TY - JOUR T1 - Pharmacokinetic evaluation of drug interactions with anti-human immunodeficiency virus drugs. V. Effect of soluble CD4 on 2',3'-dideoxycytidine kinetics in monkeys. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 396 LP - 401 VL - 20 IS - 3 AU - M Qian AU - A R Swagler AU - K L Fong AU - C S Crysler AU - M Mehta AU - J M Gallo Y1 - 1992/05/01 UR - http://dmd.aspetjournals.org/content/20/3/396.abstract N2 - This study was conducted to determine if soluble CD4 (ST4) altered the pharmacokinetics of 2',3'-dideoxycytidine (ddC) in nonhuman primates. Each of six monkeys received 5 mg/kg of ddC iv in the absence and presence of two different iv regimens of ST4. The ST4 regimens produced steady-state plasma concentrations of 10.3 micrograms/ml (N = 3) and 22.2 micrograms/ml (N = 3) for 30 min following ddC administration. Pharmacokinetic parameters for ddC and ST4 were calculated based on plasma and urine concentrations of ddC and plasma concentrations of ST4. Following combined ddC and ST4 administration, in both the low- and high-dose ST4 groups, plasma concentration-time profile of ddC were similar for each monkey, and no statistical differences were observed in the pharmacokinetic parameters compared with those obtained when ddC was given alone. Complete urinary excretion data for ddC was obtained in 3 of the 6 animals studied. At the low ST4 dose, one animal had a reduced renal clearance of ddC, whereas at the high ST4 dose two animals recorded an increased renal clearance of ddC. ST4 plasma concentrations were comparable to in vitro concentrations of antiviral activity, with pharmacokinetic parameters similar to those reported previously. The kinetic information provides a basis for rational dosage design for combination chemotherapeutic regimens of ddC and ST4 in human immunodeficiency virus infection. ER -