[Tissue and aural discharge distribution of tebipenem pivoxil].
Tebipenem pivoxil (TBPM-PI) is a novel oral carbapenem antibiotic. It has been developed as a prodrug of tebipenem (TBPM), to increase absorption. We assessed the distribution of TBPM to aural discharge and tissues after administration of TBPM-PI to adult patients who underwent otolaryngological surgical tissue resection and pediatric patients with acute otitis media or acute sinusitis. Following the administration of single oral doses of 150 and 250 mg (potency) of TBPM-PI to adult patients who underwent otolaryngological surgical tissue resection, tissue TBPM concentrations for the respective doses were 0.38 to 1.76 microg/g and 0.17 to 0.91 microg/g in mucous membranes of the maxillary sinus, 0.26 to 0.94 microg/g and 0.14 to 0.45 microg/g in mucous membranes of the ethmoid sinus, and 0.12 to 0.13 microg/g and 0.14 to 0.47 microg/g in palatine tonsil tissues, as well as 0.29 microg/g in mucous membranes of the middle ear for the dose of 250 mg. The percentages of these tissue concentrations to plasma concentrations for the respective doses were 14.3% to 61.0% and 18.4% to 54.6% in mucous membranes of the maxillary sinus, 34.3% to 52.1% and 9.9% to 54.6% in mucous membranes of the ethmoid sinus, and 10.3% to 15.0% and 6.5% to 17.4% in palatine tonsil tissues, as well as 16.8% in mucous membranes of the middle ear for the dose of 250 mg. Following the administration of TBPM-PI at doses of 4 mg (potency)/kg and 6 mg (potency)/kg twice daily to pediatric patients with acute otitis media or acute sinusitis, TBPM concentrations in the aural discharge for these doses were 0.03 to 2.00 microg/g and 1.07 or 1.18 microg/g, respectively. The percentage of aural discharge concentrations to plasma concentrations for these doses was 0.3% to 86.1% and 40.5% or 83.6%, respectively. These results indicate a favorable distribution profile of TBPM to tissues affected by otitis media or sinusitis after the administration of TBPM-PI and can support the high efficacy of TBPM-PI.
Baba
Shunkichi
S
Nagoya City University Medical School.
Kasahara
Hiroshi
H
Morita
Jun
J
Aizawa
Kazumasa
K
Sunakawa
Keisuke
K
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D015780:Carbapenems / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004432:Ear, Middle / Q000378:metabolism*; D005122:Exudates and Transudates / Q000378:metabolism*; D006504:Hepatic Veno-Occlusive Disease; D006801:Humans; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D010033:Otitis Media / Q000378:metabolism; D055815:Young Adult
D015780:Carbapenems; C500135:tebipenem