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Terbutaline in breast milk.

Nursing mothers with chronic bronchial asthma or obstructive lung disease may require treatment with bronchodilating drugs and the question then arises whether or not these drugs are present in breast milk in concentrations that entail risk for adverse effects in the infants. Theophylline kinetics in breast milk have been studied (Yurchak & Jusko, 1976; Stec et al., 1980), and it was concluded that the risk for toxic effects in the baby was low. To our knowledge, no information is available about the appearance in milk of f32-adrenoceptor agonists, such as fenoterol, salbutamol, or terbutaline. A sensitive massspectrometric technique for the determination of terbutaline in plasma has recently been presented (Jacobsson et al., 1980), and the pharmacokinetics of the drug can therefore now be clarified in more detail. This method has been utilized in the present study, which reports the terbutaline concentrations in breast milk and plasma from nursing mothers who were on continuous treatment with terbutaline because of obstructive lung disease. The two mothers (H.B. 27 years, 66 kg body weight and A.W. 30 years, 75 kg body weight) were treated with a dose of 2.5 mg terbutaline sulphate three times a day. No other drugs were given. Both mothers were in good general condition with their asthma well controlled. The infants, approximately 3 weeks of age, were healthy and had a normal development. The investigation was performed after at least 2 weeks' treatment of the mothers with terbutaline. Nursing had proceeded normally. Blood from an antecubital vein and milk were sampled from the mothers during a period of up to 8 h after the morning dose of terbutaline. No milk was taken from the left breast until 4 h after tablet intake. Milk was collected with a pump at the early phase of the meal. For comparison, on one occasion in each mother, milk from the late phase of the meal was also sampled. Plasma and milk samples were frozen and later analysed for terbutaline. In the last sample from each mother, also the concentration of terbutaline in skimmed milk was determined. After nursing any remaining milk in the breasts was removed with the pump. The results are shown in Table 1. Despite the same dose, patient H.B. reached only about half the terbutaline concentration of patient A.W. Milk samples from the left and right breast showed similar concentrations, except for the last sampling in patient A.W. Thus, delaying the sampling from the left breast did not influence the concentration of terbutaline in the milk. The terbutaline concentrations in milk were always higher than in plasma. This is in agreement with the principle of non-ionic diffusion, which predicts a higher concentration in milk of substances that are more ionized at the pH of human milk