Influence of Morbid Obesity on the Clinical Pharmacokinetics of Various Anti-Infective Drugs: Reappraisal Using Recent Case StudiesIssues, Dosing Implications, and Considerations

摘要

Owing to availability of scanty pharmacokinetic data, dosing decisions in morbid obesity is increasingly challenging in the field of anti-infective drugs. However, in recent years data are emerging that describe the pharmacokinetics of anti-infective drugs in morbidly obese subjects. The objectives of the present work were: (1) to collate the recent reports pertaining to the pharmacokinetics in morbidly obese subjects for several anti-infective drugs and provide an overview of the pharmacokinetic data along with the applicable pharmacodynamics and/or clinical outcome; (2) to perform regression analysis on limited dataset for a few drugs to verify the existence of relationships between C-max/C-trough versus steady-state volume of distribution (Vss)/clearance to enable data prediction in morbid obesity subjects; (3) to provide a general discussion on issues and dosing implications. The key findings of this review were: (a) drugs such as vancomycin, ethambutol, and fluconazole, where the V-SS is substantially greater in morbidly obese patients, need a dosing strategy with the appropriate body mass descriptors; (b) other drugs such as moxifloxacin, linezolid, doripenem, meropenem, voriconazole, oseltamivir, tigecycline, levofloxacin may not ordinarily need dosing adjustments; (c) using regression analysis of limited data, it seemed that drugs such as vancomycin, voriconazole, oseltamivir, and oseltamivir carboxylate may be amenable for the prediction of V-SS and/or clearance in morbid obesity patients.