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/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. 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/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<0.001). This increase in AUC(0-∞) 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.
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/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. 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/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<0.001). This increase in AUC(0-∞) 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.
Authors: Marina Becker Sales Rocha; Gilberto De Nucci; Francisco Ney Lemos; Rodrigo Feitosa de Albuquerque Lima Babadopulos; Andrea Vieira Pontes Rohleder; Francisco Vagnaldo Fechine; Natalícia J Antunes; Gustavo D Mendes; Demetrius Fernandes do Nascimento; Manoel Odorico de Moraes; Maria Elisabete Amaral de Moraes Journal: Obes Surg Date: 2019-03 Impact factor: 4.129
Authors: Matthieu Grégoire; Julia Brochard Libois; Denis Waast; Benjamin Gaborit; Marc Dauty; Guillaume Deslandes; Eric Dailly; Sophie Touchais; David Boutoille; Nicolas Grégoire; William Couet Journal: Antimicrob Agents Chemother Date: 2018-03-27 Impact factor: 5.191
Authors: Lieke Mitrov-Winkelmolen; Marie-Christine W van Buul-Gast; Dingeman J Swank; Hans W P M Overdiek; Ron H N van Schaik; Daan J Touw Journal: Obes Surg Date: 2016-09 Impact factor: 4.129