Longitudinal effects of pregnancy on the pharmacokinetics of theophylline

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.