Pharmacokinetics after an intravenous single dose of the opioid ketobemidone in children

Background: Ketobemidone is often used as an alternative to morphine in children in the Scandinavian countries. The aim of this clinical trial was to explore the pharmacokinetics of ketobemidone in children because these properties have not been reported previously. Methods: Thirty children, newborn to 10 years, scheduled for elective surgery were included in the trial. Ketobemidone hydrochloride was administered as a single intravenous bolus dose and ketobemidone and norketobemidone concentrations were measured by LC-MS over 8 h. Pharmacokinetic parameters were determined using compartmental methods. Results: Six children were excluded from pharmacokinetic analysis because of incomplete blood sampling. The values of ketobemidone clearance (l/h/kg) given as median (range) were 0.84 (0.29–3.0) in Group A (0–90 days), 0.89 (0.55–1.35) in Group B (1–2.5 years) and 0.74 (0.50–0.99) in Group C (7–10 years). The corresponding values for apparent volume of distribution (l/kg) were 4.4 (3.7–6.9) (Group A), 2.6 (2.0–5.6) (Group B) and 3.9 (2.7–5.0 (Group C), and for elimination half-life (h) 3.0 (1.4–8.9) (Group A), 2.0 (1.2–4.7) (Group B) and 3.7 (2.4–6.9) (Group C), respectively. In the two neonates the elimination half-life was almost 9 h. The metabolite norketobemidone did not reach levels above the limit of quantification (0.07 ng/ml) in any of the patients. Conclusion: The pharmacokinetic parameters of ketobemidone in children older than 1 month appear to be similar to those in adults. Because of the large interindividual variability of the pharmacokinetics in neonates, further studies especially in this age group are warranted.