The effect of a single oral dose of ethanol on hepatic blood flow in man.

The magnitude and time course of changes in hepatic blood flow following oral ingestion of a single (0.6 g/kg) dose of ethanol was studied using the model compound indocyanine green (ICG). Hepatic blood flow was not significantly different at 40, 90, 150 and 210 minutes following ethanol as compared to baseline values measured 20 and 70 min prior to alcohol ingestion. These results suggest that ethanol, at concentrations commonly associated with social drinking, has minimal effects on liver blood flow and would be expected to contribute little to changes in either the bioavailability or clearance of drugs highly extracted by the liver.

Hematological effects associated with beta-lactam use.

Beta-lactam antibiotics have continued to be the mainstay of antiinfective treatment. Newer agents, such as the third-generation cephalosporins or ureidopenicillins, have the advantage of a broader antimicrobial spectrum and improved pharmacokinetics. The beta-lactams are often promoted as alternatives to more toxic antibiotic regimens. However, several of the beta-lactams have been shown to produce hematological effects, some of which can be life threatening. The primary hematological effects appear to be inhibition of normal platelet function and the coagulation cascade, which is reflected by changes in bleeding times and increases in prothrombin time and activated partial thromboplastin time, respectively. Although not all patients will develop bleeding problems associated with these agents, close monitoring of patients with risk factors for bleeding and dosage adjustments may help to avert these drug-induced hematological problems.

Kinetics of meperidine N-demethylation in the perfused rat liver preparation.

Meperidine and normeperidine elimination was studied in the once-through perfused rat liver preparation. Biliary excretion of these bases was minimal, and nonlinear metabolism of meperidine (extraction ratio of 1.0 to 0.89 at 1 to 19 micrograms/ml) and normeperidine (extraction ratio of 0.6 to 0.1 at 1 to 25 micrograms/ml) was observed when input concentration was increased. The rate of efflux of normeperidine in hepatic venous blood represented an increasing proportion of the rate of presentation and the rate of loss of meperidine (34 to 92%) at increasing meperidine input concentration. But when the data were corrected for the nonlinear sequential metabolism of normeperidine, the rate of N-demethylation accounted completely for the rate of metabolism of meperidine. These N-demethylation rates obeyed Michaelis-Menten behavior, and appeared to be saturated at input meperidine concentration greater than 5 micrograms/ml.