ABSTRACT
Physostigmine, an acetyl cholinesterase inhibitor, and arecoline, a muscarinic agonist, have been shown to improve Alzheimer presenile dementia in some patients when administered parenterally. Both of these compounds are ineffective orally due to first-pass metabolism. The nasal route was examined as an alternative route of administration for both drugs. Nasal bioavailabilities and dispositions for both drugs were determined in rats. Physostigmine nasal bioavailability was 100% as compared with iv bioavailability, and that of arecoline was 85% when compared with bioavailability following im administration.
Subject(s)
Arecoline/pharmacokinetics , Nasal Mucosa/metabolism , Physostigmine/pharmacokinetics , Absorption , Administration, Intranasal , Animals , Arecoline/administration & dosage , Biological Availability , Half-Life , Injections, Intravenous , Male , Physostigmine/administration & dosage , RatsABSTRACT
Cold analytical methodology is usually available for drug and metabolite monitoring during clinical trials, since a procedure is required for the bioavailability, pharmacokinetic, and dose proportionality studies that must be conducted by the sponsor. Such methods can and have been applied to monitoring patient compliance. Examples from several classes of drugs with different pharmacokinetic profiles illustrate the type of data that can be obtained, along with their applicability and inherent limitation in assessing compliance. The effects of concomitant medication, drug half-life, volume of distribution, and sampling time on observed levels are also discussed. Several other approaches involving trace metals, microtaggants, and an electronic monitor are also presented.
