Pharmacokinetics of daily and weekly dapsone in hiv-infected children

Abstract

While dapsonc (D) is widely used for PCP prophylaxis in H1V infected children with intolerance to TMP-SMX, there are limited pediatrie pbarmacokinetic data. We determined the pharmacokinetics (pk) of oral D in HIV infected children who had received at least 4 weeks of treatment with duly doses of 1 mg/kg(n=10)or 2 mg/kg (n=10), or weekly doses of 4 mg/kg(n=10) Serial serum samples for D cone were collected over 48 hours for daily dose patients and 7 days for weekly dose patients. D cone was measured by HPLC. Pk analysis was performed using noncomparmcntal methods Pk parameters (mean±SD)are shown below: Dose Age Tmix Cmax AUC Cl/F Vd/F 11/2 (JTS) (hrs) (ug/ml) (ug*hf/ml) (L/hr) (IAg) (hrs) I mg/kg daily 4.4± 2.5 ±1.57± 28.6± 0.0581 U7± 17.3± (n=10) 4.2 1.4 0.98 28.4 0.033 0.52 10.0 2mg/kg daily 4.S± 2.5 ±3.17± 4S.2± 0.047± l.25± 20.9± (n=9) 3.9 2.3 0.48 16.5 0.018 0.24 6.3 4mg/kg 5.2± 3.0± 3.55± I44.0± 0.036± 1.10± 25.8± weekly (n=9) 5.1 1.3 0.63 70.0 0.022 0.18 10.3 For the enure group. 11/2 averaged 21.3 hours (range: 5.4-46.9), compared to average adult 11/2 of 30 hours (range: 13-83) suggesting that children eliminate D faster than adults. Children receiving chronic 2 mg/kg daily doses or 4 mg/kg weekly doses achieved peak D serum cone equivalent to those seen in adults with chronic daily 100 mg doser, therefore these doses seem appropriate for children receiving D for PCP prophylaxis.