Placental transfer of radioactive C 14 -digitoxin was investigated in four pregnant women. The concentration of the labeled drug and its metabolic products in the various fetal organs was determined. Less than 1 per cent of the administered glycoside was detected in the fetus as unchanged digitoxin and less than 3.5 per cent as its metabolites. The fetal heart and kidney of 11 to 12 weeks gestation had the highest concentrations. However, at near term the fetal liver, gallbladder and intestine had somewhat similar concentrations. Metabolic conversion of the cardiac glycoside by fetal liver as well as biliary excretion is indicated from the tissue distribution data.

Venning and Browne! described a method for the isolation of sodium pregnanediol glucuronidate in the urine and theorized that this chemical substance represented the end-product in the metabolism of progesterone. Further studies confirmed the relationship of pregnanediol excretion to the luteal phase of the ovarian cycle and to normal pregnancy. Furthermore, a correlation between the administration of progesterone and the excretion of pregnanediol has been established although in the non-pregnant individual only a small fraction of progesterone administered can be recovered as sodium pregnanediol glucuronidate.The gravimetric method of Venning for the quantitative estimation of pregnanediol is long and tedious and it has the disadvantage that a number of factors other than progesterone influence the excretion of glucuronidate. Astwood and J ones'' described a method for the determination of free pregnanediol utilizing the hydrolysis of glucuronidate. Talbot et at. a made use of the color reaction produced by pure sulphuric acid to provide a colorimetric method for the quantitative determination of pregnanediol. Guterman" modified the Astwood-Jones method to provide for the more rapid qualitative determination of pregnanediol and made it more applicable to clinical use.The quantitative method described here has the advantage of simplicity thereby making it possible to follow patients over long periods of time by serial determinations permitting the study of the complications of pregnancy and the evaluation of their therapy. The determination of free pregnanediol rather than the conjugated sodium pregnanediol glucuronidate avoids the danger of loss incurred during the urine collection period. Furthermore, other substances than pregnanediol are found in the urine as glucuronidates interfering with the accuracy of the determinations.During the past year we have carried out over 1500 determinations of pregnanediol in the urine in about 100 patients. Some of these women had normal pregnancies and serial determinations were made throughout their pregnancies and for a week following their deliveries. These women served as normal controls to evaluate the method and to establish basic curves of pregnanediol excretion. The majority of the women had pregnancy complications in whom it was, desired to follow the pregnanediol excretion in order to determine any variations from the normal curves in an attempt to establish the role of progesterone metabolism in these complications. In many of these patients daily determinations were possible but in the majority the collections of urine were made 2 and 3 times a week. All of the determinations have been made in duplicate to decrease the likelihood of error in the method.Method. The women studied for the most part were out-patients who visited this clinic. They were given standard containers for urine collection and were carefully instructed to insure complete 24 hour samples. The first morning specimen on the day of collection was discarded and all urine throughout the day and at ...

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