ABSTRACT
The pharmacological effect of 6-deoxyclitoriacetal (6-DA), a rotenoid compound isolated from the roots of Clitoria macrophylla Wall. (Papilionaceae), was examined on different smooth muscle preparations. 6-Deoxyclitoriacetal 0.2 mg/ml produced a significant decrease in the spontaneous contraction of isolated rat uterus. It also suppressed the contraction induced by acetylcholine 5x10(-6) M and oxytocin 5x10(-3) IU/ml. The cumulative contractile responses of rat aortic strips caused by serotonin 10(-8)-10(-4) M and norepinephrine 10(-11)-10(-7) M were reduced by 6-DA 0.4 mg/ml. In calcium free Kreb's solution, 6-DA inhibited the aortic contraction produced by a cumulative dose of calcium chloride (0.1-30 mM). In guinea-pig ileum, 6-DA 0.15 mg/ml exerted the spasmolytic activity by inhibition of the contractile response evoked by various contractile agents e.g. acetylcholine 10(-9)-10(-5) M, serotonin 10(-9)-10(-5) M and histamine 10(-9)-10(-5) M. All of the results indicated that 6-DA could induce a smooth muscle relaxant effect by interference with intracellular calcium metabolism.
Subject(s)
Muscle Relaxation/drug effects , Muscle, Smooth/drug effects , Rotenone/pharmacology , Animals , Cells, Cultured , Dimethyl Sulfoxide/pharmacology , Dose-Response Relationship, Drug , Female , Guinea Pigs , Ileum/drug effects , Ileum/physiology , In Vitro Techniques , Male , Muscle, Smooth/cytology , Muscle, Smooth, Vascular/drug effects , Probability , Rats , Rats, Wistar , Reference Values , Rotenone/analogs & derivatives , Sensitivity and Specificity , Uterus/drug effects , Uterus/physiologyABSTRACT
The effect of antacid on aspirin pharmacokinetics and bioavailability was determined in 10 healthy adult male and female volunteers, aged 20-45 years old. Each subject received 650 mg of aspirin orally after an overnight fast. The wash out period was 14 days and then all subjects were given 650 mg of aspirin 10 minutes after antacid (aluminium hydroxide and magnesium hydroxide). Plasma aspirin, salicylate and salicyluric acid levels were determined by a specific high performance liquid chromatographic analysis. Individual plasma profiles were analysed using compartmental and non-compartmental methods. The results show that antacid affected the relative bioavailability of aspirin since the mean peak concentration (Cmax) of aspirin was significantly higher when antacid was given. However, the time to reach peak concentration (Tmax) and the area under the plasma concentration-time curve (AUC) showed no significant difference between the two treatments. It was, therefore, not possible to conclude that the non-bioequivalence was caused by a difference in rate or amount of aspirin absorption, or both. No significant difference was observed in Cmax, Tmax, AUC, t1/2, Ka, Kel of salicylate and salicyluric acid. However, the rate of total salicylate absorption was increased since the absorption rate constant (Ka) was higher when antacid was given. This may provide a more rapid effect of the drug.
