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 recruit ed. 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 1 h after the last dose. Steady-state plasma concentr ations of DTZ were determined by a previously reported HPLC. Results: DTZ d ecreased resting DBP from 84 +/- 13 to 79 +/- 10 mmHg (p > 0.05), and HR fr om 89 +/- 11 to 82 +/- 13 bpm (p < 0.05). During exercise, an average of 32 and 10% increase in SEP and DBP, respectively, and a 47% increase of HR wa s found (p < 0.05). DTZ limited these increases to 21% for SEP, 5% for DBP, and 44% for HR (p < 0.05 for drug effect). Steady-state plasma DTZ concent rations were 141 +/- 56 ng/ml. Conclusion: DTZ significantly decreased rest ing HR but not BP in health volunteers. It decreased both hemodynamic varia bles during exercise. Thus, the hemodynmic effects of diltiazem are more pr ofound during exercise, and may be more useful surrogate markers for calciu m antagonists and other cardiovascular agents in healthy volunteer studies.