Pharmacokinetics, skin absorption, stability, blood partition, and proteinbinding of AS 2-006A, a new wound healing agent

After intravenous administration of AS 2-006A, 20, 50, and 90 mg/kg, to rat s, the pharmacokinetic parameters, terminal half-life (69.8-86.6 min), mean residence time (56.2-75.2 min), apparent volume of distribution at steady state (809-1040 mL/kg), and total body clearance (11.4-11.9 mL/min/kg), wer e dose-independent. After topical application of 0.5 or 1% AS 2-006A ointme nt, 300 mg, to abraded rat skin, the absorbed amounts were dose (0.5 and 1% ) and time (30, 60, 120, 240, 360 and 480 min)-independent; the value was a pproximately 20%. The tissue-to-plasma ratios of AS 2-006A were greater tha n unity in all rat tissues studied, except in the muscle and large intestin e. AS 2-006A was stable for up to 24 h incubation in rat plasma, and human plasma and urine; however, it seemed not to be stable in rat urine; the dis appearance rate constant was 0.0218/h. AS 2-006A reached equilibrium fast b etween plasma and blood cells, and the equilibrium plasma/blood cells parti tion ratios were independent of the initial rabbit blood concentrations of AS 2-006A, 10, 20, and 50 mug/mL; the mean values were in the range of 2.38 -2.75 for three rabbit blood. The protein binding of AS 2-006A to rat plasm a was high, as the drug was under detection limit in the filtrate at the pl asma concentrations of the drug, ranging from 7.21 to 228 mug/mL. Copyright (C) 2000 John Wiley & Sons, Ltd.