1 The effect of oral doses of cromakalim 0.5, 1.0, 1.5 and 2.0 mg on several cardiovascular parameters was studied in healthy male volunteers. 2 In the first study, no dose of cromakalim reduced systolic or diastolic blood pressure in the supine or standing position. Reductions of diastolic blood pressure after exercise (P < 0.01) were observed 4 h after administration of 2.0 mg. 3 There was a trend towards increased heart rate after 2.0 mg at all time intervals, and significant changes were observed in supine and standing heart rate at 2 and 4 h (P < 0.01). No significant change was observed in exercise heart rate. 4 In the second study small increases in forearm blood flow were observed from 3 h to 5 h after oral administration of 1.0 and 2.0 mg of cromakalim. Forearm vascular resistance was significantly reduced after 2.0 mg (P < 0.025) when compared with placebo. No change was observed in forearm venous capacitance after either dose of cromakalim, or placebo. Supine heart rate was significantly increased 4 h after 2.0 mg of cromakalim (P < 0.025). 5These results show that oral administration of cromakalim decreases diastolic blood pressure and forearm vascular resistance. A hypotensive effect is probably attenuated by reflex tachycardia.

In 12 healthy volunteers who received orally 100, 200, 300, 400 and 600 mg mexiletine at weekly intervals, the maximum plasma concentration of mexiletine and AUC increased linearly with the dose of mexiletine. Between doses there were no significant differences in the values for clearance and volume of distribution of mexiletine but there were for plasma elimination half-life. These results indicate that the kinetics of mexiletine are linear.

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