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Pharmacokinetics of Lovastatin and Its Metabolism in Bama Miniature Pig

Author: ZuoYanYan
Tutor: WeiZuo
School: Third Military Medical University
Course: Zoology
Keywords: Bama miniature pig RP-HPLC lovastatin pharmacokinetic
CLC: R96
Type: Master's thesis
Year: 2006
Downloads: 94
Quote: 1
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Abstract


It is important to perform preclinical pharmacokinetic study in evaluating a novel drug, and a good model animal is the basis of such a study. Dog and monkey are frequently used animal models for preclinical pharmacokinetic study in China, however, and miniature pig has never been used in pharmacokinetic study. Lovastatin, a basic drug widely used in curing AS, was chosed as model drug to investigate pharmacokinetic in Bama miniature pig. We strive to prove that Bama mininiature pig is a suitable laboratory animal for pharmacokinetic study.A highly sensitive and rapid method using reversed-phase liquid chromatography has been developed for the quantitative analysis of lovastatin in Bama miniature pig plasma. Plasma was processed using liquid–liquid extracion. The processed sample was chromatographed on Agilent ODS Hypersil C18. The mobile phase is mixture of acetonitril and sodiumdihydrogen phosphate（60:40;pH4.5）,at a flow rate of 1.0ml/min. The wavelength of UV detecion was 238nm. Column temperture was 50±0.5℃. The lowest detectable concentration of lovastatin was 1ng/ml. The recovery rate of these methods were more than 95%, RSD of intra-day and inter-day were less than 7%. Each sample was chromatographed within about 8.0 min.Blood was collected after single（2.4mg/kg, 6.0mg/kg）and multiple（2.4 mg/kg） oral administration. The the plasma concentrations of lovastatin were detected by the validated RP-HPLC method. Following an single oral（2.4mg/kg,6.0mg/kg） administration of lovastatin to Bama miniature pig in two dose groups, the plasma was determined by RP-HPLC and pharmacokinetic paramerters were caculuted by 3P97. The Tmax was（2.79±0.23）, （ 2.50±0.32）h respectively; the Cmax was（10.32±0.5）,（ 24.14±8.01）ng/ml respectively; the T1/2α was（2.36±0.13）,（2.12±0.11）h respectively;the T1/2β was（6.46±0.15）,（5.39±0.84）h and the AUC was（108.7±11.42）,（206.7±227.3）（ng/ml）*h respectively. The pharmacokinetic paramerters, Tmax ,Cmax ,T1/2α ,T1/2β was had no marked difference between two groups. Following the multiple oral administration of lovastatin to

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