|
|
Abstract
Nelfinavir (NFV) pharmacokinetics (PK) in HIV infected children: who are at risk for subtherapeutic plasma levels?
A S Bergshoeff1, P L A Fraaij2, T F W Wolfs3, S P M Geelen3, R de Groot2, D M Burger1
1University Medical Centre, Nijmegen, The Netherlands; 2University Hospital Rotterdam/Sophia Children's Hospital, Rotterdam, The Netherlands; 3Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands
Background
High interindividual variability in PK of protease inhibitors (PI) in children may put them at increased risk for subtherapeutic drug levels. We aimed to describe the PK of the PI NFV and its active metabolite M8 in children. Particular attention was paid to children below 2 years old, since very sparse PK data for this group are available. Factors related with subtherapeutic plasma levels of NFV were evaluated.
Methods
HIV infected children treated with NFV q8h + 2 nucleoside analogues were elegible for inclusion. 0-8h PK sampling was performed at steady-state. Plasma concentrations of NFV and M8 were analysed by HPLC. NFV peak plasma level (Cmax), area under the curve (AUC0-8), plasma trough level (Cmin) and oral clearance (Cl/kg) were calculated. NFV AUC0-8 < 12.5 mg/L*h was considered subtherapeutic.
Results
24 children were included (median age (IQR) 4.5 (0.71-7.1) yrs.). They received a median NFV dose of 28 (IQR 26-31) mg/kg q8h. PK data for NFV (median (IQR)) are shown below.
| overall (n=24) | age < 2 yr. (n=7) | age > 2 yr. (n=17) | | AUC0-8 (mg/L*h) | 13.1 (8.8-20.2) | 11.2 (8.9-20.8) | 15.0 (7.9-20.1) | | Cmax (mg/L) | 3.5 (2.2-4.5) | 2.2 (1.9-4.8) | 3.6 (2.7-4.5) | | Cmin (mg/L) | 0.69 (0.43-1.4) | 0.43 (0.36-0.73) | 0.69 (0.50-1.44) | | Cl/kg (L/h*kg) | 2.1 (1.5-3.2) | 2.8 (1.4-3.4) | 1.9 (1.5-3.1) | | M8/NFV AUC ratio | 0.29 (0.20-0.42) (n=14) | 0.34 (0.10-0.55) (n=6) | 0.29 (0.22-0.40) (n=8) |
Overall, 10/24 children had a NFV AUC < 12.5 mg/L*h. A NFV dosage of 20 mg/kg q8h seemed to be associated with increased risk for a subtherapeutic AUC when compared to higher NFV dosages (OR 8.7, 95% CI: 0.79 - 95). In children < 2 years old, a trend was observed to lower NFV levels and higher Cl/kg than in older children.
Conclusion:
NFV PK show high interindividual variability in children. A NFV dose of 20 mg/kg qh8 seems inadequate to reach therapeutic NFV levels in children. In addition, children younger than 2 years old may be at increased risk for subtherapeutic NFV levels.
The XIV International AIDS Conference
Abstract no.
TuPeB4557
Suggested Citation
" A S Bergshoeff , , et al.
Nelfinavir (NFV) pharmacokinetics (PK) in HIV infected children: who are at risk for subtherapeutic plasma levels?
.
Poster Exhibition:
The XIV International AIDS Conference:
Abstract no.
TuPeB4557"
|
|
|