Acyclovir therapy in neonates.
OBJECTIVE
To determine the pharmacokinetic parameters of acyclovir disposition in neonates with renal dysfunction.


METHODS
Prospective sequential open enrollment of neonates with presumed herpes group virus infections.


METHODS
Neonatal intensive care units in the greater Minneapolis-St. Paul metropolitan area.


METHODS
Sixteen neonates with gestational ages between 27 and 40 weeks (median 38 weeks) were given acyclovir between days 1 and 56 of life to treat presumed herpes virus infections. Six infants were critically ill with multisystem disease, five infants had hepatic failure and underwent blood exchange transfusion, and five infants had renal failure. A mean of four (range 1 to 19) serum acyclovir concentrations per patient were measured by radioimmunoassay. Pharmacokinetic parameters were calculated from acyclovir concentrations in 46 samples from 16 patients.


RESULTS
The pharmacokinetic disposition of acyclovir was described as a two-compartment model. Although the ranges for acyclovir clearance and terminal elimination (t 1/2 beta) were wide, a statistically significant relationship was demonstrated between clearance and beta versus serum creatinine concentration. The average t 1/2 beta for infants with serum creatinine level less than 1 mg/dl (88 mumol/L) was 5.0 hours, and 15.6 hours for those with serum creatinine level greater than 1 mg/dl.


CONCLUSIONS
Neonates with hepatic or renal dysfunction or young premature infants accumulate acyclovir when dosed without adjustment for organ dysfunction. Measurement of serum creatinine or creatinine clearance can be useful in the dosing of acyclovir in neonates.
Englund
J A
JA
Department of Pediatrics, University of Minnesota Hospital, Minneapolis.
Fletcher
C V
CV
Balfour
H H
HH
D000212:Acyclovir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003404:Creatinine / Q000097:blood; D006561:Herpes Simplex / Q000150:complications / Q000188:drug therapy*; D006562:Herpes Zoster / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D007674:Kidney Diseases / Q000150:complications / Q000503:physiopathology; D008107:Liver Diseases / Q000150:complications / Q000503:physiopathology; D011446:Prospective Studies
D003404:Creatinine; D000212:Acyclovir