[Pharmacokinetics of drugs from the breast-feeding mother passing into the body of the infant, using theophylline as an example].

In order to find out whether theophylline medication during the lactation period would produce hazards in the suckling infant or not, the following investigations were performed: 1. After oral application of theophylline to 12 nursing mothers the pharmacokinetics of the translactal passage was determined by simultaneous measurements in serum and milk. 2. For predicting the drug uptake by the suckling infant a pharmacokinetic model was designed allowing estimations of drug uptake by the infant on the basis of the kinetics of the translactal passage and the kinetics of the drug in the infant. The following results were obtained: 1. Theophylline passes the blood milk barrier with a certain delay. The time courses of theophylline in the milk thus were depressed when compared to those in the serum. The milk/plasma-quotient varied within a range of 0.6 to 0.89 and was less when maxima of theophylline in plasma were reached. Elimination half-lifes did not differ, but the apparent volume of distribution was greater in milk. This difference showed a good correlation to the divergent areas under the curves for milks and serum concentrations. 2. The kinetic data of the translactal passage of theophylline and the kinetic data of theophylline in infants were fitted into the kinetic model presuming constant dosage intervals as well as constant amounts and intervals of drinking. Theophylline accumulation occurred highly dependent upon the half-life in the infant. This accumulation reached therapeutic levels and even could surpass these when long half-lifes were assumed. For the estimation of drug transfer from breast feeding mothers to their infants via breastmilk, several pharmacokinetic criteria should be considered.