Kim, SO Kwak, SH Lee, BH Lee, DH Lim, H Yoo, SE Chung, HJ Lee, MG 2024-01-21T07:14:44Z 2024-01-21T07:14:44Z 2021-09-01 2004-04 0142-2782 https://pubs.kist.re.kr/handle/201004/137750 Dose-dependent pharmacokinetic parameters of KR-31378, a new neuroprotective agent for ischaemia-reperfusion damage, were evaluated after intravenous and oral administration of the drug at doses of 5, 10 and 25 mg/kg to male beagle dogs. After intravenous administration, the dose-normalized (based on 5 mg/kg) areas under the plasma concentration-time curve from time zero to time infinity (AUC values, 725, 1450 and 2300 mug min/ml for 5, 10 and 25 mg/kg, respectively) were significantly different among the three dose ranges studied; the value increased more proportionally as the dose increased. This could be due to slower total body clearance (Cl) with increasing doses (6.90, 3.46 and 2.17 ml/min/kg). The slower Cl value with increasing doses may be due to saturable metabolism of KR-31378 in dogs. After oral administration, the dose-normalized (based on 5 mg/kg) AUC values (833, 1450 and 1920 mug min/ml) at 5 mg/kg were significantly smaller than those at 10 and 25 mg/kg. Note that the AUC values were comparable (not significantly different) between intravenous and oral administration at all doses studied, indicating that the absorption of KR-31378 from the gastrointestinal tract was essentially complete and the first-pass (gastric, intestinal and/or hepatic first-pass) effects were almost negligible in dogs. Copyright (C) 2004 John Wiley Sons, Ltd. English WILEY BENZOPYRAN ANALOG (2S,3S,4R)-N&apos &apos -CYANO-N-(6-AMINO-3,4-DIHYDRO-3-HYDROXY-2-METHYL-2-DIMETHO XYMETHYL DRUGS Dose-dependent pharmacokinetics of KR-31378, a new neuroprotective agent for ischaemia-reperfusion damage in dogs Article 10.1002/bdd.391 1 BIOPHARMACEUTICS & DRUG DISPOSITION, v.25, no.3, pp.143 - 148 BIOPHARMACEUTICS & DRUG DISPOSITION 25 3 143 148 scie scopus 000221127400006 Pharmacology & Pharmacy Pharmacology & Pharmacy Article BENZOPYRAN ANALOG (2S,3S,4R)-N&apos &apos -CYANO-N-(6-AMINO-3,4-DIHYDRO-3-HYDROXY-2-METHYL-2-DIMETHO XYMETHYL DRUGS KR-31378 dose-dependent pharmacokinetics intravenous and oral administration dogs