Study on the metabolic fate of catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc]. 2nd communication: absorption, distribution, metabolism and excretion after repeated administration to rats.
After repeated administration of 14C-Z-103 (catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7) to rats for 21 days, the accumulation of radioactivity in the blood and tissues was proportional to the number of doses given. Following treatment of the terminal blood, plasma, liver and kidney samples with trichloroacetic acid (TCA) or protease, the radioactivity in these tissues was demonstrated to be TCA-insoluble and solubilized by the protease treatment. Thus, the accumulation of radioactivity after repeated administration of 14C-Z-103 was considered to be due to the utilization of the metabolites of L-carnosine, the constituent of Z-103, into a protein. The cumulative ratios of radioactivity excreted into the urine, feces and expired air and the radioactivity remaining in the carcass after repeated administration of 14C-Z-103 for 21 days were similar to those values obtained after a single administration, suggesting that repeated administration did not influence the excretion profile of Z-103. During the period of repeated administration of non-radioactive Z-103 to rats for 21 days, the fecal content of zinc was higher than that in nontreated rats, whereas it returned to the control level at 48 h after the final administration. There was no significant difference in the urinary concentration of zinc between treated and non-treated animals during the period of repeated administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Toyama
S
S
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Furuta
S
S
Miwa
M
M
Suzuki
M
M
Sano
H
H
Matsuda
K
K
D000042:Absorption; D000818:Animals; D001345:Autoradiography; D002245:Carbon Dioxide / Q000378:metabolism; D002336:Carnosine / Q000378:metabolism / Q000031:analogs & derivatives; D002855:Chromatography, Thin Layer; D004151:Dipeptides / Q000378:metabolism / Q000493:pharmacokinetics*; D005243:Feces / Q000737:chemistry; D006639:Histidine / Q000378:metabolism; D008297:Male; D009942:Organometallic Compounds / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D017967:Zinc Compounds; D015037:Zinc Radioisotopes
D004151:Dipeptides; D009942:Organometallic Compounds; D017967:Zinc Compounds; D015037:Zinc Radioisotopes; C061957:polaprezinc; D002245:Carbon Dioxide; D006639:Histidine; D002336:Carnosine