Pharmacokinetically determined cyclosporine dosage in young children

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Abstract
To account for the individual variability in cyclosporine pharmacokinetics and the non-existence of dosing recommendations in young children, we studied the pharmacokinetics of cyclosporine before renal transplantation in ten children aged 1.1–2.5 years, to determine the appropriate individual dose. Our aim was to reach a steady-state cyclosporine blood level of 200–300 μg/l, 8 h after a dose in the first days after renal transplantation. Cyclosporine was given as a single oral dose (10 mg/kg) or as a 4-h i. v. infusion (3 mg/kg), and the blood concentration was determined for 24 h by a specific monoclonal radioimmunoassay. The mean terminal cyclosporine half-life (t 1/2) was 9.3 h (range 2.8–20.4), blood clearance 10.8 ml/min per kilogram (range 6.8–22.7) and volume of distribution 2.8 l/kg (range 1.4–4.7). The bioavailability of oral cyclosporine was low; the mean amount absorbed was 21.8% of the administered dose (range 11–35). The mean calculated dose needed to attain the intended predose blood cyclosporine level of 200–300 μg/l at steady-state was 5 mg/kg per day for i.v. and 21 mg/kg per day for oral administration. In view of the shortt 1/2, we used three doses/day. The validity of the predicted doses is shown by the mean cyclosporine doses used during the first 10 days after transplantation, which were 93.5% of the calculated oral and 96.6% of the calculated i.v. doses. The observed mean cyclosporine concentration during the same period was 196 μg/l.