ABSTRACT
Calcium salts have been recommended for and used in the treatment of various forms of cardiac arrest for many years. Although calcium plays a major role in excitation-contraction coupling, it can have a deleterious effect in some processes of cellular injury. Clinical trials suggest that calcium salts are not effective in ventricular fibrillation and asystole, but that some patients with electromechanical dissociation may have a favorable hemodynamic response. Because of the potential risks of calcium salts, their use should be limited to specific subsets of patients with cardiac arrest.
Subject(s)
Calcium/therapeutic use , Heart Arrest/drug therapy , Animals , Calcium/physiology , Humans , Myocardial Contraction/drug effects , ResuscitationABSTRACT
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.
Subject(s)
Blood Platelets/drug effects , Fluorouracil/metabolism , Liver Neoplasms/drug therapy , Adult , Aged , Female , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Hepatic Artery , Humans , Infusions, Intra-Arterial , Male , Middle Aged , Time FactorsABSTRACT
A high-pressure liquid chromatographic method that is used to determine the pharmacokinetic disposition of 5-fluorouracil from the plasma compartment is presented. The method requires only 0.5 ml of plasma for each determination and is sensitive to 0.1 mg of drug per liter. Novel methodology with the use of an ion-specific electrode technique for the determination of urinary excretion kinetics of 5-fluorouracil and its metabolites is also presented. This study demonstrated a much greater variability for the disposition of 5-fluorouracil by cancer patients than has been reported previously. The apparent volume of distribution for this drug varied more than 37-fold. Its plasma half-life varied more than 19-fold, and its urinary excretion half-life varied almost 400-fold. These data are compatible with the hypothesis that this variation could account, at least in part, for the variable therapeutic and toxic response to 5-fluorouracil. The methodology presented in this study is sufficiently simple and sensitive to allow assessment of this hypothesis by investigating cancer patients who receive therapeutic doses of 5-fluorouracil.
