吡喹酮对映异构体与血浆蛋白结合的立体选择性

THE STEREOSELECTIVE BINDING OF PRAZIQUANTEL ENANTIOMERS TO PLASMA PROTEINS

本实验用平衡透析法研究吡喹酮(POT)对映异构体与血浆蛋白结合的立体选择性。当透析液药物初始浓度在1～32μmol/L范围内时,(±)-POT及其对映异构体与血浆蛋白的结合属非饱和类型。无论牛血清白蛋白(BSA)然度为1.47或5.88×10^(-4)mol/L,(+)-PQT结合能力(nK)均大于(-)-POT,表现较明显的立体选择性。(-)-和(+)-PQT与兔血浆蛋白结合率分别为73.7±4.4和58.3±10.1%(n=8,p<0.05),其立体选择性与BSA结合的选择方向相反。(-)-和(+)-POT与人血浆蛋白结合率分别为81.9±4.2和83.2±6.9%(n=10,P>0.05),无明显立体选择性。POT对映异构体和血浆蛋白结合立体选择性表现种属差异。

The stereoselective binding of praziquantel (PQT) enantiomers to plasma proteins was studied by equilibrium dialysis. The binding of (±) -PQT and its enantiomers to bovine serum albumin (BSA)and rabbit plasma was unsaturable when initial drug concentrations from 1 to 32μmol/L were used. The binding capacity (nK) of (+)-PQT to BSA (1.47 or 5.88× 10^(-4) mol/L)was greater than that of(-)-PQT with a (+) -/(-) - PQT ratio of 1.25 or 1.26, respectively. However, the preferential binding of (-) - PQT to rabbit plasma was found to be 73.7±4.4% for (-) - isomer and 58.3± 10.1% for(+ )-isomer (n=8, P<0.05). Thebinding of(+ )-and (-) -PQT to human plasma was 81.9±4.2% and 83.2±6.9% (n= 10, P>0.05) respectively, which seems to be not stereoselective. These results indicate that there are species differences in the stereoselective binding of PQT enantiomers to plasma proteins.