Pharmacokinetics of subcutaneous azidothymidine in rhesus monkeys.
The pharmacokinetics of subcutaneous bolus and continuous infusion azidothymidine (AZT) was studied in rhesus monkeys. Three animals received 100 mg/m2 as a bolus injection both intravenously and subcutaneously, with the order of administration randomly determined. Two animals received a continuous subcutaneous infusion of 25 mg/m2 per h for 12 or 24 h. AZT was measured in plasma by a reverse-phase high-pressure liquid chromatographic assay. Following intravenous bolus administration, AZT elimination was rapid, with a mean half-life of 1.2 h and a mean clearance of 318 ml/min per m2 (range, 200 to 441 ml/min per m2). The bolus subcutaneous dose was rapidly (time to peak concentration, 15 to 30 min) and nearly completely (fraction absorbed, 92%) absorbed without evidence of local tissue toxicity. With continuous subcutaneous infusion of AZT, the steady state was attained within 4 h and steady-state concentrations in plasma in the two animals exceeded 3.0 mumol/liter. No local tissue toxicity was observed at the infusion site. The subcutaneous route may be a practical alternative to intravenous administration of AZT and deserves further clinical study.
Balis
F M
FM
Pediatric Branch, National Cancer Institute, Bethesda, Maryland 20892.
McCully
C
C
Gough
L
L
Pizzo
P A
PA
Poplack
D G
DG
D000818:Animals; D001682:Biological Availability; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008253:Macaca mulatta; D008297:Male; D015215:Zidovudine / Q000008:administration & dosage / Q000493:pharmacokinetics*
D015215:Zidovudine