Effects of dose, pH and osmolarity on intranasal absorption of recombinant human erythropoietin in rats.
The effects of dose, pH and osmolarity on the intranasal absorption of a recombinant human erythropoietin (rEPO) solution were studied in male Wistar rats. The intranasal administration of rEPO was evaluated by measuring percentage circulating reticulocytes of red blood cells on a stained blood smear (smear method), and also by measuring residual circulating reticulocyte counts using a microcell counter (sysmex method). Both results suggest that rEPO solution was absorbed through the nasal mucosa of rats without enhancers after a single intranasal administration. The pharmacological availabilities of rEPO after intranasal administration compared with intravenous administration were about 7% and 4%, when estimated by smear method and sysmex method, respectively. The pharmacological activity was enhanced in low pH and hypotonic mannitol solution.
D000042:Absorption; D000281:Administration, Intranasal; D000818:Animals; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism*; D009994:Osmolar Concentration; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism
D011994:Recombinant Proteins; D004921:Erythropoietin