5-Fluorouracil was administered by continuous hepatic intra-arterial infusion to eight patients with the diagnosis of cancer of the gastrointestinal tract and hepatic metastases. Its elimination characteristics were investigated to see if they correlated with therapeutic effect or reduced clinical toxicity when the drug was given by this route. Urinary excretion of drug and metabolites was similar to findings after intravenous bolus doses. Disposition changes could not be correlated with therapeutic effect or clinical toxicity. A dose-related biphasic effect of 5-fluorouracil was found on circulating platelets. Doses greater than 6 mg kg-1 d-1 decreased the number of circulating platelets, while doses less than that resulted in an increase in circulating platelets. Further studies are required to determine the mechanism of the effect of 5-fluorouracil on platelets.

Adult↗

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Depression, EEG sleep, and clinical response.

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Adult↗

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Kinetic disposition and hemodynamic effects of tetrandrine in anesthetized dogs.

The kinetic disposition and hemodynamic effects ot tetrandrine, l3 mg/kg i.v., over 30 s were studied in five anesthetized dogs during continuous monitoring of the ECG and systemic arterial pressure. Repeated determinations of cardiac output (CO) and pulmonary capillary wedge pressure (PCWP) were made via a flow-directed thermodilution catheter in the pulmonary artery. Blood samples were drawn at intervals for determination of plasma tetrandrine or erythrocyte binding of the drug. Maximal reductions in mean and diastolic arterial pressures of 23 +/- 4% were observed within 5 min of the drug infusion without a change in systolic pressure. CO was increased maximally 52% and systemic resistance reduced 5l% at l0 min, gradually returning to baseline values in l-2 h. PCWP was increased transiently at 5-l0 min. The PR interval was prolonged slightly without alteration in the R-R interval, QRS, or QTc. Changes in MAP and PR interval were correlated significantly with plasma tetrandrine concentrations over time, which followed a two-compartment kinetic model with a distribution t1/2 of 7 min and an elimination tl/2 of 88 min. The apparent volume of distribution at steady state was 57 L/kg. Plasma tetrandrine was greater than 90% bound to plasma proteins, and approximately 44% of whole blood tetrandrine was associated with erythrocytes. Tetrandrine is a potent arteriolar vasodilator drug with slight effects on AV conduction, but without significant negative inotropic effects in anesthetized dogs.

Alkaloids↗

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