Population differences in ganciclovir clearance as determined by nonlinear mixed-effects modelling.
We examined the pharmacokinetics of ganciclovir in different populations of cytomegalovirus (CMV)-infected patients through the use of nonlinear mixed-effects modelling. As expected, patient weight and estimated creatinine clearance were shown to be important covariates in the serum ganciclovir clearance. Unexpectedly, major differences in ganciclovir clearance between different populations of patients were found. Human immunodeficiency virus (HIV)-infected patients with CMV retinitis cleared ganciclovir 41% faster than HIV-infected patients only shedding CMV into the urine. Solid-organ transplant patients had a serum clearance one-fourth that of HIV-infected patients, even with correction for creatinine clearance. These findings require prospective validation and may have important implications for ganciclovir dosing in different populations of CMV-infected patients.
Yuen
G J
GJ
Glaxo Pharmaceuticals, Research Triangle Park, North Carolina, USA.
Drusano
G L
GL
Fletcher
C
C
Capparelli
E
E
Connor
J D
JD
Lalezari
J P
JP
Drew
L
L
Follansbee
S
S
Busch
D
D
Jacobson
M
M
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D003586:Cytomegalovirus Infections / Q000188:drug therapy; D015774:Ganciclovir / Q000493:pharmacokinetics*; D006801:Humans; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D012173:Retinitis / Q000188:drug therapy
D000998:Antiviral Agents; D015774:Ganciclovir