An investigation of the steady-state pharmacokinetics of oral valacyclovir in immunocompromised children.
Valacyclovir was administered to 28 immunocompromised children (ages 5-12 years) to obtain preliminary pharmacokinetic and safety information. Patients were randomized to valacyclovir regimens of 250 mg (9.4-13.3 mg/kg) or 500 mg (13.9-27.0 mg/kg) twice daily or 500 mg (13.2-21.7 mg/kg) 3 times a day. Acyclovir pharmacokinetics were evaluated at steady state. Valacyclovir was rapidly absorbed and converted to acyclovir. Mean (+/-SD) acyclovir peak concentrations from 250 mg and 500 mg valacyclovir were 4.11+/-1.41 and 5.19+/-1.96 microg/mL, respectively. Corresponding single dose area-under-curve values were 12.14+/-6.60 and 14.49+/-4.69h microg/mL. By using historical data for intravenous acyclovir as reference, the overall estimate of acyclovir bioavailability from valacyclovir was 48%, 2- to 4-fold greater than for oral acyclovir. In general, adverse events were not attributable to valacyclovir and were consistent with disease-related expectations and concomitant therapies. Dosage options for using valacyclovir in children are discussed.
D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000704:Analysis of Variance; D019540:Area Under Curve; D001530:Belgium; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D005260:Female; D005602:France; D006561:Herpes Simplex / Q000378:metabolism* / Q000517:prevention & control; D006562:Herpes Zoster / Q000378:metabolism* / Q000517:prevention & control; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D010865:Pilot Projects; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013557:Switzerland; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
D011355:Prodrugs; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir