption. British Medical Journal 296: 1605, 1988
Milsap RL, George DE, Szefler SJ, Murray KA, Lebenthal E, et al. Effect of inflammatory bowel disease on absorption and disposition of prednisolone. Digestive Diseases and Sciences 28: 161–168, 1983
Mitchell JF, Maas LC, Barger RC, Gelzayd EA. Successful oral anticoagulant therapy in a patient with short bowel syndrome. American Journal of Hospital Pharmacy 34: 171–172, 1977
Moberg S, Carlberger G. Gastric emptying in healthy subjects and in patients with various malabsorptive states. Scandinavian Journal of Gastroenterology 9: 17–21, 1974
Nilsson LO, Victor A, Kral JG, Johansson EDB, Kock NG. Absorption of an oral contraceptive gesten in ulcerative colitis before and after proctocolectomy and construction of a continent ileostomy. Contraception 31: 195–204, 1985
Nimmo WS. Drugs, diseases, and altered gastric emptying. Clinical Pharmacokinetics 1: 189–203, 1976
Nimmo WS. Gastric emptying and drug absorption. In Prescott & Nimmo (Eds) Drug absorption: Proceedings of the Edinburgh International Conference, pp. 11–20, ADIS Press, Auckland, 1979
Nimmo WS. Gastric emptying and anaesthesia. Canadian Journal of Anaesthesia 36: S45–47, 1989
Ochs HR, Bodem G, Schaffer PK, Kodrat G, Dengler HJ. Absorption of digoxin from the distal parts of the intestine in man. European Journal of Clinical Pharmacology 9: 95–7, 1975
Ochs HR, Greenblatt DJ, Allen MD, Harmatz JS, Shader RI, et al. Effect of age and Billroth gastrectomy on absorption of desmethyl-diazepam from clorazepate. Clinical Pharmacology and Therapeutics 26: 449–456, 1979
Ochs HR, Greenblatt DJ, Dengler HJ. Absorption of oral tetracycline in patients with Billroth II gastrectomy. Journal of Pharmacokinetics and Biopharmaceutics 6: 295–303, 1978
Ochs HR, Otten H, Greenblatt DJ, Dengler HJ. Diazepam absorption: effects of age, sex and Billroth gastrectomy. Digestive Diseases and Sciences 27: 225–230, 1982
Parsons RL. Drug absorption in gastrointestinal disease with particular reference to malabsorption syndromes. Clinical Pharmacokinetics 2: 45–60, 1977
Parsons RL, Hossak G, Paddock G. The absorption of antibiotics in adult patients with coeliac disease. Journal of Antimicrobial Chemotherapy 1: 39–50, 1975
Parsons RL, Jusko WJ, Young JM. Pharmacokinetics of antibiotic absorption in coeliac disease. Journal of Antimicrobial Chemotherapy 2: 214–215, 1976a
Parsons RL, Kaye CM, Raymond K. Pharmacokinetics of salicylate and indomethacin in coeliac disease. European Journal of Clinical Pharmacology 11: 473–477, 1977
Parsons RL, Kaye CM, Raymond K, Trounce JR, Turner P. Absorption of propranolol and practolol in coeliac disease. Gut 17: 139–143, 1976b
Payne JH, DeWind LT. Surgical treatment of obesity. American Journal of Surgery 118: 141–147, 1969
Peterson DI. Phenytoin absorption following jejunoileal bypass. Bulletin of Clinical Neurosciences 48: 148–149, 1983
Ptachcinski RJ, Venkataramanan R, Rosenthal JT, Burckart GJ, Taylor RJ, et al. The effect of food on cyclosporin absorption. Transplantation 40: 174–176, 1985
Rankine DA, Sadler RM. Phenytoin suspension: ‘not shaken, not stirred’. Canadian Journal of Neurological Sciences 15: 240, 1988
Rankine DA, Sadler RM. Phenytoin suspension. Neurology 39: 1644, 1989
Rinder HM, Murphy JW, Higgins GL. Impact of unusual gastrointestinal problems on the treatment of tricyclic antidepressant overdose. Annals of Emergency Medicine 17: 1079–1081, 1988
Roberts R, Sketris IS, Abraham I, Givner ML, MacDonald AS. Cyclosporin absorption in two patients with short-bowel syndrome. Drug Intelligence and Clinical Pharmacy 22: 570–572, 1988
Robinson DH, Narducci WA, Ueda CT. Drug delivery and administration. In Dipiro et al. (Eds) Pharmacotherapy: a pathophysiologic approach, pp. 15–34, Elsevier Science Publishing Co, Amsterdam, 1989.
Rowland M, Tozer TN. Extravascular dose. In Rowland & Tozer (Eds) Clinical pharmacokinetics: concepts and applications, 2nd ed., pp. 33–48, Lea & Febiger, Philadelphia, 1989a
Rowland M, Tozer TN. Movement through membranes. In Rowland & Tozer (Eds) Clinical pharmacokinetics: concepts and applications, 2nd ed., pp. 108–110, Lea & Febiger, Philadelphia, 1989b
Sandle GI, Ward A, Rawlins MD, Record CO. Propranolol absorption in untreated coeliac disease. Clinical Science 63: 81–85, 1982
Sarkar MA, Garnett WR, Karnes T. The effects of storage and shaking on the settling properties of phenytoin suspension. Neurology 39: 207–209, 1989
Sawyers JL. Management of postgastrectomy syndromes. American Journal of Surgery 159: 8–14, 1990
Schneider RE, Babb J, Hilary B, Mitchard M, Hoare AM, et al. Plasma levels of propranolol in treated patients with coeliac disease and patients with Crohn’s disease. British Medical Journal 2: 794–795, 1976
Schultz NJ. Principles of drug therapy. Journal of Enterostomal Therapy 14: 212–215, 1987
Scott HW, Dean R, Shull JH, Abram HS, Webb W, et al. New considerations in the use of jejunoileal bypass in patients with morbid obesity. Annals of Surgery 177: 723–737, 1973
Secor JW, Schenker S. Drug metabolism in patients with liver disease. Advances in Internal Medicine 32: 379–406, 1987
Shaffer JL, Kershaw A, Houston JB. Disposition of metronidazole and its effects on sulphasalazine metabolism in patients with inflammatory bowel disease. British Journal of Clinical Pharmacology 21: 431–435, 1986
Shaffer JL, Williams SE, Turnberg LA, Houston JB, Rowland M. Absorption of prednisolone in patients with Crohn’s disease. Gut 24: 182–186, 1983
Shand DG. Presystemic hepatic metabolism: practical and pathophysiological aspects. In Prescott & Nimmo (Eds) Drug absorption: Proceedings of the Edinburgh International Conference, pp. 100–107, ADIS Press, Auckland, 1979
Shanker LS, Shore PA, Brodie BB, Hogben CAM. Absorption of drugs from the stomach I: the rat. Journal of Pharmacology and Experimental Therapeutics 120: 528–539, 1957
Tanner AR, Halliday JW, Powell LW. Serum prednisolone levels in Crohn’s disease and celiac disease following oral prednisolone administration. Digestion 21: 310–315, 1981
Terry SI, Gould JC, McManus JPA, Prescott LF. Absorption of penicillin and paracetamol after intestinal bypass surgery. European Journal of Clinical Pharmacology 23: 245–248, 1982
Ueda CT, Lemaire M, Gsell G, Misslin P, Nussbaumer K. Apparent dose-dependent oral absorption of cyclosporin A in rats. Biopharmaceutics and Drug Disposition 5: 141–151, 1984
Ueda CT, Lemaire M, Gsell G, Nussbaumer K. Intestinal lymphatic absorption of cyclosporin A following oral administration in an olive oil solution in rats. Biopharmaceutics and Drug Disposition 4: 113–124, 1983
VanDerMeer JWM, Keuning JJ, Scheijgrond HW, Heykants J, Van Cutsem J, et al. The influence of gastric acidity on the bioavailability of ketoconazole. Journal of Antimicrobial Chemotherapy 6: 552–554, 1980
Venho VMK, Aukee S, Jussila J, Mattila MJ. Effect of gastric surgery on the gastrointestinal drug absorption in man. Scandinavian Journal of Gastroenterology 10: 43–47, 1975
Venkataramanan R, Starzl TE, Yang S, Burckart GJ, Ptachcinski RJ, et al. Biliary excretion of cyclosporin in liver transplant patients. Transplant Proceedings 17: 286–289, 1985
Vetticaden SJ, Lehman ME, Barnhart GR, Barr WH. Digoxin absorption in a patient with short bowel syndrome. Clinical Pharmacy 5: 62–64, 1986
Victor A, Odlind V, Kral JG. Oral contraceptive absorption and sex hormone binding globulins in obese women: effects of jejunoileal bypass. Gastroenterology Clinics of North America 16: 483–491, 1987
Welling PG, Tse FLS. Factors contributing to variability in drug pharmacokinetics I: absorption. Journal of Clinical Hospital Pharmacy 9: 163–179, 1984
Winter ME, Tozer TN. Phenytoin. In Evans et al. (Eds) Applied pharmacokinetics: principles of therapeutic drug monitoring, 2nd ed., pp. 493–539, Applied Therapeutics Inc., Spokane, 1986
Wright HK, Olson MD. Short bowel syndrome. Current Problems in Surgery 3: 51, 1971
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gubbins, P.O., Bertch, K.E. Drug Absorption in Gastrointestinal Disease and Surgery. Clin. Pharmacokinet. 21, 431–447 (1991). https://doi.org/10.2165/00003088-199121060-00004
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003088-199121060-00004