Kinetics of pharmacological effect of diltiazem in spontaneous hypertensive rats

The kinetics of intravenous (i.v.) infusion of diltiazem was studied in spontaneous hypertensive rats (SHR) at three dose levels (1, 2 and 4 mg/kg/30 min). Apparent clearance values (Cle) were obtained from the decline of diltiazem hypotensive effect through a model based on the relationship R vs. log dose. For each dose level there were no significant differences between apparent Cle values and real Cl values obtained from plasmatic concentrations at 25 min after infusion (Cl25). However, for both groups of data, Cl values increased with dose. For each level of perfused dose, Cl25 values were significantly higher than clearance values obtained after i.v. bolus administration of 3 mg/kg (Cliv).