Comparative Efficacy, Safety and Pharmacokinetics of Verapamil SR vs Verapamil IR in Hypertensive Patients
- 14 Downloads
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 μg/L) and SR (81 μg/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. This effect was manifested by increases in peak: trough ratios, higher Cmax values, greater AUCs and shorter time to maximum concentration. Fasting increased norverapamil concentrations but did not modify verapamil: norverapamil ratios. In summary, verapamil SR may be substituted for verapamil IR on a milligram to milligram basis. The single or twice-daily administration of verapamil SR simplifies treatment and reduces side effects. Hispanic patients with hypertension had an excellent BP response to treatment with verapamil.
Unable to display preview. Download preview PDF.
- Albernethy DR, Schwartz JB, Todd EL, Luchi R, Snow E. Verapamil pharmacodynamics and disposition in young and elderly hypertensive patients. Annals of Internal Medicine 105: 329–336, 1986Google Scholar
- Brugmann U. Calcium antagonists in hypertension and coronary heart disease: results from a double-blind, randomized, placebo-controlled study with verapamil SR 240 mg. In Fleckenstein A, Laragh JH (Eds) Hypertension–the next decade: verapamil in focus, pp. 106–113, Churchill Livingstone, Edinburgh, 1987Google Scholar
- Cubeddu LX. Racial differences in response to antihypertensive drugs: a focus on verapamil. Journal of Clinical Hypertension 3: 72S–78S, 1986Google Scholar
- de Faire U, Forslund L, Andersson P, Bondesson V, Hedbacl B, et al. The antihypertensive effect of verapamil in twice and thrice daily dose regimens. Subanalysis of 24 h blood pressure profiles. In Fleckenstein A, Laragh JH (Eds) Hypertension–the next decade: verapamil in focus, pp. 351–353, Churchill Livingstone, Edinburgh, 1987Google Scholar
- Kingma JH, Bernink PJLM, van Gilst WH, Kerkkamp HJJ, Wesseling H. Comparison of instant and slow release verapamil in patients with hypertension and coronary artery disease. In Fleckenstein A, Laragh JH (Eds) Hypertension–the next decade: verapamil in focus, pp. 250–253, Churchill Livingstone, Edinburgh, 1987Google Scholar
- Kirsten EB, Guerrero J, Müller-Peltzer. Pharmacokinetics of verapamil slow release formulation. In Fleckenstein A, Laragh JH (Eds) Hypertension–the next decade: verapamil in focus, pp. 274–279, Churchill Livingstone, Edinburgh, 1987Google Scholar
- Koike Y, Shimamura K, Shudo I, Saito H. Pharmacokinetics of verapamil in man. Research Communications in Chemistry, Pathology and Pharmacology 24: 37–47, 1979Google Scholar
- Midtbo KA, Hals O, Lauve O. A new sustained-release formulation of verapamil in the treatment of hypertension. Journal of Clinical Hypertension 3: 125S–132S, 1986Google Scholar
- Veterans Administration Cooperative Study Group on Antihypertensive Agents. Comparison of propranolol and hydrochlorothiazide for the initial treatment of hypertension. I. Results of short term titration with emphasis on racial differences in responses. Journal of the American Medical Association 248: 22–29, 1982aCrossRefGoogle Scholar
- Veterans Administration Cooperative Study Group on Antihypertensive Agents. Racial differences in response to low-dose captopril are abolished by the addition of hydrochlorothiazide. British Journal of Pharmacology 14: 975–1015, 1982bGoogle Scholar