Effect of late pregnancy on salicylate, diazepam, warfarin, and propranolol binding: Use of fluorescent probes

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Abstract
Serum protein binding was measured in 6 women 38 wk pregnant and in 5 control subjects. Three distinct binding sites for drugs on human serum albumin were identified. To determine whether changes in binding during pregnancy occur for common drugs or only for drugs that bind to a specific binding site, serum protein binding of 3 drugs (diazepam (site I), warfarin (site III) and salicylate) and 4 fluorescent probes (dansylsarcosine (site I), 1-anilino-8-naphthalenesulfonate (site I), 7-anilinocoumarin-4-acetic acid (site II) and 5-dimethylaminonaphthalene-1-sulfonamide (DNSA) (site III) were determined in control and pregnant sera. Unbound fractions of diazepam and salicylate in pregnant women increased but the unbound fraction of warfarin did not change. Kd of all fluorescent probes but DNA were almost the same in control and pregnant sera, while the Kd of DNSA in pregnant serum was approximately 50% of control. Binding capacities of all probes decreased, which was attributed to decreased serum albumin concentration. Evidently, serum protein binding of drugs that bind to site I or site II on albumin decreased largely because of the reduced serum albumin concentration during pregnancy, and the binding of drugs that bind to site III changed little because of compensating effects of the decrease in serum albumin concentration and the increase in binding affinity to serum albumin. Serum concentration of .alpha.1-acid glycoprotein and serum binding of propranolol did not change in pregnant women.