Absorption mechanism of polaprezinc (zinc L-carnosine complex) by an everted sac method.
1. The absorption mechanism of polaprezinc (zinc-carnosine chelate compound) was studied in rat by an everted gut sac method. The rates of transport and accumulation of 14C-L-carnosine were proportional to the mucosal concentration of L-carnosine, whereas the rates of transport and accumulation of 65ZnCl2 had become saturated. The Michaelis-Menten constant (Km) = 4.41 mM and maximal rate (Vmax) = 71.83 nmol/min/g for zinc transport and, similarly, Km = 6.21 mM and Vmax = 92.51 mumol/30 min/g for accumulation. 2. The addition of ouabain, 2,4-dinitrophenol (2,4-DNP) and low temperatures reduced the rate of zinc uptake, indicating that zinc transport was considered to be a carrier-mediated process based on Na+,K(+)-ATPase-dependent mechanisms. 3. The concentration of zinc in the gut of the non-fasted rat was greater than that of the fasted rat, suggesting different rates of transport and accumulation. It is suggested that zinc intestinal uptake in rat is regulated by zinc content in the gut. 4. A pharmacokinetic model for transport and accumulation of zinc saturation from the lumen side to the gut was designed, and the calculated values obtained by simultaneous multiline fitting of transport and accumulation of zinc data were in good agreement with the observed values.
Furuta
S
S
Central Research Laboratories, Zeria Pharmaceutical Co. Ltd., Saitama, Japan.
Toyama
S
S
Sano
H
H
D000818:Animals; D001692:Biological Transport; D002250:Carbon Radioisotopes; D002336:Carnosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D003300:Copper / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000737:chemistry; D008297:Male; D008722:Methods; D009942:Organometallic Compounds / Q000378:metabolism / Q000493:pharmacokinetics*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature; D015032:Zinc / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D017967:Zinc Compounds; D015033:Zinc Isotopes
D002250:Carbon Radioisotopes; D004140:Dinitrophenols; D009942:Organometallic Compounds; D017967:Zinc Compounds; D015033:Zinc Isotopes; C061957:polaprezinc; D010042:Ouabain; D003300:Copper; D002336:Carnosine; D015032:Zinc