THE PHARMACOKINETICS OF MEPERIDINE IN THE MYOCARDIUM OF CONSCIOUS SHEEP

The pharmacokinetics of meperidine in blood and myocardium were studied in five conscious sheep. After an intravenous (IV) bolus of 100, 200, or 300 mg meperidine HCl, the maximum arterial blood concentrations (mean +/- SD) were 27.8 +/- 4.6, 66.8 +/- 13.3, and 114.5 +/- 23.1 mu g/mL, respectively, and coronary sinus blood concentrations were 2.7 +/- 1.0, 7 +/- 1.5, and 13.7 +/- 2.5 mu g/mL, respectively. These were linearly related to dose. Net uptake of meperidine into the myocardium occurred during the first minute and the maximum rates of uptake (influxes) were 5.1 +/- 2.6, 15.1 +/- 4.6, and 27.5 +/- 8.7 mg/min. Myocardial meperidine concentrations, calculated using mass balance principles for the 100-, 200-, and 300-mg doses, respectively, were 9.0 +/- 1.8, 20.5 +/- 8.6, and 34.1 +/- 7.4 mu g/g at peak and had decreased to 57% +/- 11% of peak 5 min after injection. No pseudoequilibrium between blood and myocardial meperidine concentrations had been reached within the 15-min study period, Myocardial perfusion and blood-myocardial concentration gradients were both important determinants of meperidine myocardial pharmacokinetics. The fast uptake and brief sojourn of meperidine in the myocardium agreed with its rapid but transient negative inotropic effect reported previously.