Study on the metabolic fate of catena-(S)-[mu-[N alpha-(3-aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc]. 4th communication: disposition of zinc and amino acids in rats, dogs and monkeys.
The time course of the zinc plasma concentrations in rats, dogs and monkeys and the metabolic fate of L-carnosine were investigated after oral administration of Z-103 (catena-(S)-[mu-[N alpha-(3-aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7). There was no intradiurnal variation in the plasma concentrations of endogenous zinc in rats, dogs and monkeys. The plasma concentrations of endogenous zinc in dogs and monkeys were approximately the same as that in humans, whereas the plasma concentration of zinc in rats was 2.2-fold higher than that in man. After administration of Z-103 to non-fasted dogs at 100 mg/kg, the plasma concentration of zinc reached Cmax at 0.5 h after administration (1.7-fold higher than endogenous zinc level), while the plasma concentration was the lowest in comparison with other animal species. After administration to fasting rats at 50 mg/kg, the plasma concentration of zinc reached Cmax at 1 h after administration (2.5-fold higher than endogenous zinc level) and decreased thereafter, returning to the endogenous level at 8 h after administration. After oral administration to monkeys at 10 mg/kg and 50 mg/kg, the Cmax values were 4.1-fold and 6.8-fold higher than the endogenous level, respectively. The Tmax values were achieved at 4-6 h and 8 h after each administration, respectively, showing slower absorption in comparison with other animal species.(ABSTRACT TRUNCATED AT 250 WORDS)
Furuta
S
S
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Toyama
S
S
Miwa
M
M
Ikeda
Y
Y
Sano
H
H
Matsuda
K
K
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002336:Carnosine / Q000378:metabolism / Q000031:analogs & derivatives; D002851:Chromatography, High Pressure Liquid; D004151:Dipeptides / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D004285:Dogs; D008252:Macaca fascicularis; D008297:Male; D009942:Organometallic Compounds / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013054:Spectrophotometry, Atomic; D017967:Zinc Compounds; D015037:Zinc Radioisotopes
D000596:Amino Acids; D004151:Dipeptides; D009942:Organometallic Compounds; D017967:Zinc Compounds; D015037:Zinc Radioisotopes; C061957:polaprezinc; D002336:Carnosine