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  • Title: Ritonavir-enhanced pharmacokinetics of nelfinavir/M8 during rifampin use.
    Author: Bergshoeff AS, Wolfs TF, Geelen SP, Burger DM.
    Journal: Ann Pharmacother; 2003 Apr; 37(4):521-5. PubMed ID: 12659608.
    Abstract:
    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/m(2) 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 (C(12)) 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 C(12) 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 C(12) (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.
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