TITLE

Oral bioavailability of linezolid before and after Roux-en-Y gastric bypass surgery: is dose modification necessary in obese subjects?

AUTHOR(S)
Hamilton, Rhonda; Thai, Xia C.; Ameri, Darius; Pai, Manjunath P.
PUB. DATE
March 2013
SOURCE
Journal of Antimicrobial Chemotherapy (JAC);Mar2013, Vol. 68 Issue 3, p666
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Objectives We characterized the pharmacokinetics of intravenous (iv) and oral linezolid before and after Roux-en-Y gastric bypass surgery (RYGBS). Methods 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. Results 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. Conclusions 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.
ACCESSION #
85442156

 

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