ABSTRACT
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.
Subject(s)
Verapamil/pharmacokinetics , Adult , Biological Availability , Chromatography, High Pressure Liquid , Delayed-Action Preparations , Humans , Male , Solubility , Verapamil/administration & dosageABSTRACT
Rats were treated with highly purified gossypol acetic acid at doses of 15 or 30 mg/kg day-1 for 6 weeks to produce an effect on spermatogenesis as shown by reduced sperm motility and increased sperm malformation rates. The treated rats did not differ from the controls in the body weight growth curves and reproductive organ weights. When stimulated with hCG, testicular blood flow was increased in the low dose group; the testosterone concentrations in peripheral and testicular venous blood were also increased to a greater extent than those of the control group. No difference was found between the high dose and control groups in testicular blood flow or testosterone concentrations. The morphology of the Leydig cells was apparently normal, although some degenerative changes in the germinal epithelium were observed in the high dose group. Therefore, there is no evidence in our experiment to show any anti-androgenic effect following 6-week treatment of gossypol in rats, even at the dose of 30 mg/kg day-1.
Subject(s)
Gossypol/pharmacology , Testis/drug effects , Testosterone/blood , Animals , Body Weight/drug effects , Chorionic Gonadotropin/pharmacology , Fertility/drug effects , Male , Organ Size/drug effects , Rats , Rats, Inbred Strains , Regional Blood Flow/drug effects , Spermatogenesis/drug effects , Testis/blood supply , Testis/cytologyABSTRACT
PIP: In 1972, gossypol was shown to have a potent antifertility effect in man. Further clinical trials indicated that in certain districts such as Nanjing, occasional cases of hypokalemia or even hypokalemic paralysis may occur during gossypol administration. There were contradictory views concerning the etiology and pathogenesis of this condition. The authors carried out a series of clinicopharmacologic observations on gossypol related hypokalemic patients. The occurrence of hypokalemic paralysis is far more frequent in gossypol takers than in the control population which suggests that gossypol may be a causative agent in the disorder. In addition other factors such as low dietary potassium may contribute to the development of hypokalemia. In these patients, total body postassium is low and 1 of the apparent causes of body potassium depletion is renal potassium loss not due to hyperaldosteronism. The use of potassium salt at the stage of fatigability, a sure prodromal symptom of impending hypokalemic paralysis, is effective in the prevention of paralysis but for final resolution of the problem, the authors believe that increase in the dietary potassium level or even modification of the gossypol molecule may be necessary. Observation of the urine/serum potassium ratio in high water diuresis may be helpful to the diagnosis of normokalemic potassium deficiency.^ieng
