Residence time of polaprezinc (zinc L-carnosine complex) in the rat stomach and adhesiveness to ulcerous sites.
Polaprezinc, an insoluble zinc complex of L-carnosine, exhibits anti-ulcer effects by acting directly on mucosal lesions. The disposition of polaprezinc in the stomach was studied to clarify the usefulness of its structure as an insoluble complex. The time courses of 14C-radioactivity in the gastric contents and gastric tissues were parallel to those of 65Zn after oral administration of a mixture of 14C-polaprezinc and 65Zn-polaprezinc (14C-, 65Zn-polaprezinc) to rats. The gastric contents of 14C-polaprezinc and 65Zn-polaprezinc were greater than those of 14C-L-carnosine and 65ZnSO4. Mean residence times (MRT) of 14C-polaprezinc and 65Zn-polaprezinc in the stomach were almost the same (ca. 2 hr), and they were double those of 14C-L-carnosine and 65ZnSO4. In gastric tissues, the area under the concentration curves (AUC0-8 hr) of 14C-polaprezinc and 65Zn-polaprezinc were 1.7 times greater than those of 14C-L-carnosine and 65ZnSO4, respectively. After administration of 14C-, 65Zn-polaprezinc to rats with acetic acid-induced ulcers, 14C and 65Zn-radioactivities in the ulcerous sites were very similar and greater than those of 14C-, 65Zn-polaprezinc dissolved in acid. In conclusion, polaprezinc is retained in the stomach longer and adheres to the ulcerous sites more than zinc or L-carnosine. The characteristics of this compound may arise from its insolubility and contribute to its strong pharmacological action.
Furuta
S
S
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Toyama
S
S
Miwa
M
M
Itabashi
T
T
Sano
H
H
Yoneta
T
T
D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001665:Binding Sites; D002247:Carbon Isotopes; D002336:Carnosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005746:Gastric Emptying / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005766:Gastrointestinal Contents / Q000737:chemistry; D007553:Isotope Labeling; D008297:Male; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013276:Stomach Ulcer / Q000188:drug therapy / Q000378:metabolism*; D013431:Sulfates / Q000097:blood / Q000378:metabolism; D015032:Zinc / Q000378:metabolism; D017967:Zinc Compounds / Q000097:blood / Q000378:metabolism; D015037:Zinc Radioisotopes; D019287:Zinc Sulfate
D000897:Anti-Ulcer Agents; D002247:Carbon Isotopes; D009942:Organometallic Compounds; D013431:Sulfates; D017967:Zinc Compounds; D015037:Zinc Radioisotopes; C061957:polaprezinc; D019287:Zinc Sulfate; D002336:Carnosine; D015032:Zinc