Читать книгу Clinical Pharmacology and Therapeutics - Группа авторов - Страница 99

Maternal plasma volume and extracellular fluid volume increase by about 50% by the last trimester, and this may decrease the steady‐state concentration of drugs with a small volume of distribution. Considerable changes in protein concentration occur during the last trimester, with serum albumin falling by about 20% while α₁‐acid glycoprotein increases in concentration by about 40% in normal pregnancies. These changes are accentuated in pre‐eclampsia, with albumin concentration falling by about 35% and glycoprotein rising by as much as 100%. This means that the free fraction of acidic drugs can increase substantially, while that of basic drugs can be decreased greatly, in the last trimester. Diazepam, phenytoin and sodium valproate have been shown to have significantly elevated free fractions in the last trimester.