ABSTRACTThe pharmacokinetics of linezolid was assessed in 20 adult volunteers with body mass indices (BMI) of 30 to 54.9 kg/m2receiving 5 intravenous doses of 600 mg every 12 h. Pharmacokinetic analyses were conducted using compartmental and noncompartmental methods. The mean (±standard deviation) age, height, and weight were 42.2 ± 12.2 years, 64.8 ± 3.5 in, and 109.5 ± 18.2 kg (range, 78.2 to 143.1 kg), respectively. Linezolid pharmacokinetics in this population were best described by a 2-compartment model with nonlinear clearance (original value, 7.6 ± 1.9 liters/h), which could be inhibited to 85.5% ± 12.2% of its original value depending on the concentration in an empirical inhibition compartment, the volume of the central compartment (24.4 ± 9.6 liters), and the intercompartment transfer constants (K12andK21) of 8.04 ± 6.22 and 7.99 ± 5.46 h−1, respectively. The areas under the curve for the 12-h dosing interval (AUCτ) were similar between moderately obese and morbidly obese groups: 130.3 ± 60.1 versus 109.2 ± 25.5 μg · h/ml (P= 0.32), and there was no significant relationship between the AUC or clearance and any body size descriptors. A significant positive relationship was observed for the total volume of distribution with total body weight (r2= 0.524), adjusted body weight (r2= 0.587), lean body weight (r2= 0.495), and ideal body weight (r2= 0.398), but not with BMI (r2= 0.171). Linezolid exposure in these obese participants was similar overall to that of nonobese patients, implying that dosage adjustments based on BMI alone are not required, and standard doses for patients with body weights up to approximately 150 kg should provide AUCτ values similar to those seen in nonobese participants.
Reversal of a continuous deep neuromuscular blockade with sugammadex in morbidly obese patients: lean body weight or total body weight as dosing scalar?