A pilot study of the bioavailability and pharmacokinetics of 2',3'-dideoxycytidine in patients with AIDS or AIDS-related complex.
Eight patients with AIDS or ARC received four single doses of 2',3'-dideoxycytidine (ddC). The treatments included 0.5 and 5 mg oral tablets, a 0.5 mg oral solution, and a 0.5 mg intravenous infusion. Blood samples were collected for 4 to 6 h after each dose. Plasma concentrations of ddC were determined by a specific gas chromatographic-mass spectrometric (GC-MS) assay. A combination of the low dose and the assay sensitivity of 2 ng/ml limited data treatment and comparison. Mean Cmax of 8.5, 7.6, and 79.0 ng/ml occurred at mean tmax of 1.1, 1.3, and 0.9 h for the 0.5 mg oral solution, the 0.5 mg tablet, and the 5 mg tablet, respectively. A mean clearance of 5.57 ml/min/kg and volume of distribution of 0.64 L/kg were determined from the 0.5 mg intravenous infusion. Half-life values ranged between 0.95 and 2.0 h and appeared to be independent of the dose and route of administration. The bioavailability values calculated for the oral tablets were variable, ranging from 54 to 127%. Single doses of ddC were well tolerated in this population. The results of this pilot study indicate that ddC is rapidly and extensively absorbed when administered as an oral tablet or solution to fasting AIDS or ARC patients. It is also rapidly eliminated with a half-life of 1-2 h. There are no apparent differences in the absorption or elimination of ddC between 0.5 and 5 mg oral doses.
Gustavson
L E
LE
Department of Drug Metabolism, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Fukuda
E K
EK
Rubio
F A
FA
Dunton
A W
AW
D000386:AIDS-Related Complex / Q000188:drug therapy*; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016047:Zalcitabine / Q000493:pharmacokinetics* / Q000627:therapeutic use
D016047:Zalcitabine