Clinical pharmacokinetics of ganciclovir in patients with normal and impaired renal function.
The pharmacokinetics of ganciclovir was evaluated in 21 patients with life- or sight-threatening cytomegalovirus infections. Thirteen patients had normal renal function and eight patients had various degrees of renal insufficiency. Most patients received 5 mg of ganciclovir/kg as a 1-hour intravenous infusion twice daily for periods of up to 2 weeks. Quantification of ganciclovir was assessed by high-performance liquid chromatography and radioimmunoassay. In patients with normal renal function, a biexponential decay of ganciclovir from plasma was observed, with an initial distribution half-life (t1/2) of 0.76 +/- 0.67 hour and a terminal elimination t1/2 of 3.60 +/- 1.40 hours. A large fraction of the administered dose was excreted in urine, and total clearance of ganciclovir correlated well with creatinine clearance. In patients with renal insufficiency who were receiving 5 mg of ganciclovir/kg, the terminal elimination t1/2 of ganciclovir was markedly increased (11.50 +/- 3.90 hours), as compared with values obtained in patients with normal renal function. Hemodialysis efficiently reduced levels of ganciclovir in plasma by approximately 53.0% +/- 11.5%, a finding that indicates this drug should be administered after dialysis.
Sommadossi
J P
JP
Department of Pharmacology, University of Alabama, Birmingham 35294.
Bevan
R
R
Ling
T
T
Lee
F
F
Mastre
B
B
Chaplin
M D
MD
Nerenberg
C
C
Koretz
S
S
Buhles
W C
WC
D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003586:Cytomegalovirus Infections / Q000378:metabolism*; D005260:Female; D015774:Ganciclovir; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
D000998:Antiviral Agents; D015774:Ganciclovir; D000212:Acyclovir