Frederiksen M C, Ruo T I, Chow M J, Atkinson A J
Clin Pharmacol Ther. 1986 Sep;40(3):321-8. doi: 10.1038/clpt.1986.183.
Theophylline pharmacokinetics were studied serially in five women during and after pregnancy. Theophylline protein binding was reduced to 11.1% +/- 4.7% (P less than 0.01) and 13.0% +/- 5.9% (P less than 0.01) during the second and third trimesters of pregnancy, respectively, compared with 28.1% +/- 2.8% when the patients were more than 6 months postpartum. Similar comparisons indicate that theophylline distribution volume and elimination t1/2 were increased from 30.7 +/- 4.4 L and 262 +/- 57 minutes to 36.8 +/- 4.2 L (P less than 0.05) and 389 +/- 73 minutes (P less than 0.01) in the third trimester of pregnancy. In the second and third trimesters, intrinsic nonrenal clearance was reduced to 0.82 +/- 0.25 ml/min X kg (P less than 0.05) and 0.67 +/- 0.18 ml/min X kg (P less than 0.01) compared with a remote postpartum value of 1.25 +/- 0.37 ml/min X kg. However, these reductions were offset by increases in theophylline intrinsic renal clearance so that apparent reductions in the overall unbound clearance of this drug did not reach statistical significance either during pregnancy or in the early postpartum period.
对五名女性在孕期及产后进行了茶碱药代动力学的系列研究。与产后6个月以上时28.1%±2.8%的茶碱蛋白结合率相比，孕期第二和第三阶段的茶碱蛋白结合率分别降至11.1%±4.7%（P<0.01）和13.0%±5.9%（P<0.01）。类似的比较表明，孕期第三阶段茶碱的分布容积和消除半衰期从30.7±4.4L和262±57分钟增加至36.8±4.2L（P<0.05）和389±73分钟（P<0.01）。在孕期第二和第三阶段，与产后远期1.25±0.37ml/min·kg的值相比，非肾内清除率分别降至0.82±0.25ml/min·kg（P<0.05）和0.67±0.18ml/min·kg（P<0.01）。然而，这些降低被茶碱肾内清除率的增加所抵消，因此该药物总体非结合清除率在孕期或产后早期的明显降低均未达到统计学意义。
