This prospective study quantifies vancomycin pharmacokinetics in morbidly obese and non-obese individuals, in order to guide vancomycin dosing in the obese” Smit et al (2019).
AIMS: For vancomycin treatment in obese patients, there is no consensus on the optimal dose that will lead to the pharmacodynamic target (AUC 400-700 mg*h L-1 ). This prospective study quantifies vancomycin pharmacokinetics in morbidly obese and non-obese individuals, in order to guide vancomycin dosing in the obese.
METHODS: Morbidly obese individuals (n=20) undergoing bariatric surgery and non-obese 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; non-obese: 1000 mg) with plasma concentrations measured over 48 hours (11-13 samples per individual). Modelling, internal validation, external validation using previously published data and simulations (n=9950 individuals, TBW 60-230 kg) were performed using NONMEM.
RESULTS: In a three-compartment model, peripheral volume and clearance increased with TBW (both p<0.001), which was confirmed in the external validation. A dose of 35 mg kg-1 per day (maximum 5500 mg/day) resulted in a >90% target attainment (AUC>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.
CONCLUSIONS: 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 per day (maximized at 5500 mg/day). When given over two daily doses, trough concentrations between 5.7-14.6 mg L-1 correspond to the target exposure in obese individuals.
You may also be interested in…
Smit, C., Wasmann, R.E., Goulooze, S.C., Wiezer, M.J., van Dongen, E.P.A., Mouton, J.W., Brüggemann, R.J.M. and Knibbe, C.A.J. (2019) Population pharmacokinetics of vancomycin in obesity: finding the optimal dose for (morbidly) obese individuals. British Journal of Clinical Pharmacology. October 29th. doi: 10.1111/bcp.14144. .