Intranasal bioavailability of diazepam in sheep correlated to rabbit and man.
The purposes of the present study were to estimate the nasal bioavailability of diazepam in sheep and to compare this to earlier results in rabbits and humans. Additional, to compare the absorption during various initial periods in the two animal models and man, due to the importance of early absorption in emergency treatment. In a cross-over design, diazepam was nasally administered (7 mg) and intravenously (3 mg), respectively, to six sheep. Diazepam was solubilised in polyethylene glycol 300 in the nasal formulation. The mean nasal bioavailability, t(max) and C(max) were 15% (S.D.+/-8), 5 min (S.D.+/-3) and 934 ng/ml (S.D.+/-593), respectively. Sheep bioavailability was lower than rabbit 54% (P<0.001) and man 34% (P<0.05). In conclusion, the nasal absorption of diazepam was found to be fast, indicating the potential of nasal delivery in acute treatment. The initial (30 min) nasal bioavailability (30 min) for sheep and rabbit is a factor of 2.3 lower and 1.6 higher than man, respectively. The correlation of bioavailability was not optimal between sheep, man and rabbit with differences both in relation to extend and rate.
Lindhardt
Karsten
K
Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, 2100, Copenhagen, Denmark.
Olafsson
David R
DR
Gizurarson
Sveinbjörn
S
Bechgaard
Erik
E
D000281:Administration, Intranasal; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D003975:Diazepam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D011817:Rabbits; D012756:Sheep
D014151:Anti-Anxiety Agents; D003975:Diazepam