Biomedical subjects
Publications and source records attributed to M B Bottorff.
A patient with chronic renal failure who experienced symptomatic ventricular tachycardia was treated successfully with procainamide (PA) after numerous dosage adjustments to optimize his clinical response and serum PA and NAPA concentrations. Efforts to maintain total combined serum levels at 20-30 micrograms/ml led to sustained ventricular ectopy whenever the serum PA levels decreased to less than 8 micrograms/ml.
High pressure liquid chromatography (HPLC) and fluorescence polarization immunoassay (FPIA) were compared in a quinidine pharmacokinetic study. Six healthy male subjects received single oral doses of regular release (RR) quinidine sulfate, sustained release (SR) quinidine bisulfate and the same dose of the SR product with food (SR-F). Serum was collected for 49 h after each dose and analysed for quinidine by HPLC and FPIA. Using HPLC, there were no statistically significant differences between dosing regimens with respect to area under the curve (AUC) or terminal rate constant (K). The RR dose resulted in a higher peak plasma concentration (Cp) and shorter time to peak (Tp) than either of the SR doses (p less than 0.01). Food had no apparent effect on the bioavailability of the SR product. When using FPIA, food administration was found to increase the AUC for the SR product (p less than 0.05) and all three dosage regimens resulted in a different Cp and Tp (p less than 0.001). When comparing all pharmacokinetic parameters determined by each assay, FPIA resulted in a significantly lower K (p less than 0.01). Orthogonal regression of all serum quinidine concentrations showed that FPIA = 0.926 (HPLC) + 0.06 (r = 0.971, p less than 0.001). Analysis of quinidine concentrations in different concentration ranges revealed that FPIA overestimated HPLC for concentrations less than 1 micrograms ml-1 (p less than 0.001) and underestimated HPLC for concentrations greater than 2 micrograms ml-1 (p less than 0.01). Although the use of FPIA is appropriate for quinidine therapeutic drug monitoring, HPLC is the preferred assay method for assessing pharmacokinetic parameters in single dose bioavailability studies.
Amrinone is the first noncatecholamine inotropic agent with substantial vasodilating properties to be approved by the Food and Drug Administration. Its use in acute congestive heart failure (CHF) is associated with significant increases in cardiac index, reductions in pulmonary capillary wedge pressure and systemic vascular resistance and little or no change in mean arterial pressure. Pharmacokinetic studies of amrinone report an elimination half-life of 2.6-8.3 hours, with slower elimination more likely in patients with compromised renal or hepatic function. Intravenous bolus doses of 0.75-3.5 mg/kg followed by infusions of 5-20 micrograms/kg/min produce hemodynamic improvements similar to those with dobutamine. Side effects with amrinone therapy are usually mild, but thrombocytopenia occurs in 2.4% of patients. Amrinone appears equally as efficacious as dobutamine in the management of acute CHF, but its role in therapy depends on efficacy and side effect data in greater numbers of patients.
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