Comparative efficacy, safety and pharmacokinetics of verapamil SR vs verapamil IR in hypertensive patients

Abstract

The antihypertensive effects of the regular immediate release formulation of verapamil (verapamil IR) and the newer sustained release formulation of verapamil (verapamil SR) were compared in Hispanic patients with untreated essential hypertension. Verapamil IR was given in 3 divided doses (80 or 160mg 3 times daily) and verapamil SR was given either as a single daily dose of 240mg or as 240mg every 12 hours. With both formulations there was a significant reduction in systolic (SBP) and diastolic blood pressure (DBP); a greater lowering of BP was observed with verapamil 480 mg/day than with 240 mg/day. With verapamil SR 480 mg/day, 91% of patients had reductions in SBP and DBP greater than 20 and 15mm Hg, respectively. In addition, 83% of patients reached normotension. With the lower dose (240mg once daily), 83% of patients had decreases in DBP greater than 10mm Hg and 73% of patients achieved normotension. Comparable effects were achieved with verapamil IR. With verapamil IR there was a more rapid fall in BP which peaked 3 to 4 hours postdose, whereas with verapamil SR a more gradual and sustained BP reduction was observed. Only small changes in heart rate (HR) were observed with verapamil IR and verapamil SR. For verapamil SR, the mean increase in HR was 5 beats/min (to 80 beats/min) and the mean decrease in HR was 13 beats/min (to 62 beats/min). Both verapamil SR and verapamil IR prolonged the PR interval of the ECG. An equal degree of PR prolongation was observed with 240 and 480 mg/day. The incidence of side effects (headache, palpitations, dizziness and flushing) was dose dependent, decreased with continuous treatment and was much higher with verapamil IR than with verapamil SR. Steady-state plasma verapamil concentrations were monitored. Compared with verapamil IR, verapamil SR produced a more gradual rise and a more sustained elevation of plasma verapamil and norverapamil concentrations. Comparable trough verapamil concentrations (Cmin) were observed with verapamil IR (98 micrograms/L) and SR (81 micrograms/L); morning Cmin verapamil concentrations were higher than daytime Cmin values. The normalised area under the plasma concentration-time curve (AUC) and maximum concentration (Cmax) were 10 to 20% greater for verapamil IR than SR. The 2-fold increase in oral dose produced a 2.2- and 2.4-fold increase in AUC for verapamil IR and SR, respectively, associated with a 20% reduction in metabolism to norverapamil. Fasting increased the rate and extent of absorption of verapamil.(ABSTRACT TRUNCATED AT 400 WORDS)