Abstract | OBJECTIVE: 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:
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Authors | Alina S Bergshoeff, Tom F W Wolfs, Sibyl P M Geelen, David M Burger |
Journal | The Annals of pharmacotherapy
(Ann Pharmacother)
Vol. 37
Issue 4
Pg. 521-5
(Apr 2003)
ISSN: 1060-0280 [Print] United States |
PMID | 12659608
(Publication Type: Case Reports, Journal Article)
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Chemical References |
- Anti-HIV Agents
- Antitubercular Agents
- RNA, Viral
- Nelfinavir
- Ritonavir
- Rifampin
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Topics |
- Anti-HIV Agents
(blood, metabolism, pharmacokinetics, therapeutic use)
- Antitubercular Agents
(therapeutic use)
- Area Under Curve
- Drug Interactions
- HIV
- HIV Infections
- Humans
- Infant
- Male
- Mycobacterium tuberculosis
- Nelfinavir
(analogs & derivatives, blood, pharmacokinetics, therapeutic use)
- RNA, Viral
- Rifampin
(adverse effects, pharmacology, therapeutic use)
- Ritonavir
(pharmacology, therapeutic use)
- Tuberculosis, Pulmonary
(drug therapy)
- Viral Load
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