Bayesian Pharmacokinetics of Gentamicin in a Haemodialysis Population

Abstract Background: Aminoglycosides are commonly used in the haemodialysis population. Standard pharmacokinetic approaches require multiple sampling to describe the parameters of drug distribution and elimination in the intra- and interdialytic periods. Objective: To characterise the pharmacokineti...
Ausführliche Beschreibung

Abstract Background: Aminoglycosides are commonly used in the haemodialysis population. Standard pharmacokinetic approaches require multiple sampling to describe the parameters of drug distribution and elimination in the intra- and interdialytic periods. Objective: To characterise the pharmacokinetics of gentamicin in a haemodialysis population by using Bayesian pharmacokinetic methods and only two plasma concentrations. Design and participants: Prospective case series of 13 adult (aged 36–70 years) haemodialysis patients (Fresenius F80 dialysers were used) receiving gentamicin. Methods: Patients with suspected or confirmed Gram-negative infections were given gentamicin. At 48 hours after receiving the dose (at the next haemodialysis session), patients provided two blood samples, one immediately before the dialysis session and another 1 hour after haemodialysis. Data on dosage, timing and plasma concentrations for all subjects were analysed with PASTRX version 10.6 and Bayesian pharmacokinetic analysis. Volume of distribution (Vd), interdialytic elimination rate constant ($ k_{inter} $), interdialytic elimination half-life (t½β, inter) and interdialytic clearance ($ CL_{inter} $) were determined from a single predialysis plasma concentration. Elimination rate constant (kdinal), elimination half-life (t½β, dial) and clearance ($ CL_{dial} $) during 3.5–4 hours of dialysis were also determined from the pre- and post-plasma concentrations. Results: Pharmacokinetic parameters (mean ± SD) were: Vd 0.288 ± 0.002 L/kg, kinter 0.015 ± 0.$ 004h^{−1} $, t½β, inter 48 ± 11h, CLinter 5.9 ± 2.4 mL/min, kdial 0.25 ±0.05 $ h^{−1} $, t½β, dial 3.0 ± 1.0h and $ CL_{dial 91 ± 24} $ mL/min. Conclusion: The rate of elimination of gentamicin was 17-fold greater (95% CI 13.7–20.7) on haemodialysis with a Fresenius F80 than off haemodialysis. All of the pharmacokinetic parameters of interest were determined using Bayesian pharmacokinetic procedures and only two plasma gentamicin concentrations. Ausführliche Beschreibung