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Treatment in Pregnant Women and Children: Pharmacokinetics
Wednesday, 1:30 - 3:30 pm
Background: Lopinavir/ritonavir (LPV/r; Kaletra) is FDA-approved for use in children at a dose of 230 mg/M2/dose by mouth every 12 hours, and has been shown to be safe up to a dose of 300 mg/M2/dose by mouth every 12 hours in children. Safety of higher doses in children and adolescents has not been reported.
Methods: In this retrospective observational study
we examined patient records for LPV/r administered dose (mg/M2/dose),
drug exposure (LPV plasma concentration 12 hours post-dose), and possible drug-related
toxicity in pediatric and adolescent patients cared for in a single HIV clinic,
and treated with more than 300 mg/M2/dose of LPV/r between
Results: Of 16 children and adolescents with perinatally acquired HIV infection treated with LPV/r, 12 (median age 10.3 years; range 1.7 to 17.6 years) were treated with doses higher than 300 mg/M2/dose by mouth every 12 hours (median dose 376 mg/M2/dose by mouth every 12 hours; range 319 to 467). Median LPV plasma concentration in these 12 patients was 8.7 mg/mL (range 3.9 to 16.9) measured at a median of 12.0 hours after an administered dose (range 11.5 to 13h). LPV plasma concentration was only weakly correlated with administered dose (r = 0.53, p = 0.08; figure) For 4 subjects treated concurrently without an NNRTI the median LPV/r dose was 401 mg/M2/dose by mouth every 12 hours (range 346 to 467), and the median LPV/r plasma concentration was 9.9 mg/mL (range 5.3 to 16.9). For 8 subjects treated concurrently with an NNRTI, the median LPV/r dose was 372 mg/M2/dose every 12 hours (range 319 to 454), and the median LPV/r plasma concentration was 8.5 mg/mL (3.9 to 16.0). During a median duration of therapy of 1.3 years (range 0.2 to 2.9) there were no patients with drug-related toxicity that required dose reduction or change in LPV therapy.
Conclusions: These high doses of LPV/r are well tolerated in children and adolescents. The relationship between administered dose and plasma concentration demonstrates that within an individual subject, drug exposure cannot be predicted from administered dose.
Keywords: Children; lopinavir; pharmacokinetics