DDMODEL00000316: PK_Tobramycin_Obese

  public model
Short description:
PK model for Tobramycin developed in both non-obese and obese individuals with normal renal function
Original code
  • Tobramycin Clearance Is Best Described by Renal Function Estimates in Obese and Non-obese Individuals: Results of a Prospective Rich Sampling Pharmacokinetic Study.
  • Smit C, Wasmann RE, Wiezer MJ, van Dongen HPA, Mouton JW, Brüggemann RJM, Knibbe CAJ
  • Pharmaceutical research, 5/2019, Volume 36, Issue 8, pages: 112
  • Department of Clinical Pharmacy, St. Antonius Hospital, Koekoekslaan 1, 3435, CM, Nieuwegein, The Netherlands.
  • PURPOSE:Tobramycin is an aminoglycoside antibiotic of which the 24 h exposure correlates with efficacy. Recently, we found that clearance of the aminoglycoside gentamicin correlates with total body weight (TBW). In this study, we investigate the full pharmacokinetic profile of tobramycin in obese and non-obese individuals with normal renal function. METHODS:Morbidly obese individuals (n?=?20) undergoing bariatric surgery and non-obese healthy volunteers (n?=?8), with TBW ranging 57-194 kg, received an IV dose of tobramycin with plasma concentrations measured over 24 h (n?=?10 per individual). Statistical analysis, modelling and simulations were performed using NONMEM. RESULTS:In a two-compartment model, TBW was the best predictor for central volume of distribution (p?
Cornelis Smit
Context of model development: Patient Population Selection and Bridging between Population (Pediatrics, Elderly, Obese);
Long technical model description: A 2-compartment model with combined error model and M3 method for BLQ data with de-indexed MDRD (corrected for BSA) as covariate on CL and WT as covariate on V1;
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 5:34:50 PM
  • Last Modified: Jan 31, 2020 5:34:50 PM
  • Version: 12 public model Download this version
    • Submitted on: Jan 31, 2020 5:34:50 PM
    • Submitted by: Cornelis Smit
    • With comment: Edited model metadata online.