The aim of this study was to investigate effects of type 2 diabetes on the pharmacokinetics of verapamil after intravenous administration. Diabetes mellitus (DM) rats were induced by combination of high-fat diet (HFD) and streptozotocin. Plasma concentrations of verapamil in DM rats, rats fed with HFD, and control (CON) rats were measured after intravenous administration of 1 mg/kg verapamil and corresponding pharmacokinetic parameters were estimated. Area under the plasma concentration in DM rats was significantly smaller than that in CON rats. In vitro microsomal study showed that intrinsic clearance of verapamil in DM rats was significantly higher than those in CON rats. Compared to CON rats, higher intrinsic clearance was also observed in HFD rats. Western blot results demonstrated higher levels of CYP3A2 in DM and HFD rats, which was in line to activity of CYP3A. All the results gave a conclusion that diabetes may enhance metabolism of verapamil in rat, and the enhancement may partly result from induction of CYP3A.

Our aim was to investigate whether renal impairment induced by cisplatin altered the pharmacokinetics of antofloxacin. Antofloxacin (7.5 mg kg(-1), i.v.) was given to normal or renally impaired rats (induced by cisplatin). Concentrations of antofloxacin in plasma and urine were measured using HPLC. Pharmacokinetic parameters were estimated. The plasma concentrations of antofloxacin in the renally impaired rats were significantly higher than those in the normal rats, accompanied by significant increase of the area under the plasma concentration-time curve (AUC) (968.78+/-259.39 microg min mL(-1) versus 509.84+/-46.19 microg min mL(-1) in normal rats P < 0.05). The system clearance (CL) and renal clearance (CL(R)) of antofloxacin decreased from 12.66+/-1.15 mL kg(-1) min(-1) and 3.21+/-1.80 mL kg(-1) min(-1) in normal rats, to 6.63+/-2.82 mL kg(-1) min(-1) and 0.31+/-0.15 mL kg(-1)min(-1), respectively. No differences between two treatments in half-life and mean residence time were found. We concluded that renal impairment induced by cisplatin significantly altered the pharma-cokinetics of antofloxacin and resulted in decrease of the renal elimination.