Quinidine-induced rise in ajmaline plasma concentration

A high-performance liquid chromatographic method is described for the simultaneous determination of ajmaline and quinidine in human plasma. With 0.5 ml plasma sample of a ajmaline and quinidine, concentrations as low as 0.001 and 0.01 micrograms ml-1, respectively, could be detected and the technique could be used to investigate the effect of quinidine on the pharmacokinetics of ajmaline. Four healthy subjects were given oral ajmaline (50 mg) alone or in combination with quinidine sulphate (200 mg) on separate occasions. When ajmaline was administered alone, its plasma concentrations were less than 0.03 micrograms ml-1. Quinidine induced a marked increase to give a mean peak concentration of ajmaline which increased from 0.018 micrograms ml-1 after a single administration to 0.141 micrograms ml-1 in combination with quinidine. the area under the ajmaline concentration-time curves was increased 10 to 30-fold by the concurrent administration of quinidine. According to the one compartment open model, the absorption rate constant of ajmaline did not change appreciably, but the elimination rate constant was reduced to approximately 50% of the value in the absence of quinidine. The results indicate the existence of a significant interaction between oral ajmaline and quinidine.