POPULATION DIFFERENCES IN GANCICLOVIR CLEARANCE AS DETERMINED BY NONLINEAR MIXED-EFFECTS MODELING

We examined the pharmacokinetics of ganciclovir in different populatio ns of cytomegalovirus (CMV)-infected patients through the use of nonli near mixed-effects modelling. As expected, patient weight and estimate d creatinine clearance were shown to be important covariates in the se rum ganciclovir clearance. Unexpectedly, major differences in ganciclo vir clearance between different populations of patients were found. Hu man immunodeficiency virus (HIV)-infected patients with CMV retinitis cleared ganciclovir 41% faster than HIV-infected patients only sheddin g CMV into the urine. Solid-organ transplant patients had a serum clea rance one-fourth that of HIV-infected patients, even with correction f or creatinine clearance. These findings require prospective validation and may have important implications for ganciclovir dosing in differe nt populations of CMV-infected patients.