Use of Raltegravir in Pediatric HIV-1 Infection

Marcia L. Buck, Pharm.D., FCCP, FPPAG; Kristi N. Hofer, Pharm.D; Michelle W. McCarthy, Pharm.D.; FASHP Susan B. Cogut, Pharm.D

Disclosures

Pediatr Pharm. 2012;18(1) 

In This Article

Pharmacokinetics

In adults, an oral dose of raltegravir reaches peak plasma concentrations within 0.5–1.5 hours. Bioavailability is approximately 30%. Administration with food does not appear to have a clinically significant effect on overall patient response. A mean area under the concentration curve (AUC0–12 hrs) of 14.3 microM·hr and a mean concentration at 12 hours (C12hr) of 142 nM have been reported in adults receiving 400 mg raltegravir twice daily. Raltegravir is 83% bound to plasma proteins. It is highly metabolized, primarily to raltegravir-glucuronide via uridine diphosphate glucuronosyltranserase 1A1 (UGT1A1). In adults, the terminal half-life is approximately 9 hours (range 7–12 hours). UGT1A1 polymorphisms do not appear to affect raltegravir clearance. A study comparing mean AUC values in poor metabolizers (the *28/*28 genotype) and the wild-type genotype revealed no significant differences.[2–5]

A pharmacokinetic study conducted in 44 children taking part of the IMPAACT P1066 study produced similar results to studies in adults.[3] In the first stage of the study, children 6–18 years of age were given doses of 6 or 8 mg/kg twice daily; this was subsequently changed to dose stratification by age and weight based on the availability of new 25 and 100 mg chewable tablets. Adolescents 12 years of age and older and children between 6 and 12 years of age who weighed at least 25 kg were given the standard adult dose of 400 mg twice daily. Children from 6 to 12 years who weighed less than 25 kg and children 2 to 6 years of age who weighed at least 10 kg received raltegravir doses according to weight: 75 mg twice daily for patients 10–13.9 kg, 100 mg twice daily for patients 14–19.9 kg, 150 mg twice daily for patients 20–27.9 kg, 200 mg twice daily for patients 28–39.9 kg, and 300 mg twice daily for patients ≥ 40 kg. Children between 6 and 12 years of age who weighed < 25 kg received the chewable tablet, and those weighing ≥ 25 kg were given the film-coated tablet. Mean AUC0–12 hrs values (Table 1) were similar among the groups, while C12hr increased with increasing age or weight.[3]

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