Population pharmacokinetics of vancomycin in obesity: Finding the optimal dose for (morbidly) obese individuals
Aims: For vancomycin treatment in obese patients, there is no consensus on the optimal dose that will lead to the pharmacodynamic target (area under the curve 400–700 mg h L−1). This prospective study quantifies vancomycin pharmacokinetics in morbidly obese and nonobese individuals, in order to guide vancomycin dosing in the obese. Methods: Morbidly obese individuals (n = 20) undergoing bariatric surgery and nonobese healthy volunteers (n = 8; total body weight [TBW] 60.0–234.6 kg) received a single vancomycin dose (obese: 12.5 mg kg−1, maximum 2500 mg; nonobese: 1000 mg) with plasma concentrations measured over 48 h (11–13 samples per individual). Modelling, internal validation, external validation using previously published data and simulations (n = 10.000 individuals, TBW 60–230 kg) were performed using NONMEM. Results: In a 3-compartment model, peripheral volume of distribution and clearance increased with TBW (both p < 0.001), which was confirmed in the external validation. A dose of 35 mg kg−1 day−1 (maximum 5500 mg/day) resulted in a > 90% target attainment (area under the curve > 400 mg h L−1) in individuals up to 200 kg, with corresponding trough concentrations of 5.7–14.6 mg L−1 (twice daily dosing). For continuous infusion, a loading dose of 1500 mg is required for steady state on day 1. Conclusion: In this prospective, rich sampling pharmacokinetic study, vancomycin clearance was well predicted using TBW. We recommend that in obese individuals without renal impairment, vancomycin should be dosed as 35 mg kg−1 day−1 (maximized at 5500 mg/day). When given over 2 daily doses, trough concentrations of 5.7–14.6 mg L−1 correspond to the target exposure in obese individuals.
|Keywords||glycopeptides, morbid obesity, obesity, pharmacokinetics, pharmacology, vancomycin|
|Persistent URL||dx.doi.org/10.1111/bcp.14144, hdl.handle.net/1765/124075|
|Journal||British Journal of Clinical Pharmacology|
Smit, C. (Cornelis), Wasmann, R.E. (Roeland E.), Goulooze, S.C. (Sebastiaan C.), Wiezer, M.J, van Dongen, E.H.P.A, Mouton, J.W, … Knibbe, C.A.J. (2019). Population pharmacokinetics of vancomycin in obesity: Finding the optimal dose for (morbidly) obese individuals. British Journal of Clinical Pharmacology. doi:10.1111/bcp.14144