Characterization of theophylline binding to serum proteins in pregnant and nonpregnant women.

Sera from 10 subjects in the third trimester of pregnancy and from 10 nonpregnant women were studied to elucidate the mechanism underlying decreased theophylline protein binding during pregnancy. Consistent with the physiologic hypoalbuminemia of pregnancy, serum albumin concentrations averaged only 3.2 +/- 0.3 gm/dl (+/- SD) in pregnant subjects, compared with 4.4 +/- 0.3 gm/dl in control subjects (p less than 1 x 10(-6], and this was the main cause of decreased theophylline binding. Saturation binding studies indicated a single class of theophylline binding sites. Theophylline binding capacity (N) was greater in pregnant (N = 4.3 +/- 1.0) than in nonpregnant (N = 3.3 +/- 0.4) subjects, but binding affinity (ka) averaged only 227 +/- 69 (mol/L)-1 in pregnant subjects, compared with 303 +/- 44 (mol/L)-1 in control subjects (F2,17 = 4.26; p = 0.032). At a theophylline plasma concentration of 10 micrograms/ml, the combined effects of hypoalbuminemia and lowered ka would reduce theophylline binding to 31% +/- 3% in pregnant women, compared to 39% +/- 3% in nonpregnant control subjects (p less than 1 x 10(-5]. Nonesterified fatty acid concentrations were similar in both subject groups and did not contribute to the pregnancy-associated decrease in theophylline binding.