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

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/m(2) received a single iv 600 mg dose of linezolid followed by the same oral dose after a 7 day washout period betw...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2013-03, Vol.68 (3), p.666-673
Main Authors: Hamilton, Rhonda, Thai, Xia C, Ameri, Darius, Pai, Manjunath P
Format: Article
Language:English
Subjects:
Acetamides - administration & dosage
Acetamides - pharmacokinetics
Administration, Oral
Age
Anti-Bacterial Agents - administration & dosage
Anti-Bacterial Agents - pharmacokinetics
Antibiotics
Bioavailability
Biological Availability
Body mass index
Chromatography, High Pressure Liquid
Drug dosages
Female
Gastric Bypass
Gastrointestinal surgery
High-performance liquid chromatography
Humans
Intravenous administration
Linezolid
Male
Middle Aged
Obesity
Oxazolidinones - administration & dosage
Oxazolidinones - pharmacokinetics
Pharmacodynamics
Pharmacokinetics
Pharmacology
Serum - chemistry
Spectrophotometry, Ultraviolet
Surgery
U.V. radiation
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Summary: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/m(2) 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 (AUC(0-∞)) 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/m(2). 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) AUC(0-∞) 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
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dks431