The pharmacokinetics of
diltiazem and its major metabolites,
deacetyldiltiazem and N-monodemethyl-
diltiazem, were studied after single and chronic
oral administration in eight patients aged 45 to 69 years with
unstable angina pectoris, treated by
diltiazem, 120 mg t.i.d. After a single oral dose the time to peak plasma
diltiazem concentration was 3.4 (2.1 to 5.0) hours and the elimination half-life was 6.6 hours (4.4 to 10.8 hours). These were unchanged after repeated
oral administration (16 to 19 doses). The mean trough (8 hours after administration) plasma
diltiazem level after six consecutive doses was 167 micrograms/L (63 to 286 micrograms/L) and was thereafter stable. With chronic administration the AUC increased by
a factor of 2.24 +/- 0.31 (SEM; P less than 0.01).
Plasma protein binding of
diltiazem in these patients ranged from 83% to 93% whereas
deacetyldiltiazem binding ranged from 58% to 75%.
Plasma protein binding was independent of
drug concentration and
duration of treatment. Thus an average dose of 120 mg
diltiazem given every 8 hours would appear to be a suitable regimen of treatment in most patients with
angina pectoris, although users should be aware that there is a significant interpatient variability in steady-state
diltiazem concentrations and that a significant accumulation of
diltiazem occurs with chronic
therapy.