Nasal absorption of desmopressin in rats and sheep. Effect of a bioadhesive microsphere delivery system.
The nasal absorption of desmopressin was studied in two animal models, the rat and the sheep. The bioavailability after nasal administration was found to be 13 times higher in the rat model. This discrepancy is suggested to be due to the impaired mucociliary clearance mechanism in the rat model and possibly differences in enzymatic degradation and elimination rates of the drug. The effect of the addition of L-alpha-lysophosphatidylcholine (LPC) to the formulations as an absorption enhancer was most pronounced in the sheep model. The use of the bioadhesive starch microsphere delivery system, especially in combination with LPC, had a profound effect on the absorption of desmopressin in sheep, with bioavailabilities reaching nearly 10% compared with 1.2% for a simple nasal solution of desmopressin.
Critchley
H
H
Department of Pharmaceutical Sciences, Nottingham University, University Park, UK.
Davis
S S
SS
Farraj
N F
NF
Illum
L
L
D000042:Absorption / Q000187:drug effects; D000281:Administration, Intranasal; D000818:Animals; D001682:Biological Availability; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008297:Male; D008863:Microspheres; D009297:Nasal Mucosa / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D012756:Sheep; D013213:Starch
D008244:Lysophosphatidylcholines; D013213:Starch; D003894:Deamino Arginine Vasopressin