Telithromycin のマウス, ラットおよびイヌにおける薬物動態学的研究

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The studies on absorption, distribution, metabolism and excretion of telithromycin (TEL) were carried out in mouse, rat and dog using 14C-TEL. Absorption rates after oral dosing were 47% in mouse and rat, 83% in dog, and bioavailability in these animals were 53, 36 and 54%, respectively. The first pass effect observed was low and moderate in rat and dog respectively, but none observed in mouse. Tmax of these animals were from 0.25 to 2 h, and suggested that TEL will be absorbed from small intestine to large intestine. The volume of distribution in mouse, rat and dog after intravenous dosing were 1.41, 10.62 and 4.9 L/kg, respectively, and total clearance of these animals were 0.80, 4.36 and 1.5 L/h/kg, respectively. The terminal plasma half-life of these animals were form 1.2 to 2.3 h. After single oral administration of doses ranging between 5 and 20mg/kg in rat, Cmax and AUC were increased dose dependently, but these increments were more than the dose-ratio and indicated a non linear pharmacokinetic profile. In rats after oral dosing, higher concentration of radioactivity in most of the tissues was measured than that in plasma, except for central nervous system. All of the radioactivity found in tissues were rapidly decreased from 6h after administration, and almost total elimination of radioactivity from the body's tissues were observed within 24 h of administration. Throughout the study, the fact that high concentration of radioactivity was detected in intestinal wall suggested probable secretion of radioactivity from the blood compartment to the lumina of the gastrointestinal tract. In vitro serum protein binding studies, TEL was bound to mouse serum protein about 90%, but was weakly bound to that of rat and dog (less than 70%). In the studies rat and dog, TEL accounted for 70.7-72.5% of plasma radioactivity in rat and dog. Its metabolites in plasma of rat were below the limit of quantification (0.005 mg eq./L), but in dog plasma, RU 76584 (N-oxidepyridine)
公益社団法人日本化学療法学会の論文
2003-09-30

Telithromycin のマウス, ラットおよびイヌにおける薬物動態学的研究

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