Pharmacokinetics and Tissue Distribution of Porcine CFTR Inhibitor A in Mice

OBJECTIVE To study the pharmacokinetics and tissue distribution of pCFTRinh-A in mice.METHODS 20 mg·kg-1 pCFTRinh-A was given by intraperitoneal injection.HPLC method for the determination of pCFTRinh-A in plasma and tissues was established and applied to determine pCFTRinh-A in plasma and tissue samples.RESULTS The plasma concentration of pCFTRinh-A was found after 5 min of administration.The main pharmacokinetic parameters were as follows: t1/2ka(2.089±0.481) min,t1/2a(21.576±0.761) min,t1/2β(155.424±28.723) min,AUC(489.055±12.538) μg·min·mL-1,tmax(11.32±1.006) min,ρmax(7.461±0.143) μg·mL-1,CL(s)(0.041±0.001) L·min-1.The absorption and distribution of pCFTRinh-A was quick while elimination was slow with high bioavailability.The distribution of pCFTRinh-A was high in liver,kidney and lung,while lower in heart,spleen and intestines and lowest in brain.CONCLUSION The pharmacokinetics and tissue-distribution characters of pCFTRinh-A will be helpful for building cystic fibrosis phenotype in large animals.