Plasma pharmacokinetics and tissue penetration of alatrofloxacin in morbidly obese individuals

Objectives: To characterise the peritoneal and subcutaneous adipose penetration of alatrofloxacin. If the extent of penetration of this lipophilic fluoroquinolone is adequate in patients with extensive adipose layers, it may provide better antimicrobial coverage than more commonly used antibiotics that are less lipophilic. Study Participants and Methods: Six morbidly obese individuals undergoing a Roux-Y gastric bypass procedure received single I-hour infusions of alatrofloxacin equivalent to 300mg of its active metabolite, trovafloxacin. Blood samples were obtained over a 24-hour period and adipose tissue from subcutaneous and deep tissue sites were obtained approximately 3 hours post-infusion of alatrofloxacin. Plasma and adipose tissue concentrations of trovafloxacin were determined by high pressure liquid chromatography with fluorescence detection. Results: The mean maximum plasma concentration, area under the concentration-time curve, and elimination half-life of trovafloxacin were 3.6 mg/L, 37.4 mg/L .h, and 12.1h, respectively. The mean tissue concentrations at the subcutaneous and deep adipose sites were 0.43 and 0.41 mug/g, respectively. Conclusions: These results indicated that the pharmacokinetics of trovafloxacin in morbidly obese individuals are similar to those in healthy control individuals. In addition, the concentrations of trovafloxacin achieved in the adipose tissue were above the minimum inhibitory concentration of most pathogens responsible for surgical and decubitus ulcer infections.