Background:  Emtricitabine (FTC) is a potent once-daily nucleoside reverse transcriptase inhibitor (NRTI) approved for the treatment of HIV infection in adults and children ³3 months in age in combination with other antiviral agents. Since FTC is primarily eliminated by renal excretion, and because renal function matures during the first few months of life, FTC pharmacokinetics was examined at steady-state following short-term administration in HIV-exposed infants <3 months to determine an appropriate dose for this age group that would provide drug exposure similar to that achieved by regimens shown to be safe and efficacious in pediatric patients (6 mg/kg oral solution £240 mg once daily) and adult patients (200 mg capsules once daily).

Methods:  Neonates born to women with confirmed HIV-1 infection, and who received 6 weeks of postnatal zidovudine prophylaxis for perinatal HIV exposure, received 2 short courses of FTC (each 3 mg/kg once daily for 4 days) as oral solution during the first 12 weeks of life. Confirmed HIV-infected neonates were excluded from the study. The first FTC course was administered during the first 28 days of life and the second administered as long as 8 weeks later and staggered among neonates. Plasma pharmacokinetics was assessed over 48 hours following the administration of the last dose of each course.

Results:  We enrolled 22 infants, and 20 completed both pharmacokinetic assessments. One infant received 1 dose of FTC and was lost to follow-up, and 1 discontinued due to anemia unrelated to FTC. (Pharmacokinetic parameters are summarized in the table.) FTC area under the curve (AUC) decreased with increasing age over the first 3 months of life which correlated with an increase in apparent total body clearance (CL/F). However, the AUC in neonates receiving 3 mg/kg FTC QD during the first 3 months of life was in the range of pediatric patients ³3 months to 17 years receiving 6 mg/kg oral solution to as much as 240 mg once daily as or 200-mg capsules once daily.

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Conclusions:  Results indicate that 3 mg/kg FTC once daily in neonates <3 months old produces plasma levels similar to those shown to be safe and efficacious in HIV-infected adults and pediatric patients ³3 months.