Valacyclovir Pharmacokinetics in Infants With Neonatal Herpes Simplex Virus Disease

Decreasing the length of hospitalization for an infant with neonatal Herpes simplex virus (HSV) disease could potentially reduce the emotional stress and demands on families and the financial burden on healthcare systems. However, home parenteral acyclovir administration is difficult, and oral acyclovir has reduced bioavailability. Valacyclovir has favorable bioavailability in older children and adults and could be considered for use in a portion of the treatment course.

Seven infants with neonatal HSV disease were treated with parenteral acyclovir. At the completion of their 14- or 21-day course of parenteral acyclovir, they were switched to valacyclovir suspension 20 mg/kg/dose every 8 hours for at least 2 days before starting oral acyclovir suppressive therapy. While receiving parenteral acyclovir and oral valacyclovir, pharmacokinetic sampling profiles were obtained.

Following parenteral acyclovir administration, clearance, volume, half-life and area under the curve from zero to infinity were (mean ± SD): 1.1±0.4 L/h, 3.6 ± 2.0 L, 2.5 ± 1.3 hours and 70.1 ± 41.0 mg h/L. Following valacyclovir administration, oral clearance, apparent distribution volume, absorption rate constant, half-life and area under the curve from zero to infinity were: 3.1 ± 1.8 L/h, 12.3 ± 9.9 L, 3.4 ± 3.1/h, 2.7 ± 1.2 hours and 28.8 ± 16.8 mg h/L. Valacyclovir's estimated mean bioavailability was 38.7%.

The bioavailability of valacyclovir was lower than that seen in older infants and adults, and the systemic acyclovir exposure following valacyclovir (28.8 mg h/L) was 2.4 times lower than that of parental acyclovir (70.1 mg h/L). Therefore, valacyclovir suspension at the studied dose of 20 mg/kg/dose every 8 hours cannot be recommended for use in a portion of the treatment course for neonatal HSV disease.