Pharmacokinetic-interaction study of didanosine and ranitidine in patients seropositive for human immunodeficiency virus.
The potential pharmacokinetic interactions between didanosine, an acid-labile antiretroviral agent, and ranitidine, an H2-receptor antagonist, were evaluated by a crossover study of 12 male patients seropositive for the human immunodeficiency virus. Single oral doses of 375 mg of didanosine, formulated as a citrate-phosphate-buffered sachet, or of 150 mg of ranitidine were administered alone or in combination (ranitidine was given 2 h prior to didanosine). Serial blood samples and total urinary output were collected after each treatment and analyzed for didanosine and/or ranitidine by validated high-performance liquid chromatography-UV assay methods. Pharmacokinetic parameters were calculated by noncompartmental methods. There were significant increases in mean area under the curve from time zero to infinity and mean urinary recovery for didanosine given in combination with ranitidine compared with those for didanosine alone. There were no significant differences between didanosine coadministered with ranitidine and didanosine alone in the respective mean peak concentrations in plasma, times to peak, elimination half-lives, or renal clearances. The mean area under the curve for ranitidine given with didanosine was significantly less than that for ranitidine given alone. There were no significant differences between the mean peak concentrations in plasma, times to peak, elimination half-lives, renal clearances, or urinary recovery values for ranitidine coadministered with didanosine and values for ranitidine given alone. These data demonstrate that administration of didanosine 2 h after ranitidine will result in a minor increase in the bioavailability of didanosine. A modification in the dose of didanosine or ranitidine is not necessary if the dose of ranitidine precedes that of didanosine by 2 h.
Knupp
C A
CA
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, Syracuse, New York 13221.
Graziano
F M
FM
Dixon
R M
RM
Barbhaiya
R H
RH
D000284:Administration, Oral; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D016049:Didanosine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004347:Drug Interactions; D006679:HIV Seropositivity / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D008297:Male; D011897:Random Allocation; D011899:Ranitidine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D011899:Ranitidine; D016049:Didanosine