Stanley L. Wallace

Colchicine plasma levels: Implications as to pharmacology and mechanism of action

Abstract A new method for quantitating colchicine in plasma is described, and plasma levels after administration in conventional therapeutic doses are reported in four groups of patients. In the first group the patients had normal renal and hepatic function and were not hyperuricemic. The second group was composed of patients with gout, the third of patients with severe renal disease and the fourth of patients with severe hepatic disease. The mean fifteen minute colchicine concentration in all groups was 1.14 ± 0.85 μg per 100 ml of plasma; the mean concentration at extrapolated zero time was 1.92 μg per 100 ml of plasma. In the patients with liver disease plasma colchicine concentrations were high and disappearance of the drug was rapid, whereas in the patients with gout and those with severe renal disease plasma concentrations were similar to those in the first group, but disappearance rates were slower. In vitro studies of others have shown that colchicine affects many leukocyte functions. Migration of polymorphonuclear leukocytes toward a chemotactic source was the only leukocytic activity affected by colchicine concentrations in the range of those found in the plasma of these patients.

Hypertriglyceridemia in Gout

Serum triglyceride levels were significantly higher in 34 patients with gout (42 mg. per 100 ml.) in comparison to the levels in 28 healthy men over 35 years of age (100 mg. per 100 ml.). There was no significant predictive relation between levels of serum uric acid and triglycerides in either group. No significant difference in serum cholesterol levels nor lipoprotein profile was apparent between the two groups. The patients with gout had been selected to exclude any manifestations of atherosclerosis or other disease known to be associated with abnormalities in circulating lipids. The results provide support for possible linkage of genetic factors influencing uric acid and triglyceride metabolism. The presence of hypertriglyceridemia in gout may be correlated with the increased incidence of arteriosclerosis.

Purification of colchicine, its photoisomer(s), and some congeners by paper and thin-layer chromatography

Abstract Four paper and four thin-layer chromatographic systems were studied for their ability to separate colchicine from its photoisomer(s) and other congeners. The best thin-layer systems were found to be chloroform: acetone:diethylamine (5:4:1) and chloroform:diethylamine (9:1) on silica gel. The most useful paper chromatographic systems were found to be benzene:acetic acid:water (10:4:10) and benzene:hexane:acetic acid:water (6:4:3:7) run for 4 hours. The importance of identifying and quantitating the light-induced degradation products of colchicine in radioisotopic studies on the metabolic fate of this drug in the human subject was stressed in these studies. The methods described were used to provide rapid and reproducible techniques for the measurement of colchicine in plasma, urine, and white blood cells.