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

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.

Bell's palsy associated with linezolid therapy: case report and review of neuropathic adverse events.

Bell's palsy is one of the most common neurologic disorders affecting the seventh cranial nerve. Several disease states have been associated with facial paralysis. Drugs, however, have been rarely implicated as an etiology. We describe a 49-year-old man who developed peripheral facial paralysis after 3 weeks of linezolid therapy, along with recurrence of symptoms on rechallenge. He had insulin-dependent diabetes mellitus and a longstanding history of bilateral diabetes-related foot problems. After hospitalization, debridement, and vancomycin therapy for methicillin-resistant Staphylococcus aureus osteomyelitis, the patient was discharged to home with oral linezolid therapy. On day 23 of linezolid therapy, he developed signs and symptoms that were consistent with Bell's palsy. Linezolid was discontinued; the Bell's palsy gradually improved, with complete resolution occurring at month 3. On rechallenge with linezolid for recurrent osteomyelitis, the patient developed a second episode of Bell's palsy within a similar time frame as in the first episode. Assessment of causality using the Naranjo adverse drug reaction probability scale revealed a probable relationship between this adverse drug event and linezolid therapy. Clinicians should be aware that Bell's palsy may be another neuropathic adverse effect associated with linezolid.