The pharmacokinetics of ketobemidone in critically ill patients

Aims To study the pharmacokinetics of orally and intravenously administered ketobemidone in critically ill patients. Methods Seventeen patients were studied during their stay in the intensive care unit at Huddinge University Hospital. Nine patients received a single intravenous dose of ketobemidone (0.04 mg kg(-1) ) and eight patients received a single oral dose of 5 mg. Plasma concentrations of ketobemidone were measured using liquid chromatography-mass spectrometry. The pharmacokinetic analysis was performed using WinNonlin(TM) software. Results There was a wide variation in the different pharmacokinetic parameters among patients. Mean clearance in patients treated intravenously was 74.5 (95% CI 43.2, 128.3) and mean V (d) was 2.4 l kg(-1) (95% CI 2.0, 2.8). t (1/2,z) also varied widely with a mean value of 4.41 h (95% CI 2.7, 7.0). The corresponding values for MRT were 5.4 and 3.3, 8.8. Mean oral clearance (CL/F ) was 102 l h(-1) (95% CI 82.7, 125.8), mean V (z) /F was 11.2 l kg(-1) (95% CI 9.7, 13.1) and mean t (1/2,z) was 6.0 (95% CI 4.9, 7.3) in orally treated patients. C (max) showed a mean of 38 nmol l(-1) (95% CI of 31, 47). A significant correlation was observed between the glomerular filtration rate (GFR) and the half-life of ketobemidone (r = -0.72, P < 0.05). t (1/2,z) was generally longer and the variation larger in critically ill patients compared with healthy individuals. However, there was no correlation between the elimination of ketobemidone in critically ill patients and plasma C-reactive protein, white blood count or plasma albumin concentrations. Conclusions The disposition of ketobemidone is highly variable in critically ill patients. In order to ensure sufficient analgesia and avoid toxicity, therapeutic monitoring should be employed when using ketobemidone in this group of patients.