Pharmacokinetics and hemodynamic effects of diltiazem in healthy volunteers: comparing resting with the effect of exercise.

Purpose: To determine the steady-state plasma concentrations of diltiazem (DTZ) and hemodynamic effect in humans at rest and during exercise. Methods: Healthy volunteers (10 F, mean age 22, and 11 M, mean age 24) were recruited. Prior to receiving DTZ, each volunteer performed two 3-minute stages of treadmill exercise according to the Bruce protocol. Intra-arterial BP and ECG recordings were obtained before, during and immediately post exercise. Each volunteer then received DTZ 60 mg qid for one week. The same exercise protocol was repeated I h after the last dose. Steady-state plasma concentrations of DTZ were determined by a previously reported HPLC. Results: DTZ decreased resting DBP from 84 ± 13 to 79 ± 10 mmHg (p > 0.05), and HR from 89±11 to 82 ± 13 bpm (p <0.05). During exercise, an average of 32 and 10% increase in SBP and DBP, respectively, and a 47% increase of HR was found (p < 0.05). DTZ limited these increases to 21% for SBP, 5% for DBP, and 44% for HR (p < 0.05 for drug effect). Steady-state plasma DTZ concentrations were 141 ± 56 ng/ml. Conclusion: DTZ significantly decreased resting HR but not BP in health volunteers. It decreased both hemodynamic variables during exercise. Thus, the hemodynmic effects of diltiazem are more profound during exercise, and may be more useful surrogate markers for calcium antagonists and other cardiovascular agents in healthy volunteer studies.