Gardner M J, Schatz M, Cousins L, Zeiger R, Middleton E, Jusko W J
Eur J Clin Pharmacol. 1987;32(3):289-95. doi: 10.1007/BF00607577.
The effects of pregnancy on the disposition of theophylline were assessed in 10 patients throughout pregnancy and post-partum. The clearance relative to total theophylline concentrations was only slightly affected during the first two trimesters (2.61 +/- 0.63 l/h and 2.85 +/- 1.05 l/h), while a statistically significant reduction was evident late in pregnancy (2.05 +/- 0.49 l/h). Post-partum clearance values (2.16 +/- 2.81 l/h) suggest an ongoing suppression relative to pre-pregnancy levels. A similar pattern was evident with clearance values based on free theophylline plasma concentrations (p = 0.12). Absolute volume of distribution increased in concert with gestation, suggesting that theophylline partitions into the enlarged tissue spaces. In addition, theophylline binding to plasma proteins decreased, albeit insignificantly, during the second (fraction bound = 29%) and third (32%) trimesters compared to post-partum values (41%). Increases in half-life during the third trimester (13.00 +/- 2.31 h vs 9.53 +/- 3.53 h post-partum) were highly significant. This change reflects the net effect of reduced clearance and increased distribution. Breast feeding had no effect on the disposition of theophylline, although the transfer of this compound into breast milk was confirmed.
在10名患者的整个孕期及产后评估了妊娠对茶碱处置的影响。相对于总茶碱浓度的清除率在前两个孕期仅受到轻微影响（分别为2.61±0.63升/小时和2.85±1.05升/小时），而在妊娠后期清除率出现了统计学上的显著降低（2.05±0.49升/小时）。产后清除率值（2.16±2.81升/小时）表明相对于孕前水平持续受到抑制。基于游离茶碱血浆浓度的清除率值也呈现出类似模式（p = 0.12）。分布容积绝对值随孕周增加，提示茶碱分布到扩大的组织间隙中。此外，与产后值（41%）相比，在孕中期（结合分数 = 29%）和孕晚期（32%）茶碱与血浆蛋白的结合减少，尽管不显著。孕晚期半衰期增加（13.00±2.31小时 vs 产后9.53±3.53小时）非常显著。这种变化反映了清除率降低和分布增加的综合影响。母乳喂养对茶碱的处置没有影响，不过证实了该化合物可转移至母乳中。
