The pharmacokinetics and safety profile of oral ganciclovir in combination with trimethoprim in HIV- and CMV-seropositive patients.
OBJECTIVE
We investigated the pharmacokinetics and safety profile of oral ganciclovir coadministered with trimethoprim in HIV-and CMV-seropositive patients.


METHODS
In an open-label, randomized, 3-way crossover study, 12 adult males received oral ganciclovir 1000 mg every 8h, oral trimethoprim 200 mg once daily, or both drugs concomitantly in a sequence of three 7-day treatment periods. Pharmacokinetic parameters were determined and adverse events recorded for each treatment.


RESULTS
The presence of trimethoprim significantly decreased CLr (12.9%, P=0.0068) and increased t1/2 (18.1%, P=0.0378) of ganciclovir. However, these changes are unlikely to be clinically meaningful. There were no statistically significant changes in trimethoprim pharmacokinetic parameters in the presence of ganciclovir, with the exception of a 12.7% increase in Cmin. Ganciclovir was well tolerated when administered alone or in combination with trimethoprin.


CONCLUSIONS
There was no clinically significant pharmacokinetic interaction between oral ganciclovir and trimethoprim when coadministered.
Jung
D
D
Roche Global Development, Palo Alto, CA 94304, USA.
AbdelHameed
M H
MH
Hunter
J
J
Teitelbaum
P
P
Dorr
A
A
Griffy
K
K
D000284:Administration, Oral; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D018592:Cross-Over Studies; D003587:Cytomegalovirus / Q000187:drug effects / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D004359:Drug Therapy, Combination; D005076:Exanthema / Q000139:chemically induced; D015774:Ganciclovir / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006678:HIV / Q000187:drug effects / Q000276:immunology; D006679:HIV Seropositivity / Q000188:drug therapy*; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D014295:Trimethoprim / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000890:Anti-Infective Agents; D014295:Trimethoprim; D015774:Ganciclovir