ABSTRACT
A combination of 3H-labelled oestriol (OE3) and 14C-labelled oestriol-16-glucosiduronate (OE3-16Gl) was infused over 6 hours to two women at midpregnancy. The urinary metabolites were isolated, quantitated and identified. Some 90% of the tritiated and about 98% of the 14C-labelled material administered was recovered from urine specimens collected for 48 hours.
About 63% of the 3H-labelled material recovered was found to be OE3-16Gl, some 29% oestriol-3-glucosiduronate (OE3-3Gl), approximately 5% oestriol-3-sulphate-16-glucosiduronate (OE3-3S,16Gl) and about 3% oestriol-3-sulphate (OE3-3S). From the 14C-labelled material recovered, approximately 72% was isolated as OE3-16Gl, about 25% as OE3-3Gl, some 3% as OE3-3S,16Gl and only a minute portion was found to be OE3-3S. No unconjugated labelled material was found to be excreted. All the 3H- and 14C-labelled material isolated as OE3-16Gl was identified as such; no oestriol-17-glucosiduronate could be detected.
The urinary excretion of endogenous oestriol conjugates also was measured and found to vary over 24 hours. Their per cent distribution agreed well with that of the 3H-labelled conjugates in both cases.
This study confirms and completes our previous studies on OE3-16Gl, OE3-3S, OE3-3Gl and OE3-3S,16Gl metabolism in pregnant women. A scheme is presented, delineating the quantitative aspects of OE3 metabolism. The data indicate that circulating OE3-16Gl is formed from circulating OE3 at 77% of the rate at which OE3 enters the circulation. The urinary excretion rate of circulating OE3-16Gl was calculated to be 55% of its rate of entry into the circulation. These findings suggest that renal clearance mechanisms, rather than the rate of 16-glucosiduronation, are a rate limiting factor in the disposition of oestriol in pregnancy.
Multiple Linear Regression Modeling To Predict the Stability of Polymer–Drug Solid Dispersions: Comparison of the Effects of Polymers and Manufacturing Methods on Solid Dispersion Stability
