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The disposition of a single oral dose of diltiazem hydrochloride was studied in six male patients treated by continuous ambulatory peritoneal dialysis. Peak concentrations were obtained 2 to 4 hours postdose. The mean absorption rate constant was 0.94 +/- 0.21 (sd) hr-1, and the mean elimination half-life was 3.09 +/- 1.16 hr. Serum levels of deacetyldiltiazem, a metabolite of diltiazem, were always below 10 ng/mL. The amounts of diltiazem and deacetyldiltiazem eliminated in dialysate over 24 hours represent less than 0.1% of the administered dose. The pharmacokinetic parameters of diltiazem determined in these patients did not differ from those determined in healthy volunteers and in patients suffering from end-stage renal disease.

The effect of advancing age on the kinetics of the antiarrhythmic agent mexiletine was studied by comparing various kinetic parameters calculated after administration of a single oral dose of mexiletine hydrochloride to seven elderly and eight young healthy volunteers. The rate of absorption of the drug from the gastrointestinal tract was significantly slower in the elderly (1.37 +/- 0.51 hr-1) than in the young group (2.25 +/- 0.79 hr-1). The mean values for elimination half-life and oral clearance were 12.3 +/- 3.7 hr and 10.3 +/- 5.4 mL/min/kg respectively in the young group and 14.4 +/- 4.5 hr and 8.5 +/- 2.9 mL/min/kg respectively in the elderly group. Neither of these parameters was significantly different between the two groups. The amount of mexiletine eliminated in urine up to 48 hours postdose was identical in both groups and represented less than 5% of the administered dose. It is concluded that the age-related modifications in the kinetics of mexiletine are not clinically important during chronic administration of the drug.