Intranasal absorption of buprenorphine--in vivo bioavailability study in sheep.
The bioavailability of buprenorphine, HCl (BPP) in sheep after nasal administration of two formulations has been studied. 0.9 mg BPP in 150 microl was administered nasally and compared to 0.6 mg i.v. The test solutions were formulated with 30% polyethylene glycol 300 (PEG 300) and 5% dextrose, respectively. The bioavailability for PEG 300 was 70% (S.D.+/-27%, n=6), whereas the bioavailability for 5% dextrose was 89% (S.D.+/-23%, n=6). A two-compartment model with initial and terminal serum half-lives of 10 and 23 min, respectively, may describe the pharmacokinetics. The rate of absorption for both nasal formulations was very fast (t(max)=10 min). The C(max) was 37 ng/ml (S.D.+/-17) and 48 (S.D.+/-10) for PEG 300 and dextrose, respectively. No significant difference was found between the two formulations, but PEG 300 has advantages in relation to freezing point depression and solubility, which may be considered if further studies are going to be initiated. The high nasal bioavailability and short time to maximal plasma concentration suggests that it is possible to make a clinically relevant nasal formulation of BPP for the treatment of pain.
Lindhardt
K
K
Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Ravn
C
C
Gizurarson
S
S
Bechgaard
E
E
D000281:Administration, Intranasal; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D002047:Buprenorphine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009296:Nasal Cavity / Q000378:metabolism*; D012756:Sheep
D000701:Analgesics, Opioid; D002047:Buprenorphine