Nasal administration of low molecular weight heparin.
The main objective of this study was to determine if the systemic absorption of therapeutic amounts of heparin was possible following nasal administration. Sprague-Dawley rats received nosedrops containing a low molecular weight heparin (LMWH) or unfractionated heparin (UFH) formulated with or without tetradecylmaltoside (TDM). TDM is a nonionic surfactant that has been previously shown to be a potent absorption enhancer in studies with peptide drugs. LMWH/UFH absorption was determined by measuring plasma anti-Factor Xa activity. The inclusion of 0.25% TDM in nasal formulations containing LMWH resulted in a significant increase in the C(max) and area under the curve (AUC) of anti-Factor Xa activity when compared to LMWH formulated in saline alone. The addition of TDM to a nasal formulation containing UFH resulted in a much smaller increase in the C(max) and the AUC of anti-Factor Xa activity. The absolute bioavailability of LMWH was increased from 4.0 +/- 0.4% in the absence of TDM to 19 +/- 0.3% in the presence of TDM. The reversibility of the absorption enhancing effect of TDM was studied by applying LMWH nasally 60 or 120 min after the enhancer. The effect of TDM on the nasal epithelia appeared to be rapidly reversible. In conclusion, nasal delivery of LMWH, but not UFH, was successful when an absorption enhancer was included to increase nasal permeability.
Arnold
John
J
Department of Pharmacology and Toxicology, School of Medicine, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, Alabama 35294-0019, USA.
Ahsan
Fakhrul
F
Meezan
Elias
E
Pillion
Dennis J
DJ
D000281:Administration, Intranasal; D000818:Animals; D002626:Chemistry, Pharmaceutical; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D008320:Maltose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009296:Nasal Cavity / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D006495:Heparin, Low-Molecular-Weight; C459187:tetradecyl maltoside; D008320:Maltose