Pharmacokinetics of acyclovir suspension in infants and children

Abstract

Eighteen children from 3 weeks to 6.9 years of age were given an oral acyclovir suspension for herpes simplex or varicella-zoster virus infections. Thirteen patients who were 6 months to 6.9 years old received 600 mg/M2 per dose, and three infants and two children less than 2 years old were given 300 mg/M2 per dose. The drug was given four times a day, except to one infant who was treated with three doses a day. Among the 13 children who received the 600-mg/M2 dose, the maximum concentration in plasma (Cmax) was 0.99 0.38 p,g/ml (mean + standard deviation), the time to maximum concentration (Tmax) was 3.0 0.86 h, the area under the curve (AUC) was 5.56 2.17 p,g h/ml, and the elimination half-life (tl/2) was 2.59 0.78 h. The three infants less than 2 months of age who received the 300-mg/M2 dose had a Cmax of 1.88 ± 1.11 ,g/ml, a Tmax of 4.10 ± 0.48 h, an AUC of 6.54 ± 4.32 ,ugg h/ml, and a tl/2 of 3.26 ± 0.33 h. The acyclovir suspension was well tolerated by young children. No adverse effects requiring discontinuation of the drug occurred.Acyclovir [9-(2-hydroxyethoxymethyl)guanine] is a nucleoside analog which inhibits the replication of herpes simplex virus (HSV) and varicella-zoster virus (VZV). Acyclovir administered parenterally is effective for the treatment of neonatal HSV infections, HSV encephalitis, and genital HSV infections (3,25,26). In immunosuppressed patients, intravenous acyclovir is useful for the therapy and suppression of HSV infections and for the therapy of VZV infections (6,9,10,14,(18)(19)(20). The oral administration of acyclovir is of benefit for the therapy and suppression of genital HSV infections in the normal adult host (2,5,9,11,17,23) and for the treatment and suppression of recurrent mucocutaneous HSV infections in immunocompromised patients (14,22).Pharmacokinetic information is available for acyclovir administered intravenously to adults and children and for the capsule formulation given to adults (4,18). The pharmacology of oral acyclovir tablets has been investigated in children (12,13). A liquid suspension formulation of the drug was developed for children and other patients who cannot ingest medications in solid form. The purpose of our study was to determine the pharmacokinetics and tolerance of acyclovir suspension in children.(This work was presented in part at the 26th Interscience

Late recurrence of herpes simplex virus meningoencephalitis in two infants

“…Furthermore, we cannot comment on compliance with therapy at home as no monitoring of serum acyclovir levels was performed, even though parents insisted that both infants were treated regularly. It is possible that the oral dose of acyclovir was too low for achieving an adequate concentration in CSF to suppress viral reactivation [19]. Oral acyclovir suppressive therapy has been determined to be most ecacious at a dose of 300 mg/m 2 (50±60 mg/kg per day) administered three times a day, whereas the same dose administered twice a day appeared to be less eective, suggesting that the dosing interval is also relevant [7].…”

An Investigation of the Steady‐State Pharmacokinetics of Oral Valacyclovir in Immunocompromised Children

“…HSV or VZV infections [12,13]. After intravenous administration, pharmacokinetic characteristics in those aged у1 year appeared similar to those of adults.…”

Pharmacokinetics of Oral Acyclovir in Neonates and in Infants: a Population Analysis

“…Patients aged between 1 month and 2 years received acyclovir at 24 mg/kg of body weight q.i.d. according to a schedule of treatment at 0, 4,8,12, and 24 h. These dosages were based on the limited pharmacokinetic data available (16,21): about 25 mg/kg per dose was expected to be adequate. The value of 24 mg/kg was retained because it corresponded to three graduations of the dosing syringe.…”

“…Oral acyclovir is also effective for the prevention of cutaneous recurrences after HSV type 2 (HSV-2) disease of the skin, eyes, and mouth in neonates at a dose of 300 mg/m 2 q8h (10). Despite the large amount of clinical experience, these dosage recommendations were substantiated with limited pharmacokinetic data obtained with neonates after oral administration (10,16,21). These preliminary data showed that the kinetics of acyclovir in neonates were probably strongly modified compared to those in adults, as expected, but acyclovir bioavailability and the interindividual variability of its pharmacokinetics could not be well characterized.…”