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Biomedical subjects

M Dean

Publications and source records attributed to M Dean.

At least 397 records · Page 22Linked to original sources
PubMed1980

Serum protein binding of drugs during and after pregnancy in humans.

The serum protein binding of three weakly acidic drugs (salicylic acid, sulfisoxazole, and phenytoin), one week base (diazepam), and one steroid (dexamethasone) was determined in pregnant women at seven time periods during pregnancy and at two periods post partum, as well as in a group of nonpregnant women of childbearing age. The serum free fraction values (ratio of concentrations, free to total drug) of all drugs rose during pregnancy, primarily after 15 wk of gestation, and remained elevated for at least 1 to 5 days post partum. Pregnancy had the greatest effect on protein binding of sulfisoxazole, diazepam, and salicylic acid. The magnitude of this effect is such that quantitatively significant changes in the pharmacokinetic and pharmacodynamic characteristics of certain drugs may be expected to occur during pregnancy (in addition to possible changes caused by other pregnancy-related effects such as altered activity of drug-metabolizing enzyme systems). All drugs but dexamethasone exhibited significant negative correlations between free fraction values and serum albumin concentrations during pregnancy. The serum protein binding of salicylic acid, but not the other drugs tested, was more extensive in nonpregnant women who were not taking oral contraceptives than in those who were.

Adolescent↗
PubMed1980

Serum protein binding of drugs during and after pregnancy in rats.

The serum protein binding of salicylic acid (SA), sulfisoxazole (SUL), phenytoin (P), dexamethasone (D), diazepam (DI) and bilirubin (B) was determined in Long-Evans rats during pregnancy and after parturition. Serum free fraction (f) values were obtained by equilibrium dialysis (drugs) and by a reaction rate method (B). Concurrent control experiments were carried out on nonpregnant animals. Values of f were not significantly different from controls during the first 10 to 15 days of pregnancy. Pronounced increases in f of SA, SUL, P and D were observed on the 20th and 21st day of pregnancy; the f of DI was increased only on the 21st day and the f of B was not significantly changed at any time. The f values for SA, SUL and P returned almost to control levels 2 days after parturition (D, DI and B were not studied at that time). Additional studies with SUL, P and D on the 20th day of pregnancy showed that the increase in f occurred over a wide concentration range. Total serum protein and albumin concentrations were significantly decreased only on the 21st day of pregnancy. Pretreatment with activated charcoal decreased f of SA, SUL, P and D (the other compounds were not studied) in serum of 20-day pregnant (but not control) animals. The decreased protein binding of drugs in serum of pregnant rats appears to be due, at least in part, to accumulation of endogenous displacing agents.

Animals↗