Nasal absorption of procyclidine in rats and dogs.
Nasal absorption of procyclidine, a synthetic anticholinergic compound, was investigated in Wistar rats and Beagle dogs. The dosing solution was prepared by dissolving 14C-procyclidine in 50% ethanolic saline. The dosing solution was administered intravenously and intranasally to rats at a dose of 0.6 mg/kg (i.e., 60 microl/kg in the form of a 1% w/v solution), and intravenously, orally and intranasally to dogs at a dose of 0.3 mg/kg (i.e., 6 microl/kg in the form of a 5% w/v solution). Blood samples were taken from an artery of the animals through the catheter for periods of 1200 (for rats) and 1,440 min (for dogs), and the radioactivity in the samples was determined by liquid scintillation counting. The nasal bioavailability of procyclidine in rats and dogs, based on the radioactivity, was calculated to be 81.1 and 98.6%, respectively. In both rats and dogs, the plasma profiles of procyclidine following nasal administration were very close to those following intravenous administration, leading to nearly superimposable profiles between the two protocols. In dogs, nasal administration resulted in significantly higher plasma concentrations during the first 30 min period compared to oral administration, suggesting the superiority of the nasal route over the oral route in terms of a prompt expression of the pharmacological effect of the drug. The results obtained in this study indicate that procyclidine is rapidly and nearly completely absorbed via the nasal route. In conclusion, nasal administration represents a viable alternative to intravenous administration in the case of procyclidine.
Jang
E J
EJ
Department of Pharmaceutics, College of Pharmacy, Seoul National University, Kwanak-gu, Seoul, Korea.
Lee
Y J
YJ
Chung
S J
SJ
Shim
C K
CK
D000042:Absorption; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D004285:Dogs; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009297:Nasal Mucosa / Q000378:metabolism*; D011352:Procyclidine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
D018727:Muscarinic Antagonists; D011352:Procyclidine