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Pharmacokinetics, skin absorption, stability, blood partition, and protein binding of AS 2‐006A, a new wound healing agent
Author(s) -
Kim Gi B.,
Kim Yoon G.,
Kim So H.,
Park HyeungG.,
Jew SangS.,
Lee Myung G.
Publication year - 2000
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/1099-081x(200004)21:3<113::aid-bdd219>3.0.co;2-o
Subject(s) - pharmacokinetics , volume of distribution , chemistry , blood proteins , absorption (acoustics) , blood plasma , urine , chromatography , half life , pharmacology , medicine , biochemistry , physics , acoustics
After intravenous administration of AS 2‐006A, 20, 50, and 90 mg/kg, to rats, 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), were dose‐independent. After topical application of 0.5 or 1% AS 2‐006A ointment, 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 approximately 20%. The tissue‐to‐plasma ratios of AS 2‐006A were greater than unity in all rat tissues studied, except in the muscle and large intestine. 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 disappearance rate constant was 0.0218/h. AS 2‐006A reached equilibrium fast between plasma and blood cells, and the equilibrium plasma/blood cells partition ratios were independent of the initial rabbit blood concentrations of AS 2‐006A, 10, 20, and 50 µg/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 plasma was high, as the drug was under detection limit in the filtrate at the plasma concentrations of the drug, ranging from 7.21 to 228 µg/mL. Copyright © 2000 John Wiley & Sons, Ltd.