Skip to main content
SpringerLink
Log in

Single-Dose Pharmacokinetics of Rifapentine in Women

  • Published:
Journal of Pharmacokinetics and Biopharmaceutics Aims and scope Submit manuscript

Abstract

Gender can be an important variable in the absorption and disposition of some drugs. In this open-label study, 15 healthy, nonsmoking women received a single 600-mg oral dose of rifapentine. Plasma samples were obtained at frequent intervals for up to 72 hr after the dose to determine the pharmacokinetic (PK) parameters of rifapentine and its active metabolite, 25-desacetyl-rifapentine. Peak plasma rifapentine concentrations (Cmax ) were observed 5.9 hr after ingestion of the single dose. The mean area under the rifapentine plasma concentration–time curve [AUC(0 → ∞ )] was 325 μg · hr ml and the mean elimination half-life (t1/2 ) was 16.3 hr. Plasma concentrations for the 25-desacetyl metabolite peaked at 15.4 hr after the rifapentine dose and declined with a terminal half-life of 17.3 hr. These rifapentine and 25-desacetyl-rifapentine PK data in women were compared to data generated previously in healthy men. Striking similarities in the PK profiles of parent drug and metabolite were found in the two populations. Mean differences in rifapentine CL/F (12%) and t1/2 (2%) were small. The only adverse event reported in the female subjects was discoloration of the urine. Based on these PK and safety data, no dosage adjustments for rifapentine based on gender are recommended.

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. L. B. Heifets, P. J. Lindholm-Levy, and M. A. Flory. Bactericidal activity in vitro of various rifamycins against M. avium and M. tuberculosis. Am. Rev. Resp. Dis. 141:626–630 (1990).

    Article  CAS  PubMed  Google Scholar 

  4. N. Mor, B. Simon, N. Mezo, and L. Heifets. Comparison of activities of rifapentine and rifampin against Mycobacterium tuberculosis residing in human macrophages. Antimicrob. Agents Chemother. 39:2073–2077 (1995).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. 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. (submitted for publication).

  6. 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).

    Article  CAS  PubMed  Google Scholar 

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

    Google Scholar 

  8. 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]. Pharm. Res. 12(Suppl.): S419 (1995).

    Google Scholar 

  9. Y. Biya, N. Xikuam, Z. Lizhen, and Z. Fengying. Absorption and elimination of cyclopentyl-rifamycin in human subjects. Chinese J. Tuberc. Resp. Dis. 10:267–268 (1987).

    Google Scholar 

  10. S. L. Chan, W. W. Yew, J. H. D. Porter, K. P. W. J. McAdam, B. W. Allen, and J. M. Dickinson. Comparison of Chinese and Western rifapentines and improvement of bioavailability by prior taking of various meals. Int. J. Antimicrob. Agents 3:267–274 (1994).

    Article  CAS  PubMed  Google Scholar 

  11. Z. Qing, C. Yijan, and Z. Yingyuan. Clinical pharmacokinetic study on rifapentine. Chinese J. Antibiot. 19:456–458 (1994).

    Google Scholar 

  12. C. Zheng, L. Yi, and Z. Huiyan. Pharmacokinetics of domestic rifapentine in patients with acute pulmonary infections. Chinese J. Antibiot. 12:333–336 (1987).

    Google Scholar 

  13. A. Keung, M. G. Eller, K. A. McKenzie, and S. J. Weir. Single and multiple dose pharmacokinetics of rifapentine and its active metabolite 25-desacetyl-rifapentine in man. Pharmacol. Ther. (submitted for publication).

  14. J. C. Bennet. Inclusion of women in clinical trials: Policies for population subgroups. Int. J. Tuber. Lung Dis. 329:288–292 (1993).

    Google Scholar 

  15. R. B. Merkatz, R. Temple, S. Sobel, K. Feiden, and D. A. Kessler. Women in clinical trials of new drugs. A change in Food and Drug Administration policy. New Engl. J. Med. 329:292–296 (1993).

    Article  CAS  PubMed  Google Scholar 

  16. C. V. Fletcher, E. P. Acosta, and J. M. Strykowski. Gender differences in human pharmacokinetics and pharmacodynamics. J. Adolescent Health 15:619–629 (1994).

    Article  CAS  Google Scholar 

  17. C. H. Gleiter and U. Gundert-Remy. Gender differences in pharmacokinetics. Eur. J. Drug Metab. Pharmacokin. 21:123–128 (1996).

    Article  CAS  Google Scholar 

  18. R. Z. Harris, L. Z. Benet, and J. B. Schwartz. Gender effects in pharmacokinetics and pharmacodynamics. Drugs 50:222–239 (1995).

    Article  CAS  PubMed  Google Scholar 

  19. K. A. Yonkers, J. C. Kando, J. O. Cole, and S. Blumenthal. Gender differences in pharmacokinetics and pharmacodynamics of psychotropic medication. Am. J. Psychiat. 149:587–595 (1992).

    Article  CAS  PubMed  Google Scholar 

  20. J. C. Kando, K. A. Yonkers, and J. O. Cole. Gender as a risk factor for adverse events to medications. Drugs 50:1–6 (1995).

    Article  CAS  PubMed  Google Scholar 

  21. American College of Clinical Pharmacy. ACCP White paper: Women as research subjects. Pharmacotherapy 13:534–542 (1993).

    Google Scholar 

  22. R. Scotti. Sex differences in blood levels of some antibiotics. Chemotherapy 18:205–211 (1973).

    Article  CAS  PubMed  Google Scholar 

  23. H. Iwainsky, K. Winsel, E. Werner, and H. Eule. On the pharmacokinetics of rifampicin during treatment with intermittent administration. II. Influence of age and sex of the patients. Scand. J. Resp. Dis. 57:5–11 (1976).

    CAS  Google Scholar 

  24. L. Verbist. Rifampicin blood levels in man. Acta Tuberc. Pneumol. Belg. 60:288–298 (1969).

    CAS  PubMed  Google Scholar 

  25. M. D. Holland. Rifampicin—what dose for pulmonary tuberculosis? South Afr. Med. J. 46:604–608 (1972).

    CAS  Google Scholar 

  26. D. C. Colborn, R. C. Li, and P. K. Narang. Influence of gender on rifabutin (R) kinetics [abstr.]. Clin. Pharmacol. Ther. 53:182 (1993).

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  28. L. Verbist. Pharmacological study of rifampicin after repeated high dosage during intermittent combined therapy. I. Variation of the rifampicin serum levels. Respiration 28(Suppl. 7):7–16 (1971).

    Article  PubMed  Google Scholar 

  29. T. F. Blaschke and M. H. Skinner. The clinical pharmacokinetics of rifabutin. Clin. Infect. Dis. 22(Suppl. 1):S15–S22 (1996).

    Article  CAS  PubMed  Google Scholar 

  30. G. Cocchiara, M. Strolin Benedetti, G. P. Vicario, M. Ballabio, B. Gioia, S. Viogglio, and A. Vigevani. Urinary metabolites of rifabutin, a new antimycobacterial agent, in human volunteers. Xenobiotica 19:769–780 (1989).

    Article  CAS  PubMed  Google Scholar 

  31. E. Iatsimirskaia, S. Tulebaev, E. Storozhuk, I. Utkin, D. Smith, N. Gerber, and T. Koudriakova. Metabolism of rifabutin in human enterocyte and liver microsomes: Kinetic parameters, identification of enzyme systems, and drug interactions with macrolides and antifungal agents. Clin. Pharmacol. Ther. 61:554–562 (1997).

    Article  CAS  PubMed  Google Scholar 

  32. C. B. Trapnell, C. Jamis-Dow, R. W. Klecker, and J. M. Collins. Metabolism of rifabutin and its 25-desacetyl metabolite, LM565, by human liver microsomes and recombinant human cytochrome P-450 3A4: Relevance to clinical interaction with fluconazole. Antimicrob. Agents Chemother. 41:924–926 (1997).

    CAS  PubMed Central  PubMed  Google Scholar 

  33. R. Battaglia, E. Pianezzola, G. Salgarollo, G. Zini, and M. S. Benedetti. Absorption, disposition and preliminary metabolic pathway of 14C-rifabutin in animals and man. J. Antimicrob. Chemother. 26:813–822 (1990).

    Article  CAS  PubMed  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 Women. J Pharmacokinet Pharmacodyn 26, 75–85 (1998). https://doi.org/10.1023/A:1023276808298

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1023276808298

Search

Navigation