| It's key to choose a suitable species for preclinical pharmacokinetic(PK) study, which is an inseparable part of new drug evaluation. Minipig is widely used in biomedical research due to its similarity to human beings. SFDA have nominated minipig to be a suitable species for preclinical PK study of new chemicals. However, minipig is not applied in preclinical study in China, that is probably because of lacking basic research in this field.CYP3A of minipig is comparatively similar to that of human being's. As a frequently used drug for treating hyperlipemia, lovastatin is a a specific substrate CYP3A4. lovastatin is an inactive lactone prodrug, which is activated in vivo when transformed toβ-hydroxyacid lovastatin(HA). HMG-CoA reductase is inhibited by HA so that endogenetic cholesterol synthesis is efficiently inhibited. Being biotransformed by CYP3A in the liver and intestine, the Fabs of lovastatin in human is only about 5%. So we study the Fabs and FPE of LV to provide evidences for Bama miniature pig using in preclinical PK study.A total of 20 health male Bama miniature pigs were randomly divided into, intravenous group, intraportal group, intraduodenum group, and intragastric group. A single dose of lovastatin was administered intragastrically(ig, 12mg/kg), intraduodenally (id, 12mg/kg) and intravenously(iv, 1.2mg/kg), intraportally(ip, 1.2mg/kg) and blood was collected via precaval vein. Lovastatin concentrations were immediately analyzed by RP-HPLC-UV method; ivAUC(S0), ipAUC(S0), idAUC(S0) and igAUC(S0) were calculated with 3p97 by Statistical moments methods so that Fabs, FPEs could be calculated; other PK parameters were computed with 3p97 basing on an fitting PK model; similarities and differences of lovastatin in vivo between experimental animals and human being were discussed on account of Fabs, FPEs and other PK parameters.The igAUC(S0) and ivAUC(S0 were 285.41 and 1030.31 (ng/ml)*h respectively. The Fabs of lovastatin in Bama miniature pig was 2.77%, which was similar to that of dog's and human's. Only 2.77% of dosage ultimately reach the systemic circulation; 97.23% was metabolited or excreted by gastrointestinal tract and liver. The Fabs of LV is similar to that of dog and human, which is different to that of rat's.The igAUC(S0) and id AUC(S0) were 285.41 and 289.44 (ng/ml)*h respectively, namely only 2.39% of ig dosage was extracted by stomach,suggesting a low gastric FPE. The id AUC(S0) and ip AUC(S0) are 289.44 (ng/ml)*h and 247.88 (ng/ml)*h, suggest that 88.32% of id dosage was extracted by intestines. In a word, low Fabs of LV in pigs could be due to considerable intestinal FPE.The ip AUC(S0) and ivAUC(S0) were 247.88 and 1030.31 (ng/ml)*h respectively. The hepatic FPE of LV in Bama miniature pig were 75.94%. Namely, hepatic FPE was another key factor to Fabs.Other PK parameters were calculated with 3p97, basing on an open, two compartment model with first-order elimination. k21 is remarkly larger than k12; Volume of central compartment (Vc ) was 2.5L/kg; CLs was 74.7 ml/min/kg, which was slightly higher than that of dog's. Concentred distrubuted in liver, LV is easy extracted and clearanced by liver, which leads to low Fabs. To conclude, PK model of LV in Bama miniature pig is an open, two compartment model with first order elimination. 98.61% of ig dosage reaching the intestine; 87.09% and 7.75% is extracted by intestine and liver; only 2.77% ultimately reach the systemic circulation. Fabs of LV in Bama miniature pig is similar to that of dog and human, which is different to that of rat's; intestinal and hepatic FPE are key factors to Fabs. Our study adds new documents to LV; provides evidences for Bama miniature pig using in preclinical PK study.
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