Evaluation of effect of ephedrine on the transport of drugs from the nasal cavity to the systemic circulation and the central nervous system.
It has been shown that vasoconstrictive drugs such as ephedrine derivatives are able to decrease systemic absorption of drugs administered by mucosal surfaces. The present paper set out to evaluate in the rat model the effect of co-administered nasal ephedrine on the absorption of GR138950 in a simple and in a pectin self-gelling formulation. It was hypothetised that a decrease in nasal systemic absorption would lead to an increase in direct nose-to-brain transport as demonstrated by the drug concentration in the olfactory lobes of the brain. It was found that ephedrine administered nasally with the drug in a simple aqueous solution resulted in a significant increase in nasal systemic absorption and also an increase in brain delivery; however, this trend was not observed with the pectin formulations. The pectin formulation with ephedrine resulted in lower systemic absorption of GR138950 and lower brain uptake compared to the simple solution formulation containing ephedrine.
Charlton
Stuart T
ST
The School of Pharmacy, University of Nottingham, University Park, Nottingham, UK.
Davis
Stanley S
SS
Illum
Lisbeth
L
D000281:Administration, Intranasal; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D001572:Benzofurans / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D001692:Biological Transport / Q000187:drug effects; D002490:Central Nervous System / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004809:Ephedrine / Q000008:administration & dosage / Q000494:pharmacology*; D005782:Gels; D008297:Male; D015394:Molecular Structure; D009296:Nasal Cavity / Q000378:metabolism*; D009830:Olfactory Bulb / Q000378:metabolism; D010368:Pectins / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012996:Solutions; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology; D014867:Water
D047228:Angiotensin II Type 1 Receptor Blockers; D001572:Benzofurans; D005782:Gels; D012996:Solutions; D014662:Vasoconstrictor Agents; D014867:Water; D010368:Pectins; D004809:Ephedrine; C089586:saprisartan potassium