[Study on dissolution test in vitro and bioavailability of oral osmotic pump of verapamil hydrochloride].

This paper deals with the evaluation of osmotic pump of verapamil hydrochloride tablet (C) by measuring in vitro/in vivo test. The results showed that the dissolution behaviors were of zero-order kinetic and release constant in vitro (Kr) of C was 9.9450. The plasma levels of Ver.HCl in eight volunteers following single and multiple oral doses of these dosage forms were determined using HPLC method. The pharmacokinetic parameters were fitted by nonlinear least square method with a computer on the basis of two-compartment model. The pharmacokinetic parameters of Cmax, Tmax, t1/2, Ka, K10 and K21 were calculated. The bioavailability of tablet C relative to B and A was 101.7%, 96.16% respectively. A significant correlation was found between in vitro dissolution and in vivo absorption.

Pharmacokinetic and pharmacodynamic studies of the effect of ketoconazole on reproductive function in male rats.

A single oral dose (300 mg kg-1) of ketoconazole induced reversible immobilization of rat epididymal spermatozoa at 8-24 h after dosing. This occurred when the drug concentrations in cauda epididymal fluid and seminal plasma were at their peak (18.0 +/- 7.3 and 13.5 +/- 3.0 micrograms ml-1, respectively), and which was preceded by a peak plasma concentration (Cmax) of 64.82 +/- 2.47 micrograms ml-1 at 5.15 +/- 0.68 h (Tmax). In contrast, rete testis fluid collected from the same animals contained only minute amounts of ketoconazole (0.47 +/- 0.34 micrograms ml-1). Plasma testosterone concentration showed a sharp decline within 4 h of dosing, followed by a recovery from suppression, even after administration of a low dose (100 mg kg-1) which did not affect sperm motility. These findings suggest that ketoconazole gains access to the post-testicular sex organs and affects the mature spermatozoa therein much more readily than it affects testicular spermatogenesis. Synthesis and screening of compounds with a related molecular structure but which exhibit more pronounced spermicidal and less pronounced anti-androgenic effects are thus suggested in the hope that rapidly acting and reversible male contraceptives might be identified and developed.