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Effect of efavirenz on the pharmacokinetics of ketoconazole in HIV-infected patients

  • Pharmacokinetics and Disposition
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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

To investigate the effect of efavirenz on the ketoconazole pharmacokinetics in HIV-infected patients.

Methods

Twelve HIV-infected patients were assigned into a one-sequence, two-period pharmacokinetic interaction study. In phase one, the patients received 400 mg of ketoconazole as a single oral dose on day 1; in phase two, they received 600 mg of efavirenz once daily in combination with 150 mg of lamivudine and 30 or 40 mg of stavudine twice daily on days 2 to 16. On day 16, 400 mg of ketoconazole was added to the regimen as a single oral dose. Ketoconazole pharmacokinetics were studied on days 1 and 16.

Results

Pretreatment with efavirenz significantly increased the clearance of ketoconazole by 201%. Cmax and AUC0−24 were significantly decreased by 44 and 72%, respectively. The T ½ was significantly shorter by 58%.

Conclusion

Efavirenz has a strong inducing effect on the metabolism of ketoconazole.

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References

  1. Department of Health and Human Services (2006) Guidelines for the Use of Antiretroviral Agents in HIV-1-infected Adults and Adolescents-October 10, 2006. http://www.aidsinfo.nih.gov. Assessed December 20, 2006

  2. Heel RC, Brogden RN, Carmine A, Morley PA, Speight TM, Avery GS (1982) Ketoconazole: a review of its therapeutic efficacy in superficial and systemic fungal infections. Drugs 23:1–36

    PubMed  CAS  Google Scholar 

  3. Adkins JC, Noble S (1998) Efavirenz. Drugs 56:1055–1064

    Article  PubMed  CAS  Google Scholar 

  4. Yuen KH, Peh KK (1998) Simple high-performance liquid chromatographic method for determination of ketoconazole in human ploasma. J Chromatogr B 715:436–440

    Article  CAS  Google Scholar 

  5. Ellepola AN, Samaranayake LP (2000) Oral candidal infections and antimycotics. Crit Rev Oral Biol Med 11:172–198

    Article  PubMed  CAS  Google Scholar 

  6. Thai Ministry of Public Health (2002) National guidelines for the clinical management of HIV infection in children and adults, 7th edn. Garnsadsana, Bangkok

  7. Teanpaisan R, Nittayananta W, Chongsuvivatwong V (2000) Biotypes of oral Candida albicans isolated from AIDS patients and HIV-free subjects in Thailand. J Oral Pathol Med 29:193–199

    Article  PubMed  CAS  Google Scholar 

  8. Van Roey J, Haxaire M, Kamya M, Lwanga I, Katabira E (2004) Comparative efficacy of topical therapy with a slow-release mucoadhesive buccal tablet containing miconazole nitrate versus systemic therapy with ketoconazole in HIV-positive patients with oropharyngeal candidiasis. J Acquir Immune Defic Syndr 35:144–150

    Article  PubMed  Google Scholar 

  9. Gascoigne EW, Barton GJ, Michaels M, Meuldermans WH (1981) The kinetics of ketoconazole in animals and man. Clin Res Rev 1:177–187

    CAS  Google Scholar 

  10. Brass C, Galgiani JN, Blaschke TF, Defelice R, O’Reilly RA, Stevens DA (1982) Disposition of ketoconazole, an oral antifungal, in human. Antimicrob Agents Chemother 21:151–158

    PubMed  CAS  Google Scholar 

  11. Lamson M, Robinson P, Gigliotti M, Myers WM (1998) The pharmacokinetic interaction of nevirapine and ketoconazole. In: Abstr 12th World AIDS Conf, abstr 12218. Geneva, p 55

  12. Berry M, Mulcahy F, Merry C, Gibbons S, Back D (1999) Pharmacokinetics and potential interactions and amongst antiretroviral agents used to treat HIV infection. Clin Pharmacokinet 36:289–304

    Article  Google Scholar 

  13. Clarke SM, Mulcahy FM, Tjia J, Reynolds HE, Gibbon SE, Berry MG, Back DJ (2001) The pharmacokinetics of methadone in HIV-positive patients receiving the non-nucleoside reverse transcriptase inhibitor efavirenz. Br J Clin Pharmacol 51:213–217

    Article  PubMed  CAS  Google Scholar 

  14. Aarnoutse RE, Grintjes K, Telgt DS, Stek M Jr, Hugen PW, Reiss P, Koopmans PP, Hekster YA, Burger DM (2002) The influence of efavirenz on the pharmacokinetics of a twice-daily combination of indinavir and low-dose ritonavir in healthy volunteers. Clin Pharmacol Ther 71:57–67

    Article  PubMed  CAS  Google Scholar 

  15. Dailly E, Allavena C, Raffi F, Jolliet P (2005) Pharmacokinetic evidence of the induction of lopinavir metabolism by efavirenz. Br J Clin Pharmacol 60:32–34

    Article  PubMed  CAS  Google Scholar 

  16. Gerber JG, Rosenkranz SL, Fichtenbaum CJ, Vega JM, Yang A, Alston BL, Brobst SW, Segal Y, Aberg JA (2005) Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and pravastatin: results of AIDS Clinical Trials Group 5108 Study. J Acquir Immune Defic Syndr 39:307–312

    Article  PubMed  CAS  Google Scholar 

  17. Berruet N, Sentenac S, Auchere D, Gimenez F, Farinotti R, Fernandez C (2005) Effect of efavirenz on intestinal p-glycoprotein and hepatic p450 function in rats. J Pharm Pharmaceut Sci 8:226–234

    CAS  Google Scholar 

  18. Mouly S, Lown KS, Kornhauser D, Joseph JL, Fiske WD, Benedek IH, Watkin PB (2002) Hepatic but not intestinal CYP3A4 displays dose-dependent induction by efavirenz in human. Clin Pharmacol Ther 72:1–9

    Article  PubMed  CAS  Google Scholar 

  19. Wang EJ, Lew K, Casciano CN, Clement RP, Johnson WW (2002) Interaction of Common Azole Antifungals with P-glycoprotein. Antimicrob Agents Chemother 46:160–165

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We acknowledge and appreciate the financial support of this study by the Prince of Songkla University and would like to thank to Miss Stefania Vignotto and Mr. David Brown for checking our English. The experiments comply with the current laws of the country in which we were performed.

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Correspondence to Somchai Sriwiriyajan.

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Sriwiriyajan, S., Mahatthanatrakul, W., Ridtitid, W. et al. Effect of efavirenz on the pharmacokinetics of ketoconazole in HIV-infected patients. Eur J Clin Pharmacol 63, 479–483 (2007). https://doi.org/10.1007/s00228-007-0282-8

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  • DOI: https://doi.org/10.1007/s00228-007-0282-8

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