Pharmacokinetics, skin absorption, stability, blood partition, and protein binding of AS 2-006A, a new wound healing agent.
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 microg/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 microg/mL.
Kim
G B
GB
College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, Republic of Korea.
Kim
Y G
YG
Kim
S H
SH
Park
H G
HG
Jew
S S
SS
Lee
M G
MG
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D004355:Drug Stability; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption; D014018:Tissue Distribution; D014315:Triterpenes / Q000493:pharmacokinetics*; D014945:Wound Healing / Q000187:drug effects*
C406665:AS 2-006A; D001798:Blood Proteins; D014315:Triterpenes