The Lambeth Conventions are guidelines intended to be of practical value in the investigation of arrhythmias induced by ischaemia, infarction, and reperfusion. They cover the design and execution of experiments and the definition, classification, quantification, and analysis of arrhythmias. Investigators are encouraged to adopt the conventions in the hope that this will improve uniformity and interlaboratory comparisons.
The pharmacokinetics of a novel praziquantel preparation (Distocide) were investigated in Sudanese patients with hepatosplenic schistosomiasis and in healthy volunteers, and compared with those of Biltricide. The results of the first study indicated greater (P less than 0.05) plasma concentrations of Biltricide at 1.5, 2, 3 and 5 h after administration than with Distocide; plasma elimination half-lives (t 1/2) were not significantly different. In patients with hepatosplenic schistosomiasis, higher plasma levels of Distocide were noted (P less than 0.05 at 8 h) compared to healthy controls; however, due to wide inter-individual variations, there were no significant differences in maximum plasma concentration, time to maximum plasma concentration, area under the plasma concentration curve (AUC), volume of distribution, or clearance; t 1/2 was greater (P less than 0.05) in patients (11.9 +/- 5.4 h) than controls (2.3 +/- 0.4 h). In the presence of food, higher plasma concentrations of Distocide occurred compared to the fasting state; AUCs were greater (P less than 0.01) in both food groups, although the values of t 1/2 were shorter. The lower plasma levels and longer duration of action of Distocide may be advantageous in reducing side effects and prolonging exposure of the schistosomes to the drug.
Resolution of mexiletine enantiomers from the racemic mixture has been achieved by fractional crystallization through the formation of diastereoisomeric p-toluoyl tartrate salts. Following three crystallization steps in methanol, R-(-)- and S-(+)-mexiletine were resolved with an optical purity greater than 98% (yield approximately 30%) and their hydrochloride salts formed. Incremental doses of mexiletine enantiomers were administered to dogs with experimentally-induced arrhythmias to investigate the stereoselective antiarrhythmic and electrophysiological effects of these compounds. Using up to three extrastimuli, programmed electrical stimulation was performed in conscious animals 7-30 days after coronary ligation. R-(-)-Mexiletine prevented ventricular tachycardia in 3/6 dogs (2 after 0.5 mg kg-1, 1 after 8 mg kg-1); two animals died after 1 and 8 mg kg-1, respectively; one remained unchanged even at the highest dosage (16 mg kg-1). S-(+)-Mexiletine prevented ventricular tachycardia in only one dog (after 1 mg kg-1); two died after 4 and 8 mg kg-1, respectively; 2/5 remained unchanged even after the administration of 16 mg kg-1. No significant changes in any electrocardiographic intervals (PR, QRS, QTc) or refractory periods were induced by mexiletine enantiomers at any doses used (0.5-16.0 mg kg-1). These results suggest that R-(-)-mexiletine possesses greater antiarrhythmic properties than the opposite enantiomer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.