Disposition and metabolism of (14C)cadralazine in rats. (I). Single administration.

Fujii, Toshihiko; Mikuriya, Naoko; Furukawa, Hideo; Miyazaki, Hisashi; Kagemoto, Akira; Negoro, Toshiyuki; Sekine, Yutaka; Hashimoto, Masahisa; Tanaka, Keiichi

doi:10.2133/dmpk.2.587

Cited by 3 publications

(3 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Within 48 hours, excretion of unchanged (+)-OFLX in urine is 47.3, 49.9 and 62.3% dose in the rat, dog and monkey, respectively. In this conjunction, it is generally well-known that the ester glucuronidation reaction is the main metabolic pathway of quinolone antibacterial agents such as enoxacin (Fujii et al 1984), cinoxacin (Sugeno et al. 1980) and many other quinolones which commonly possess the carboxyl group at the 420 0.…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Metabolic Disposition of Enantiomers of Ofloxacin in Rats

1989

View full text Add to dashboard Cite

1. Stereoselective metabolic disposition of ofloxacin (OFLX) was studied in rats after oral administration of S-(-)-14C-OFLX and R-(+)-14C-OFLX at a dose of 20 mg/kg. 2. Radioactivity of the S-(-)-isomer was eliminated from blood much faster than that of the R-(+)-isomer. Marked differences in pharmacokinetic parameters exist between the enantiomers; the half life and AUC values of R-(+)-OFLX were greater than those of S-(-)-OFLX. Enantiomeric differences were also seen in the excretion of radioactivity, especially in biliary excretion. 3. 31.3 and 7.4% dose were excreted in the 8 h bile as ester glucuronides after oral administration of S-(-)- and R-(+)-OFLX, respectively. The enantiomeric difference in biliary excretion may be caused by stereoselective glucuronidation of S-(-)-OFLX to the ester glucuronide. 4. The metabolite pattern in serum and urine showed that the ester glucuronide of S-(-)-OFLX was more predominant than that of R-(+)-OFLX. 5. The stereoselective ester glucuronidation of the S-(-)-isomer in rats may induce significant differences in the pharmacokinetic parameters of S-(-)- and R-(+)-OFLX.

show abstract

Section: Introductionmentioning

confidence: 99%

Stereoselective Metabolic Disposition of Enantiomers of Ofloxacin in Rats

1989

View full text Add to dashboard Cite

show abstract

“…Oral administration was done at doses of 2−1000 mg/ 1.85−3.7 MBq/kg with a stomach tube. Unless otherwise specified, methods and conditions for animal experiments were essentially the same as described previously [11,12]: They involve procedures for collection of biological samples such as blood, tissues, urine and feces. In the expiratory excretion study, 14 CO 2 in expired air was trapped in 25 % aminoethanol solution.…”

Section: Animal Experimentsmentioning

confidence: 99%

“…The trapping solution of the expired air was directly mixed with a scintillation cocktail, Clear-sol I (Nacarai Tesque, Kyoto, Japan). Radioactivity of other biological samples was measured as reported previously [11,12] in a liquid scintillation counter (Tri-Carb 2000CA, 2200CA and 2700TA; Packard, Meriden, CT, USA) with correction for counting efficiency by external gamma standardization. If the standard deviation of the sample radioactivity counts (cpm) exceeded 5 % of the counts, its sample radioactivity was defined to be below the reliable limit of measurement (BRL).…”

Section: Measurement Of Radioactivitymentioning

confidence: 99%

Disposition of Exogenous Urea and Effects of Diet in Rats

Nomura

Matsumoto

Nishimura

et al. 2011

Arzneimittelforschung

Self Cite

View full text Add to dashboard Cite

Although breath test using 13C-labeled urea (CAS 57-13-6, UBT) is becoming popular for the diagnosis of Helicobacter pylori (H. pylori) infection, disposition of exogenously given urea is not fully understood. The purpose of the present study is to elucidate the disposition of exogenous urea and to consider its relation with the UBT safety and biobehavior of endogenous urea. With 14C-labeled urea ([14C]urea), the absorption, distribution, metabolism and excretion including that into breathed air after its administration in trace to large doses in rats were investigated. [14C]Urea was given to fasted and non-fasted rats through intravenous and oral routes. It was found that the disposition of exogenous [14C]urea behaves in a similar way as endogenous urea, and a sufficiently large capacity for disposing urea in rats was suggested from the linear pharmacokinetics within the wide dose range of [14C]urea (2-1000 mg/kg). The safety of urea in UBT was also revealed by consideration of its dose and human urea body pool. It was also suggested that diet stimulates both systemic (as observed after the intravenous dose) and pre-systemic (as with the oral route) decompositions of urea into carbon dioxide and ammonia, but does not affect the renal elimination and distribution pattern in rat tissues. The findings in this study provide us with the quantitative information concerning not only the safety and disposition of urea as a diagnostic agent, but also the biobehavior of endogenous urea in ureotelism.

show abstract