Koo Tae-Sung, Kim Dae-Hyun, Ahn Sung-Hoon, Kim Kang-Pil, Kim In-Wha, Seo Seung-Yong, Suh Young-Ger, Kim Dae-Duk, Shim Chang-Koo, Chung Suk-Jae
Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
J Pharm Sci. 2005 Oct;94(10):2187-97. doi: 10.1002/jps.20451.
The objective of this study was to characterize the extent of the formation of the active (trans-alcohol form) and inactive (cis-alcohol) metabolites of loxoprofen and to compare the kinetics after its intragastric, intravenous, and intramuscular administrations in rats. After intravenous administration of the drug at doses of 5-20 mg/kg, the clearance and the volume of distribution for loxoprofen, and the ratios of the AUC for the metabolites to the parent drug were not statistically different with the dosage; the formation clearances were 1.08 and 0.87 mL/min/kg for the active and its isomeric metabolite, respectively. After the intragastric, intravenous, or intramuscular administration, AUC for loxoprofen and the metabolites at a dose of 10 mg/kg were not statistically different for the different routes of administration. The formation of the metabolites with the concomitant loss of loxoprofen was found in incubations with liver homogenates and blood but not with a muscle homogenate or plasma, indicating that the conversion of loxoprofen to the metabolites may occur both in the liver and extraheptic tissue(s). Thus, approximately 22% of the loxoprofen may have been converted to the active metabolite in the liver and the extraheptic tissue(s) and the pharmacokinetics of the active metabolite was independent of the route of administration.
本研究的目的是表征洛索洛芬活性（反式醇形式）和非活性（顺式醇）代谢物的形成程度，并比较其在大鼠体内胃内、静脉内和肌内给药后的动力学。以5 - 20 mg/kg的剂量静脉注射该药物后，洛索洛芬的清除率和分布容积，以及代谢物与母体药物的AUC比值在不同剂量下无统计学差异；活性代谢物及其异构体代谢物的形成清除率分别为1.08和0.87 mL/min/kg。在胃内、静脉内或肌内给药后，10 mg/kg剂量的洛索洛芬及其代谢物的AUC在不同给药途径之间无统计学差异。在与肝匀浆和血液的孵育中发现了代谢物的形成以及洛索洛芬的相应损失，但在肌肉匀浆或血浆中未发现，这表明洛索洛芬向代谢物的转化可能在肝脏和肝外组织中均会发生。因此，约22%的洛索洛芬可能已在肝脏和肝外组织中转化为活性代谢物，且活性代谢物的药代动力学与给药途径无关。
