Study on the metabolic fate of catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc]. 1st communication: absorption, distribution, metabolism and excretion after single administration to rats

Arzneimittelforschung. 1991 Sep;41(9):965-75.

Abstract

Studies on the absorption, distribution, metabolism and excretion of 14C-Z-103 and 65Zn-Z-103 (catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7) were performed after oral administration to rats. After oral administration of 14C-Z-103 and 65Zn-Z-103, the blood concentrations of 14C-radioactivity were 30- to 40-fold higher than those of 65Zn-radioactivity. The 14C-radioactivity showed a dose-dependent increase of Cmax and AUC values in the dose range from 13.1 mg/kg to 100 mg/kg, and remained longer in the blood. In contrast, no dose-dependent increase of AUC was observed with 65Zn-radioactivity, suggesting saturation of absorption at doses more than 30 mg/kg of 65Zn-Z-103. The major route of excretion of 14C-radioactivity was by excretion into the expired air, amounting to 38.8% of the administered dose, while the urinary and fecal excretions were low values at 4.1% and 13.3%, respectively. The radioactivity remaining in the carcass accounted for 39.3% of the dose. On the other hand, in the case of 65Zn-radioactivity, 85.0% of the administered dose was excreted into the feces and 10.5% of the dose remained in the carcass. Both 14C- and 65Zn-radioactivities were distributed to the whole body, while 14C-radioactivity showed higher concentrations in the body, and was retained longer than the 65Zn-radioactivity. When the plasma and the liver and kidney homogenates, from rats received 14C-Z-103, were treated with trichloroacetic acid (TCA), the radioactivities in the TCA-insoluble fraction increased as a function of time. Following the treatment of the homogenates with protease, the radioactivities in the TCA-insoluble fraction decreased. In vitro study was showed that L-carnosine of 14C-Z-103 added to the homogenates of liver and small intestine was metabolized to L-histidine. The results suggest that the remaining radioactivities in tissues and organs caused the incorporation of the metabolites of 14C-Z-103 into endogenous high molecular substances.

MeSH terms

  • Animals
  • Autoradiography
  • Bile / metabolism
  • Blood Proteins / metabolism
  • Carnosine / metabolism
  • Dipeptides / metabolism
  • Dipeptides / pharmacokinetics*
  • Feces / chemistry
  • Histidine / metabolism
  • Intestinal Absorption
  • Male
  • Organometallic Compounds / metabolism
  • Organometallic Compounds / pharmacokinetics*
  • Protein Binding
  • Rats
  • Rats, Inbred Strains
  • Tissue Distribution
  • Zinc Compounds
  • Zinc Radioisotopes

Substances

  • Blood Proteins
  • Dipeptides
  • Organometallic Compounds
  • Zinc Compounds
  • Zinc Radioisotopes
  • polaprezinc
  • Histidine
  • Carnosine