Dm. Burger et al., Pharmacokinetics of the protease inhibitor indinavir in human immunodeficiency virus type 1-infected children, ANTIM AG CH, 45(3), 2001, pp. 701-705
The objective of this study was to evaluate the pharmacokinetics of indinav
ir in human immunodeficiency virus-infected children as part of a prospecti
ve, open, uncontrolled, multicenter study in The Netherlands. Human immunod
eficiency virus type 1-infected children were monitored over 6 months of tr
eatment with zidovudine (120 mg/m(2) every 8 h [q8h]), lamivudine (4 mg/kg
of body weight q12h), and indinavir (33 mg/kg of metabolic weight [MW] q8h)
, Four weeks after the start of treatment, the steady-state pharmacokinetic
s of indinavir were determined by high-pressure liquid chromatography. If p
atients had an indinavir area under the concentration-time curve (AUC) of b
elow 10 or above 30 mg/liter . h, a dose increase or a dose reduction was m
ade and pharmacokinetic measurements were repeated 4 weeks later. Nineteen
patients started with the dose of 33 mg/kg of MW q8h, The median AUC (range
) was 10.5 (2.8 to 51.0) mg/liter . h, The median AUC (range) in 17 childre
n treated with 50 mg/kg of MW q8h was 20.6 (4.1 to 38.7) mg/liter . h, Fina
lly, five patients had a dose increase to 67 mg/kg of MW q8h, resulting in
a median AUC (range) of 36.6 (27.2 to 80.0) mg/liter . h, After 6 months of
treatment, there were 11 children with an AUC of below 20 mg/liter . h, of
whom 5 (45%) had a detectable viral load, while this was the case in none
of the 11 children with an AUC of higher than 20 mg/liter . h, We conclude
that the optimal dose of indinavir in children to obtain drug exposure simi
lar to that observed in adult patients is 50 mg/kg of MW q8h, which approxi
mates 600 mg/m(2) q8h, It would even be better to adjust the indinavir dose
based on an AUC of greater than 20 mg/liter . h.