Abstract
Objectives: The study describes the pharmacokineties (PK) of the protease inhibitor nelfinavir and its active metabolite M8 in children and evaluates the influence of patient-related factors on nelfinavir plasma levels.
Methods: HIV-1-infected children treated with nelfinavir every 8 h (q8h) were eligible for inclusion in this retrospective study. 0-8 h intensive plasma pharmacokinetics (PK) sampling was performed at steady state. Nelfinavir maximum concentration (C-max), area under the plasma concentration-time curve in 0-8 h (AUC(0-8)), trough level at the 8 h time point (C-8) and relative apparent oral clearance (Cl*F/kg) were calculated.
Results: Twenty-four children (median age: 4.5 years, median nelfinavir dose: 28 mg/kg q8h) were included. Nelfinavir PK were highly variable: 10/24 children had an AUC(0-8) below the value of 12.5 mg/l*h, which has previously been associated with an increased virological failure rate in children. With children aged 0.69 mg/l predicted an AUC(0-8) >12.5 mg/l*h with 71% sensitivity and 80% specificity. Dose of nelfinavir per body surface area was a better predictor of AUC(0-8) than dose per body weight.
Conclusion: Nelfinavir PK show high interindividual variability in children. Children
| Original language | English |
|---|---|
| Pages (from-to) | 215-222 |
| Number of pages | 8 |
| Journal | Antiviral therapy |
| Volume | 8 |
| Issue number | 3 |
| Publication status | Published - Jun-2003 |
Keywords
- IMMUNODEFICIENCY-VIRUS TYPE-1
- REVERSE-TRANSCRIPTASE INHIBITORS
- HIV-PROTEASE INHIBITORS
- ANTIRETROVIRAL THERAPY
- PLASMA-CONCENTRATIONS
- VIROLOGICAL RESPONSE
- INFECTED CHILDREN
- TRIPLE THERAPY
- P-GLYCOPROTEIN
- EFAVIRENZ