PMID- 12115833
OWN - NLM
STAT- MEDLINE
DCOM- 20021211
LR  - 20071114
IS  - 0022-3549 (Print)
IS  - 0022-3549 (Linking)
VI  - 91
IP  - 7
DP  - 2002 Jul
TI  - Nasal administration of low molecular weight heparin.
PG  - 1707-14
AB  - 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.
CI  - Copyright 2002 Wiley-Liss Inc.
FAU - Arnold, John
AU  - Arnold J
AD  - Department of Pharmacology and Toxicology, School of Medicine, University of 
      Alabama at Birmingham, 1670 University Boulevard, Birmingham, Alabama 35294-0019, 
      USA.
FAU - Ahsan, Fakhrul
AU  - Ahsan F
FAU - Meezan, Elias
AU  - Meezan E
FAU - Pillion, Dennis J
AU  - Pillion DJ
LA  - eng
GR  - ES08933/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharm Sci
JT  - Journal of pharmaceutical sciences
JID - 2985195R
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (tetradecyl maltoside)
RN  - 69-79-4 (Maltose)
SB  - IM
MH  - Administration, Intranasal
MH  - Animals
MH  - Chemistry, Pharmaceutical
MH  - Heparin, Low-Molecular-Weight/*administration & dosage/*pharmacokinetics
MH  - Male
MH  - Maltose/administration & dosage/*analogs & derivatives/pharmacokinetics
MH  - Nasal Cavity/drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2002/07/13 10:00
MHDA- 2002/12/12 04:00
CRDT- 2002/07/13 10:00
PHST- 2002/07/13 10:00 [pubmed]
PHST- 2002/12/12 04:00 [medline]
PHST- 2002/07/13 10:00 [entrez]
AID - S0022-3549(16)31030-9 [pii]
AID - 10.1002/jps.10171 [doi]
PST - ppublish
SO  - J Pharm Sci. 2002 Jul;91(7):1707-14. doi: 10.1002/jps.10171.