[Pharmacokinetic examination of theophylline in pregnancy in cases of fetal anoxia].

The purpose of the investigation was to determine the effects of pregnancy on theophylline pharmacokinetics and to clarify the clinical effect of theophylline treatment in cases of threatened anoxemia of foetus. The study was carried out in 15 pregnant women between 28 and 32 weeks of pregnancy with chronic anoxemia of the foetus. The women obtained Aminophyllinum "Polfa" 250 mg (201.3 mg of theophylline) every 12 hours for 4 days to achieve the steady-state of theophylline. After the first dose the drug concentration reached the level of theophylline in range of 12.05 +/- 4.57 micrograms/ml in 15 minutes to 3.62 +/- 0.74 micrograms/ml in 12 hours. The subsequent doses increased the concentration and in steady-state the concentration fluctuates between 21.48 +/- 10.00 micrograms/ml and 6.20 +/- 1.56 micrograms/ml, what coincides with established therapeutic range of theophylline (10-20 micrograms/ml). Elimination of the drug was characterised by calculation of the elimination rate constant and drug-clearance. Both parameters are higher after a single administration what suggest the accumulation of theophylline after multiple drug administration by the saturation of enzymes taking part in metabolism of the drug. Attention should be paid higher values of half-life in pregnancy in comparison with those obtained previously in healthy volunteers. Comparative investigations of the level of theophylline in amniotic fluid in relation to maternal blood in steady-state showed a high correlation between these two values (r = 0.7867, p < 0.006). The proportion of the concentration of theophylline in relation to that in maternal blood is about 60% (0.5978 +/- 0.1599).(ABSTRACT TRUNCATED AT 250 WORDS)