Flomoxef is used to treat bacterial prostatitis; however, its prostatic pharmacokinetics have not been fully clarified. Flomoxef (500 or 1000 mg) was administered to patients with benign prostatic hypertrophy (n = 54). After a 0.5-h infusion, venous blood samples were drawn at time points of 0.5-5 h, and prostate tissue samples were collected at time points of 0.5-1.5 h during transurethral resection of the prostate. The drug concentrations in plasma and prostate tissue were analyzed pharmacokinetically and used for a stochastic simulation to predict the probability of attaining pharmacodynamic target in prostate tissue. Showing dose linearity in the prostatic pharmacokinetics, flomoxef rapidly penetrated into prostate tissue, with a prostate/plasma ratio of 0.48-0.50 (maximum drug concentration) and 0.42-0.55 (area under the drug concentration-time curve). Against the tested populations of Escherichia coli, Klebsiella and Proteus species isolates, 0.5-h infusion of 1000 mg three times daily achieved a ≥90% expected probability of attaining the bactericidal target (70% of the time above the minimum inhibitory concentration [MIC]) in prostate tissue. The site-specific pharmacodynamic-based breakpoint (the highest MIC at which the target-attainment probability in prostate tissue was >90%) values were 0.25 mg/L (MIC for 90th percentile of E. coli and Klebsiella species) for 500 mg four times daily and 0.5 mg/L (MIC90 of Proteus species) for 1000 mg four times daily. These results help to fully characterize the prostatic pharmacokinetics of flomoxef, while also helping to rationalize and optimize the dosing regimens for prostatitis based on site-specific pharmacodynamic target attainment.
Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2019 Dec 07 [Epub ahead of print]
Kogenta Nakamura, Kazuro Ikawa, Genya Nishikawa, Ikuo Kobayashi, Motoi Tobiume, Miho Sugie, Hiroyuki Muramatsu, Shingo Morinaga, Keishi Kajikawa, Masahito Watanabe, Kent Kanao, Tetsushu Onita, Norifumi Morikawa
Department of Urology, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan., Department of Clinical Pharmacotherapy, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. Electronic address: ., Department of Urology, Asahi Rousai Hospital, Nagoya, Aichi, 488-8585, Japan., Department of Clinical Pharmacotherapy, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.