The Pharmacokinetics of Captopril in Infants with Congestive Heart Failure

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Abstract
Summary: The use of the angiotensin-converting enzyme inhibitor captopril in infants with congestive heart failure (CHF) has been empirical owing to a lack of relevant pharmacokinetic data. To determine standard pharmacokinetic parameters for the drug in this population, we administered captopril, 1 mg/kg, orally to 10 infants aged 6.8 ± 4.6 months. Sequential plasma unchanged and total (sum of unchanged and dimerized) captopril concentrations were determined using a high-performance liquid chromatographic method. Arterial pressure, systemic and pulmonary resistance, heart rate, and respiratory rate were all significantly decreased 1 h after the first dose of captopril. Plasma renin activity was not significantly increased. For unchanged captopril, the maximum concentration (Cmax) was 350 ± 184 ng/ml; the time to Cmax (Tmax), 1.6 ± 0.4 h; elimination half-life (t1/2), 3.3 ± 3.3 h; oral clearance (Clo), 1.1 ± 0.4 L/h/kg. For total captopril, Cmax was 1,088 ± 621 ng/ml; Tmax, 2.7 ± 1.1 h; t1/2, 3.4 ± 1.0 h. Thus, we conclude that the pharmacokinetic parameters for captopril in infants with CHF are within the range reported for adults with CHF. Also, the hemodynamic changes, measured 1 h after the first dose, indicate that the acute effects of captopril in infants with CHF are beneficial.

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