QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Résumé Extracto Full Text PDF Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Articles Ahead of Print [Order Reprint] Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bergshoeff, A. S Articles by Burger, D. M Search for Related Content PubMed PubMed Citation Articles by Bergshoeff, A. S Articles by Burger, D. M

Ritonavir-Enhanced Pharmacokinetics of Nelfinavir/M8 During Rifampin Use

Research Pharmacologist, Department of Clinical Pharmacy, University Medical Center, Nijmegen, Netherlands

Tom FW Wolfs, MD PhD

Pediatrician, University Medical Center/Wilhelmina Children's Hospital, Department of Infectious Diseases, Utrecht, Netherlands

Sibyl PM Geelen, MD PhD

Pediatrician, University Medical Center/Wilhelmina Children's Hospital, Department of Infectious Diseases

David M Burger, PharmD PhD

Assistant Professor of Clinical Pharmacology/Hospital Pharmacist, Department of Clinical Pharmacy, University Medical Center, Nijmegen

Reprints: Alina S Bergshoeff PharmD, Department of Clinical Pharmacy, University Medical Center, P.O. Box 9101, 533 KF, 6500 HB Nijmegen, Netherlands, FAX 31 24 3540331, E-mail A.Bergshoeff{at}akf.umcn.nl

OBJECTIVE: To describe a case of successful protease inhibitor–based highly active antiretroviral therapy (HAART) concomitant with rifampin.

CASE SUMMARY: In a 7-month-old male infant with tuberculosis and HIV-1 infection, tuberculosis therapy including rifampin and HAART containing the protease inhibitor nelfinavir 40 mg/kg every 8 hours was started. Intensive steady-state pharmacokinetic sampling from baseline to 8 hours revealed very low plasma concentrations of nelfinavir: area under the plasma concentration–time curve (AUC_0-24) <10% of adult population values for 750 mg every 8 hours and nonquantifiable concentrations of nelfinavir's principal metabolite (M8). Nelfinavir 40 mg/kg every 8 hours was then substituted with nelfinavir 30 mg/kg twice daily plus ritonavir 400 mg/m² twice daily. Intensive steady-state (0–12 h) pharmacokinetic sampling was repeated. Nelfinavir concentrations had improved, but remained low when compared with adult population values of 1250 mg every 12 hours: AUC_0-24 21.9 versus 47.6 mg/L•h (46%) and 12-hour trough level (C₁₂) 0.25 versus 0.85 mg/L (29%). However, concentrations of M8 considerably exceeded population values: AUC_0-24 57.5 versus 13.6 mg/L•h (443%) and C₁₂ 1.35 versus 0.28 mg/L (482%). Since M8 concentrations were highly elevated, pharmacokinetic parameters for (nelfinavir + M8) were used rather than those for nelfinavir alone. Thus, AUC_0-24 (nelfinavir + M8) and C₁₂ (nelfinavir + M8) comprised 130% and 142%, respectively of the adult population values. This, in addition to good clinical response and tolerability, favored continuation of the regimen.

CONCLUSIONS: In an infant, nelfinavir-containing HAART was successfully used with rifampin after the addition of ritonavir. Ritonavir resolved the pharmacokinetic interaction between rifampin and nelfinavir by boosting nelfinavir and, especially, M8 concentrations. More research is needed to confirm these results.

Key Words: nelfinavir, pharmacokinetics, rifampin

Published Online, February 28, 2003. www.theannals.com, DOI 10.1345/aph.1C335

This article has been cited by other articles:

				D. M. Burger, S. Agarwala, M. Child, A. Been-Tiktak, Y. Wang, and R. Bertz Effect of rifampin on steady-state pharmacokinetics of atazanavir with ritonavir in healthy volunteers. Antimicrob. Agents Chemother., October 1, 2006; 50(10): 3336 - 3342. [Abstract] [Full Text] [PDF]

				V. N. Hirani, J. L. Raucy, and J. M. Lasker CONVERSION OF THE HIV PROTEASE INHIBITOR NELFINAVIR TO A BIOACTIVE METABOLITE BY HUMAN LIVER CYP2C19 Drug Metab. Dispos., December 1, 2004; 32(12): 1462 - 1467. [Abstract] [Full Text] [PDF]