This study pharmacokinetically examined the lovastatin sustained-release tablet and sustained-release capsule in Beagle dogs. An reversed-phase HPLC method was established for the determination of lovastatin in Beagle dog plasma. Pharmacokinetic findings were compared among three preparation(lovastatin sustained-release tablet, Tp; sustained-release capsule, TJ and conventional capsule). Our results showed that the pharmacokinetic parameters in 6 dogs after single-dose oral administration of three perparations were calculated. Tmax, Cmax and MRT revealed significant difference (P<0.05). Relative bioavailability was 111.5 +/- 16.9% (Tp) and 110.4% +/- 9.6% (Tj). The pharmacokinetic parameters in the 6 dogs after multiple-dose oral administration of three perparations, Tmax, Cmax MRT and DF had significant difference (P < 0.05); Cav, Cmin and AUC0-24 h displayed no significant difference (P>0.05). It is concluded that the lovastatin sustained-release tablet and sustained-release capsule are able to maintain a sustained-release for 24 h.
Anticholesteremic Agents/*pharmacokinetics ; Capsules ; Delayed-Action Preparations ; Lovastatin/*pharmacokinetics ; Tablets

This study pharmacokinetically examined the lovastatin sustained-release tablet and sustained-release capsule in Beagle dogs. An reversed-phase HPLC method was established for the determination of lovastatin in Beagle dog plasma. Pharmacokinetic findings were compared among three preparation(lovastatin sustained-release tablet, Tp; sustained-release capsule, TJ and conventional capsule). Our results showed that the pharmacokinetic parameters in 6 dogs after single-dose oral administration of three perparations were calculated. Tmax, Cmax and MRT revealed significant difference (P<0.05). Relative bioavailability was 111.5 +/- 16.9% (Tp) and 110.4% +/- 9.6% (Tj). The pharmacokinetic parameters in the 6 dogs after multiple-dose oral administration of three perparations, Tmax, Cmax MRT and DF had significant difference (P < 0.05); Cav, Cmin and AUC0-24 h displayed no significant difference (P>0.05). It is concluded that the lovastatin sustained-release tablet and sustained-release capsule are able to maintain a sustained-release for 24 h.
Animals ; Anticholesteremic Agents ; pharmacokinetics ; Capsules ; Delayed-Action Preparations ; Dogs ; Female ; Lovastatin ; pharmacokinetics ; Male ; Tablets

AIMTo study the pharmacokinetics and relative bioavailability of probucol inclusion complex capsule.

METHODSFollowing oral administration of a single dose of 250 mg of conventional tablet (formulation A, purchased from the market) and probucol inclusion complex capsule (formulation B, a new formulation for preclinical trial) to each of 6 healthy dogs in a randomized crossover design, the plasma levels of the active drug at different time points were determined by HPLC and the plasma concentration-time profiles of formulation A and B were obtained. The pharmacokinetic parameters as well as relative bioavailability were analyzed.

RESULTSThe concentration-time curves of formulation A and formulation B were found to fit a two-compartment open model. The Tmax values of formulation A and formulation B were (9.3 +/- 2.1) h and (9.3 +/- 2.1) h, the Cmax values were (1.5 +/- 1.0) microgram.mL-1 and (2.3 +/- 0.9) microgram.mL-1 and the AUC0-240 values were (85 +/- 56) microgram.h.mL-1 and (134 +/- 55) microgram.h.mL-1, respectively. The relative bioavailability of formulation B was found to be (198 +/- 90)% compared with formulation A. The results of variance analysis and two one-side t-test showed that there was significant difference between the two formulations in the AUC0-240.

CONCLUSIONThe high bioavailability by the inclusion of formulation B is attributed to the improvement of its water-solubility by the inclusion process and this is supposed to be a key factor for improving drug bioavailability.

Administration, Oral ; Animals ; Anticholesteremic Agents ; administration & dosage ; pharmacokinetics ; Biological Availability ; Capsules ; Dogs ; Female ; Probucol ; administration & dosage ; pharmacokinetics ; Random Allocation ; Tablets

The object of this study is to investigate the pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in healthy adult Beagle dogs following single and multiple oral dose administration. A randomized, cross-over study was conducted with nine healthy adult Beagle dogs assigned to three groups. Each group was arranged to take atorvastatin calcium (A), pioglitazone hydrochloride (B), atorvastatin calcium and pioglitazone hydrochloride (C) orally in the first period, to take B, C, A in the second period, and to take C, A, B in the third period for 6 days respectively. The blood samples were collected at the first and the sixth day after the administration, plasma drug concentrations were determined by LC-MS/MS, a one-week wash-out period was needed between each period. The pharmacokinetic parameters of drug combination group and the drug alone group were calculated by statistical moment method, calculation of C(max) and AUC(0-t) was done by using 90% confidence interval method of the bioequivalence and bioavailability degree module DAS 3.2.1 software statistics. Compared with the separate administration, the main pharmacokinetic parameters (C(max) and AUC(0-t)) of joint use of pioglitazone hydrochloride and atorvastatin calcium within 90% confidence intervals for bioequivalence statistics were unqualified, the mean t(max) with standard deviation used paired Wilcoxon test resulted P > 0.05. There was no significant difference within t1/2, CL(int), MRT, V/F. Pioglitazone hydrochloride and atorvastatin calcium had pharmacokinetic interaction in healthy adult Beagle dogs.
Administration, Oral ; Animals ; Anticholesteremic Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Atorvastatin Calcium ; administration & dosage ; blood ; pharmacokinetics ; Biological Availability ; Cross-Over Studies ; Dogs ; Drug Interactions ; Female ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; administration & dosage ; blood ; pharmacokinetics ; Hypoglycemic Agents ; administration & dosage ; blood ; pharmacokinetics ; Male ; Random Allocation ; Thiazolidinediones ; administration & dosage ; blood ; pharmacokinetics