Disposition of exogenous urea and effects of diet in rats.
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.
Nomura
Naruaki
N
Drug Metabolism & Pharmacokinetics Group, Pharmacokinetics Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan. naruaki-nomura@dainippon-pharm.co.jp
Matsumoto
Satoshi
S
Nishimura
Yuka
Y
Terauchi
Yoshiaki
Y
Fujii
Toshihiko
T
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D001944:Breath Tests; D004032:Diet; D005215:Fasting; D005243:Feces / Q000737:chemistry; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014508:Urea / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*
D014508:Urea