Oral bioavailability of linezolid before and after Roux-en-Y gastric bypass surgery: is dose modification necessary in obese subjects?
Open Access
- 15 November 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Antimicrobial Chemotherapy
- Vol. 68 (3), 666-673
- https://doi.org/10.1093/jac/dks431
Abstract
We characterized the pharmacokinetics of intravenous (iv) and oral linezolid before and after Roux-en-Y gastric bypass surgery (RYGBS). Subjects with a body mass index (BMI) > 35 kg/m2 received a single iv 600 mg dose of linezolid followed by the same oral dose after a 7 day washout period between doses, before and 3 months after RYGBS. Serum linezolid concentrations were measured by a validated HPLC method with ultraviolet detection. Parametric population pharmacokinetic analysis was used to evaluate bioavailability and the influence of total body weight (TBW) on pharmacokinetic parameters. The area under the serum concentration–time curve extrapolated to infinity (AUC0–∞) was compared between subjects before and after RYGBS, and with non-obese controls. Five (four male) obese subjects were studied with a mean (SD) age of 51.4 (5.01) years, TBW of 124 (10.6) kg and initial BMI of 44.9 (7.52) kg/m2. The bioavailability was a mean (95% CI) of 1.14 (0.816–1.47) before and 1.14 (1.01–1.26) after RYGBS. The mean (SD) AUC0–∞ with oral linezolid before RYGBS was 41.6 (20.9) mg·h/L compared with 98.9 (24.7) mg·h/L after RYGBS (P < 0.001). This increase in AUC0–∞ corresponded with a 25.3% reduction in the TBW after RYGBS, as the TBW was a significant covariate of clearance. The probability of pharmacodynamic target attainment with standard doses of linezolid is lower in obese versus non-obese individuals. The bioavailability of linezolid is not impaired by RYGBS. The serum exposure of linezolid is more than 50% lower in obese compared with non-obese subjects, suggesting that dose modification may be needed.Keywords
This publication has 20 references indexed in Scilit:
- Effect of Gastric Bypass Surgery on the Absorption and Bioavailability of MetforminDiabetes Care, 2011
- A systematic review of drug absorption following bariatric surgery and its theoretical implicationsObesity Reviews, 2009
- Pharmacokinetics of mycophenolic acid, tacrolimus and sirolimus after gastric bypass surgery in end‐stage renal disease and transplant patients: a pilot studyClinical Transplantation, 2007
- Does Linezolid Inhibit Its Own Metabolism?—Population Pharmacokinetics As a Tool to Explain the Observed Nonlinearity in Both Healthy Volunteers and Septic PatientsDrug Metabolism and Disposition, 2007
- Malabsorption of Oral Antibiotics in Pregnancy after Gastric Bypass SurgeryThe Journal of the American Board of Family Medicine, 2007
- Pharmacokinetic/Pharmacodynamic Factors Influencing Emergence of Resistance to Linezolid in an In Vitro ModelAntimicrobial Agents and Chemotherapy, 2007
- Standardization of pharmacokinetic/pharmacodynamic (PK/PD) terminology for anti-infective drugs: an updateJournal of Antimicrobial Chemotherapy, 2005
- Quantification of Lean BodyweightClinical Pharmacokinetics, 2005
- Population Pharmacokinetics of Linezolid in Patients Treated in a Compassionate-Use ProgramAntimicrobial Agents and Chemotherapy, 2003
- A Bayesian extension of the minimum AIC procedure of autoregressive model fittingBiometrika, 1979