Theophylline elimination in the pregnant and fetal rabbit

Aminophylline and theophylline are commonly used to treat asthma. We studied theophylline pharmacokinetics in the pregnant and nonpregnant rabbit as well as in the intrauterine and extrauterine fetus. The t1/2 was increased (p less than 0.05) and the clearance was decreased (p less than 0.05) in the pregnant compared to the nonpregnant rabbit. The t1/2 of theophylline in the newborn rabbit was 43.5 +/- 12.0 hr, approximately 15 times longer than in the nonpregnant rabbit. Twenty-four hours after a 20 min maternal aminophylline infusion, both the intrauterine fetus and maternal serum theophylline concentrations were very similar. The transplacental transfer from the maternal to fetal circulation occurred in less than 1 hr. The maternal to fetal serum ratios for theophylline were similar after a 5-day maternal aminophylline infusion (ratio 1.22 +/- 0.20) or after a 20 min infusion (ratio 1.24 +/- 0.20). Our findings indicate that the newborn rabbit eliminates theophylline very slowly, and maternal aminophylline or theophylline therapy that would result in high peak serum concentrations in the fetus, particularly just before birth, should be avoided.