[Pharmacokinetics and relative bioavailability of probucol inclusion complex capsule in healthy dogs].
OBJECTIVE
To study the pharmacokinetics and relative bioavailability of probucol inclusion complex capsule.


METHODS
Following 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.


RESULTS
The 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.


CONCLUSIONS
The 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.
Zhang
Zheng
Z
Department of Pharmacy, Cardiovascular Institute and Fu Wai Hospital, Beijing 100037, China.
Chen
Bao-ling
BL
Wang
Ke
K
Huang
Yi-ling
YL
Fang
Shu-qing
SQ
Gu
De-liang
DL
Fang
Li
L
Han
Shao-jun
SJ
D000284:Administration, Oral; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002214:Capsules; D004285:Dogs; D005260:Female; D011341:Probucol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011897:Random Allocation; D013607:Tablets
D000924:Anticholesteremic Agents; D002214:Capsules; D013607:Tablets; D011341:Probucol