Pharmacokinetics of amlodipine in hypertensive patients undergoing haemodialysis

Objective. Amlodipine is a calcium antagonist of the dihydropyridine class. This study was performed to examine the single and multiple dose pharmacokinetics of amlodipine in hypertensive patients undergoing haemodialysis and to measure the index of accumulation during multiple dosage. An additional objective was to examine the dialysability of amlodipine by measuring its appearance in dialysate. Methods. Seventeen hypertensive out-patients on haemodialysis were enrolled in this prospective, open, non-comparative phase-IV study. Fifteen patients completed the study. In the first part of the study, the patients were given a single oral 5-mg dose of amlodipine and blood samples taken 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 72 and 144 h later. After a 4-week wash-out period, the patients were given a daily 5-mg oral dose of amlodipine for 30 days. The trough levels of amlodipine were measured on days 8, 15, 22 and 29. On day 30, the total time course of amlodipine concentrations in plasma was measured, as in the first part of the study. In addition, on day 15, the concentrations of amlodipine in dialysate were measured at the same time as in blood. Blood pressure and heart rate were measured and adverse events monitored. Pharmacokinetic parameters [C-max, t(max), k(el) and AUC(0-24)] were calculated for the single dose and for the dose on day 30 and the accumulation index calculated on the basis of AUC(0-24) and C-max. Results. The mean values of the single-dose pharmacokinetic parameters were as follows: C-max 3.83 mug <LF>l(-1), t(max) 5.01, AUC(0-24) 59.90 mug l(-1) h, k(el) 0.0177 h(-1). The mean accumulation index on the basis of AUC(0-24) was calculated as 3.70. Very low levels of amlodipine were detectable in dialysate fluid. The most frequently reported adverse events were hypertension, hypotension and muscle cramps. Conclusion. There are only minor differences in the pharmacokinetics of amlodipine between healthy subjects and hypertensive patients on haemodialysis. Comparison with literature values for healthy volunteers suggests that amlodipine is rapidly and extensively absorbed in the patient group. Amlodipine is essentially not dialysable. These findings do not indicate a need for dose adjustment in renal failure patients on haemodialysis.