DDMODEL00000317: PK_Vancomycin_Obese

  public model
Short description:
PK model of vancomycin in non-obese and obese individuals with normal renal function
Original code
  • Population pharmacokinetics of vancomycin in obesity: Finding the optimal dose for (morbidly) obese individuals.
  • Wasmann RE, Wiezer MJ, van Dongen EPA, Mouton JW, Brüggemann RJM
  • British journal of clinical pharmacology, 10/2019
  • Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands.
  • 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.
Cornelis Smit
Context of model development: Patient Population Selection and Bridging between Population (Pediatrics, Elderly, Obese);
Long technical model description: A 3-compartment model a combined error model. M3 method was used for data below LOD. Body weight found as covariate on CL, WT and AGE on V1/V2. Seperate ETA's for LC in non-obese and obese individuals were described..;
Model compliance with original publication: Yes;
Model implementation requiring submitter’s additional knowledge: No;
Modelling context description: Dose finding in the obese population;
Modelling task in scope: simulation;
Nature of research: Clinical research & Therapeutic use;
Therapeutic/disease area: Anti-infectives;
Annotations are correct.
This model is not certified.
  • Model owner: Cornelis Smit
  • Submitted: Jan 31, 2020 5:45:42 PM
  • Last Modified: Jan 31, 2020 5:45:42 PM
  • Version: 5 public model Download this version
    • Submitted on: Jan 31, 2020 5:45:42 PM
    • Submitted by: Cornelis Smit
    • With comment: Updated model annotations.