The physiological pharmacokinetic model developed in rats predicts thiopental pharmacokinetics in humans. Differences in basal cardiac output may explain much of the variability in early thiopental disposition between subjects.

No abstract

Verapamil disposition was studied in 12 patients with chronic and fibrillation. After an intravenous bolus of 15 mg plasma concentration was determined and the data fit in a three-compartment model. Model independent parameters were calculated and values for half-life (t 1/2), clearance, and steady-state distribution volume were 6.3 +/- 4 hr, 13.3 +/- 7.7 ml/min/kg, and 4.3 +/- 1.9 l/kg. The model was used to design a multistep infusion scheme, which was employed successfully to achieve predetermined plasma concentrations. Following single oral doses of 120 mg, plasma levels of verapamil and norverapamil were determined. The elimination t 1/2 for verapamil and norverapamil were 8.3 +/- 6.1 and 10.5 +/- 5.6 hr, respectively. The bioavailability of oral verapamil was 35 +/- 16%. During long-term oral therapy the mean verapamil plasma concentration was twice the value predicted from the single-dose studies. This suggests that verapamil may have reduced clearance during long-term oral use.

The disposition of lidocaine and penicillin was studied in normal subjects before and after 7 days of total recumbency. Penicillin (1,000,000 U) and lidocaine (100 mg) were administered intravenously. Lidocaine protein binding was also followed. Total body clearance, elimination half-life, and volume of distribution were calculated. There were no statistically significant differences in these disposition parameters before and after 7 days of recumbency. The binding of lidocaine also was not changed after bed rest. We conclude that the physiologic changes that occur during prolonged bed rest do not affect distribution or elimination of lidocaine or penicillin.