Skip to main content
SpringerLink
Log in

Single-dose Pharmacokinetics of Rifapentine in Elderly Men

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose. This study was undertaken to characterize the pharmacokinetic profiles of rifapentine and its active metabolite, 25-desacetyl-rifapentine, in elderly men.

Methods. Fourteen healthy, nonsmoking male volunteers between the ages of 65 and 82 years received a single oral 600 mg dose of rifapentine. Plasma samples were collected at frequent intervals for up to 72 hours postdose. The control group consisted of 20 healthy, young (18−45 years) male volunteers from a previous, single-dose (600 mg) rifapentine pharmacokinetic study.

Results. Plasma rifapentine concentrations above the minimum inhibitory concentration for M. tuberculosiswere observed at 2 hours after dosing. Disposition of rifapentine was monophasic with a mean terminal half-life of 19.6 hours. The peak plasma concentration of 25-desacetyl-rifapentine was found 21.7 hours, on average, after the rifapentine dose; the mean 25-desacetyl-rifapentine t1/2was 22.9 hours. Compared to the younger subjects, apparent oral clearance of rifapentine (24%) was lower in the elderly male (p < 0.05), and Cmax (28%) was higher. The only adverse event reported in both the older and younger subjects in these single-dose studies was discoloration of the urine.

Conclusions. Because the age-related changes in the pharmacokinetic profile of rifapentine observed in this study were modest and unlikely to be associated with toxicity, no dosage adjustments for this antibiotic are recommended in elderly patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. C. Truffot, R. Bismuth, and C. Boval. The in vitroand in vivoexperimental activity of cyclopentyl rifamycin (DL473) on Mycobacterium tuberculosis. Current Chemotherapy and Immunotherapy, Proceedings of the 12thInternational Congress of Chemotherapy. Florence, Italy, July 19–24, 1981. Abstract 693.

    Google Scholar 

  2. L. B. Heifets, P. J. Lindholm-Levy, and M. A. Flory. Bactericidal activity in vitroof various rifamycins against M. aviumand M. tuberculosis. Am. Rev. Respir. Dis. 141:626-630 (1990).

    PubMed  Google Scholar 

  3. J. M. Dickinson and D. A. Mitchison. In vitro activity of selected rifamycins against rifampicin-resistant M. tuberculosisand MAIS-complex mycobacteria. Tubercle. 68:177-182 (1987).

    PubMed  Google Scholar 

  4. W. Wehrli. Rifampin: mechanisms of action and resistance. Rev. Infect. Dis. 5(suppl 3):S407-S411 (1983).

    PubMed  Google Scholar 

  5. F-J. Leinweber. Possible physiological roles of carboxylic ester hydrolases. Drug Metab. Rev. 18:379-439 (1987).

    PubMed  Google Scholar 

  6. K. Reith, A. Keung, P. C. Toren, M. G. Eller, L. Cheng, and S. J. Weir. Mass balance and metabolism of 14C-rifapentine in healthy volunteers. Drug Metab. Dispos.(Accepted for publication).

  7. A. C. F. Keung, T. D. Miller, V. I. Green, M. Ames, M. G. Eller, and S. J. Weir. Bioavailability (BA) and food effect study of rifapentine in healthy adults [Abstract S-8372]. Pharm. Res. 12(suppl):S419 (1995).

    Google Scholar 

  8. A. T. Birmingham, A. J. Coleman, M. L. E. Orme, B. K. Park, N. J. Pearson, A. H. Short, and P. J. Southgate. Antibacterial activity in serum and urine following oral administration in man of DL473 (a cyclopentyl derivative of rifampicin). Br. J. Clin. Pharmacol. 6:455P-456P (1978).

    PubMed  Google Scholar 

  9. G. Buniva, D. Sassella, and G. M. Frigo. Pharmacokinetics of rifapentine in man. Proc. Int. Congr. Chemother. 111:29-33 (1983).

    Google Scholar 

  10. G. Acocella. Clinical pharmacokinetics of rifampicin. Clin. Pharmacokinet. 3:108-127 (1978).

    PubMed  Google Scholar 

  11. S. Dawling and P. Crome. Clinical pharmacokinetic considerations in the elderly: an update. Clin. Pharmacokinet. 17:236-263 (1989).

    PubMed  Google Scholar 

  12. W. A. Ritschel. Identification of populations at risk in drug testing and therapy: application to elderly patients. Eur. J. Drug Metab. Pharmacokinet. 18:101-111 (1993).

    PubMed  Google Scholar 

  13. G. Tsujimoto, K. Hashimoto, and B. B. Hoffman. Pharmacokinetic and pharmacodynamic principles of drug therapy in old age. Part 1. Int. J. Clin. Pharmacol. Ther. Toxicol. 27:13-26 (1989).

    PubMed  Google Scholar 

  14. K. W. Woodhouse. Pharmacokinetics of drugs in the elderly. J. Royal Soc. Med. 87(suppl 23):2-4 (1994).

    Google Scholar 

  15. M. A. Evans, E. J. Triggs, M. Cheung, G. A. Broe, and H. Creasey. Gastric emptying rate in the elderly: implications for drug therapy. J. Am. Geriatr. Soc. 29:201-205 (1981).

    PubMed  Google Scholar 

  16. G. B. Forbes and J. C. Reina. Adult lean body mass declines with age: some longitudinal observations. Metabolism 19:653-663 (1970).

    PubMed  Google Scholar 

  17. M. C. Geokas and B. J. Haverback. The ageing gastrointestinal tract. Am. J. Surg. 117:881-892 (1969).

    PubMed  Google Scholar 

  18. L. P. Novak. Aging, total body potassium, fat-free mass, and cell mass in males and females between ages 18 and 85 years. J. Gerentol. 27:438-443 (1972).

    Google Scholar 

  19. C. Durnas, C-M. Loi, and B. J. Cusack. Hepatic drug metabolism and aging. Clin. Pharmacokinet. 19:359-389 (1990).

    PubMed  Google Scholar 

  20. D. S. Chutka, J. M. Evans, K. C. Fleming, and K. G. Mikkelson. Drug prescribing for elderly patients. Mayo Clin. Proc. 70:685-693 (1995).

    PubMed  Google Scholar 

  21. H. L. Rieder. Epidemiology of tuberculosis in Europe. Eur. Respir. J. 8(suppl 20):620s-632s (1995).

    Google Scholar 

  22. W. W. Stead and A. K. Dutt. Tuberculosis in the elderly. Semin. Respir. Infect. 4:189-197 (1989).

    PubMed  Google Scholar 

  23. C. R. Horsburgh, Jr. Epidemiology of Mycobacterium aviumComplex disease. Am. J. Med. 102(5C):11-15 (1997).

    Google Scholar 

  24. F. Varga and E. Fischer. Age-dependent changes in blood supply of the liver and in the biliary excretion of eosin in rats. In: K. Kitani, ed. Liver and ageing. Elsevier-North, Amsterdam, 1978, pp. 327-340.

    Google Scholar 

  25. K. Kitani, S. Kanai, P. Miura, Y. Morita, and M. Kisahara. The effect of aging on the biliary excretion of ouabain in the rat. Exper. Gerontol. 13:9-17 (1978).

    Google Scholar 

  26. T. F. Blaschke and M. H. Skinner. The clinical pharmacokinetics of rifabutin. Clin. Infect. Dis. 22(suppl 1):S15-22 (1996).

    PubMed  Google Scholar 

  27. A. Walubo, K. Chan, J. Woo, H. S. Chan. and C. L. Wong. The disposition of antituberculous drugs in plasma of elderly patients. II. Isoniazid, rifampicin and pyrazinamide. Meth. Find. Exp. Clin. Pharmacol. 13:551-556 (1991).

    Google Scholar 

  28. C. Advenier, C. Gobert, G. Houin, D. Bidet, S. Richelet, and J. P. Tillement. Pharmacokinetic studies of rifampicin in the elderly. Ther. Drug. Monitor. 5:61-65 (1983).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. North America Pharmacokinetics, Hoechst Marion Roussel, Inc., Marion Park Drive, Kansas City, Missouri, 64134

    Anther C. F. Keung, Mark G. Eller & Scott J. Weir

Authors
  1. Anther C. F. Keung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark G. Eller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Scott J. Weir
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Keung, A.C.F., Eller, M.G. & Weir, S.J. Single-dose Pharmacokinetics of Rifapentine in Elderly Men. Pharm Res 15, 1286–1291 (1998). https://doi.org/10.1023/A:1011960428896

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1011960428896

Search

Navigation