Age and gender related changes in stereoselective pharmacokinetics and pharmacodynamics of verapamil and norverapamil.

Abstract

1 Pharmacokinetics and pharmacodynamics of R-and S-verapamil and R-and Snorverapamil were studied at steady state following administration of 180 mg verapamil delivered by a controlled-release gastrointestinal therapeutic system (COER-verapamil). 2 Of the 30 young (19 to 43 years) and 30 elderly subjects (65 to 80 years) enrolled, approximately half of each age group were women; all subjects were healthy and none were smokers.3 Mean R-and S-verapamil and R-and S-norverapamil Cmax, Cmin, and AUC values for elderly subjects were 1.2 to 2.2 times greater than those for young subjects; these differences were statistically significant at P < 0.05. Median tmax values for young and elderly subjects were not significantly different for any enantiomer. The mean half-life values of R-and S-verapamil for elderly subjects were approximately 20 h compared with approximately 13 h for young subjects, respectively. The mean half-life values of R-and S-norverapamil for elderly subjects were approximately 31 h and 20 h, respectively, compared with approximately 19 h and 21 h for young subjects, respectively. 4 In both age groups, the mean plasma verapamil concentrations of each enantiomer were higher for women than for men at all time points. 5 Mean arterial pressure (MAP) had a significant correlation to R-(r2 = 0.86) and S-verapamil (r2 = 0.87) concentration values that was not influenced by either gender or age of the patient. Change in PR-interval also had a significant correlation to R-and S-verapamil concentration values. However, the sensitivity of the response to changes in R-and S-verapamil concentration values in elderly subjects was about 1/5 of that in younger subjects.

Gender medicine: a task for the third millennium

“…Weight-normalized verapamil clearance (CYP3A4 metabolized but also Pgp substrate/inhibitor) is as much as 50% greater in older women than in older men [ 28 ]. Another interesting example is the case of β -blockers.…”

“…However, another study that examined sex-based pharmacokinetic differences for oral verapamil showed that the reduction in mean arterial blood pressure owing to the drug was closely correlated with its plasma concentration, although without any interaction by sex [ 28 ]. Women had a higher response rate and a major decrease in blood pressure with amlodipine, compared with men [ 45 ].…”

Treatment of Elderly Hypertensive Patients With a Delayed‐Release Verapamil Formulation in a Community‐Based Trial

“…It lowers SBP and DBP and is capable of achieving target BPs in a majority of patients when given as monotherapy. Its high efficacy in treating BP in older patients may be at least partly due to differences in the pharmacokinetics of the drug among age groups, in particular higher maximum concentrations and slower clearance from the plasma in elderly patients 23 ; however, these changes do not appear to increase the risk of adverse events. The CODAS-verapamil formulation may be especially beneficial in elderly patients with hypertension because it delivers peak concentrations of verapamil between 6 a.m. and noon to coincide with morning BP surge, a period during which there is an increased incidence of cardiovascular and stroke events in these vulnerable people.…”

The effect of gender on the pharmacokinetics of verapamil and norverapamil in human

“…Verapamil is a calcium ion influx inhibitor, having antiarrhythmic, antianginal and antihypertensive properties [4]. Verapamil undergoes extensive first-pass metabolism and is both a cytochrome P450 and P-glycoprotein substrate [3], so it is expected that the pharmacokinetic parameters may be different between the two genders.…”