Effects of bile salts on the lovastatin pharmacokinetics following oral administration to rats.

This study aimed to examine the effects of bile salts on pharmacokinetics of lovastatin, which has low bioavailability. Lovastatin solid dispersions were prepared using sodium deoxycholate (NaDC) and sodium glycholate (NaGC) at ratios of 1:19, 1:49, and 1:69. The formulated solid dispersions and control (commercial tablet) were administered to rats and plasma concentrations were determined by a validated LC-MS/MS method.

Pharmacokinetics and therapeutic effects of oltipraz after consecutive or intermittent oral administration in rats with liver cirrhosis induced by dimethylnitrosamine.

Pharmacokinetics and therapeutic effects of oltipraz were evaluated after consecutive (once per day at 30 mg/kg/day for 7 and 14 days) or intermittent (once per week at 100 mg/kg/week for 1-3 weeks) oral administration to rats with liver cirrhosis induced by dimethylnitrosamine. The AUC of oltipraz was significantly greater in cirrhotic rats than controls (890 compared with 270 microg . min/mL) due to impaired liver function in cirrhotic rats.

Pharmacokinetics of oltipraz in mutant Nagase analbuminemic rats.

Pharmacokinetic parameters of oltipraz were compared after intravenous (10 mg/kg) and oral (50 mg/kg) administration to control male Sprague-Dawely rats and mutant Nagase analbuminemic rats (NARs). In NARs, the expression and mRNA level of CYP1A2 increased, and oltipraz was mainly metabolized via CYP1A1/2, 2B1/2, 2C11, 201, and 3A1/2 in male rats. Hence, it may be expected that the CL of oltipraz would be significantly faster in NARs.

Pharmacokinetics of oltipraz in rat models of diabetes mellitus induced by alloxan or streptozotocin.

Pharmacokinetic parameters of oltipraz were compared after intravenous (10 mg/kg) and oral (30 mg/kg) administration in rat model of diabetes mellitus induced by alloxan (rat model of DMIA) or streptozotocin (rat model of DMIS) and their respective control male Sprague-Dawley rats. In rat models of DMIA and DMIS, the expressions and mRNA levels of CYP1A2, 2B1/2, and 3A1(23) increased, and oltipraz was metabolized mainly via CYP1A1/2, 2B1/2, 2C11, 2D1, and 3A1/2 in male Sprague-Dawley rats. Hence, it would be expected that the AUC and CL values of oltipraz would be significantly smaller and faster, respectively, in rat models of diabetes.

Effects of cysteine on the pharmacokinetics of oltipraz in rats with protein-calorie malnutrition.

Effects of cysteine on the pharmacokinetics of oltipraz were investigated after iv (10 mg/kg) and oral (30 mg/kg) administration to male control, protein-calorie malnutrition (PCM), and PCM with oral cysteine supplementation (PCMC) rats. It was reported that oltipraz was mainly metabolized via hepatic CYP1A1/2, 2B1/2, 2C11, 3A1/2, and 2D1 in male rats. The expression and mRNA levels of CYP1A2, 2C11, and 3A1/2 were also reported to decrease in male PCM rats compared with controls.

Effect of enzyme inducers and inhibitors on the pharmacokinetics of oltipraz in rats.

A series of in-vitro and in-vivo experiments, using various inducers and inhibitors of hepatic microsomal cytochrome P450 (CYP) isozymes, was conducted to study oltipraz pharmacokinetics in rats. In in-vivo studies, oltipraz at a dose of 10 mg kg(-) was administered intravenously to rats. In rats pretreated with SKF 525-A (a nonspecific CYP isozyme inhibitor in rats; n-9), the time-averaged total body clearance (CL) of oltipraz was significantly slower (56.

Interspecies pharmacokinetic scaling of oltipraz in mice, rats, rabbits and dogs, and prediction of human pharmacokinetics.

Dose-independent pharmacokinetics of oltipraz after intravenous and/or oral administration at various doses to mice, rats, rabbits and dogs were evaluated. After both intravenous and/or oral administration of oltipraz to mice (5, 10 and 20 mg/kg for intravenous and 15, 30 and 50 mg/kg for oral administration), rats (5, 10 and 20 mg/kg for intravenous and 25, 50 and 100 mg/kg for oral administration), rabbits (5, 10 and 30 mg/kg for intravenous administration) and dogs (5 and 10 mg/kg for intravenous and 50 and 100 mg/kg for oral administration), the total area under the plasma concentration-time curve from time zero to time infinity (AUC) values of oltipraz were dose-proportional in all animals studied. Animal scale-up of some pharmacokinetics parameters of oltipraz was also performed based on the parameters after intravenous administration at a dose of 10 mg/kg to mice, rats, rabbits and dogs.

The effect of lipoprotein-associated cyclosporine on drug metabolism and toxicity in rats.

Purpose: The objective of the study was to examine the effect of lipoprotein-associated cyclosporine on hepatic metabolism, hepatic lipoprotein receptors, and renal toxicity in comparison to the current commercially available cyclosporine (CSA) product.

Methods: Rats within the same group were given one of the following treatments: 10 mg/kg of CSA, plasma-CSA, very low-density lipoprotein (VLDL)-CSA, low-density lipoprotein (LDL)-CSA, LDL, high-density lipoprotein (HDL)-CSA, 1 mL/kg of vehicle, or saline intravenously for 14 days. Urine and blood samples were evaluated for renal function.

Effect of high-density lipoprotein associated cyclosporine on hepatic metabolism and renal function.

Cyclosporine (CSA), in both humans and animals, is associated with plasma lipoproteins. It has been demonstrated that CSA-lipoprotein association is partly responsible for the distribution and toxicity related to CSA use. Altered plasma lipoprotein profiles are often seen in transplantation recipients undergoing CSA treatment.