The pharmacokinetics and safety profile of oral ganciclovir combined with zalcitabine or stavudine in asymptomatic HIV- and CMV-seropositive patients

Two open-label, randomized multiple-dose, three-way crossover studies were performed to assess the pharmacokinetics and safety of oral ganciclovir 100 0 mg q8h in asymptomatic patients seropositive for human immunodeficiency v irus and cytomegalovirus. Ganciclovir was administered alone and in combina tion with zalcitabine 0.75 mg q8h (study 1) or stavudine 40 mg q12h (study 2). In the presence of zalcitabine, the only statistically significant chan ge in the pharmacokinetic parameters of ganciclovir was a 22.2% mean increa se in AUC(0-8). However, there was no significant change in the renal clear ance of ganciclovir when coadministered with zalcitabine, suggesting that t he increase in serum ganciclovir concentration cannot be attributed to comp etition for active renal tubular secretion. No change in zalcitabine pharma cokinetics was observed in combination with ganciclovir. There were no sign ificant changes in the pharmacokinetics of ganciclovir or stavudine when co administered. Ganciclovir was well tolerated when given alone and in combin ation with either zalcitabine or stavudine. (C) 1999 the American College o f Clinical Pharmacology.