Regular ArticleNasal Cytochrome P450 2A: Identification, Regional Localization, and Metabolic Activity toward Hexamethylphosphoramide, a Known Nasal Carcinogen
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Nasal accumulation and metabolism of Δ<sup>9</sup>-tetrahydrocannabinol following aerosol (‘vaping’) administration in an adolescent rat model
2023, Pharmacological ResearchCitation Excerpt :This finding is novel, but not completely unexpected. Previous research showed that rat nasal mucosa and lungs express various cytochrome P450 isoforms [31,32] which catalyze this reaction [33-35]. THC biotransformation in nasal mucosa is likely to be functionally relevant because the maximal concentrations reached by 11-OH-THC in the nasal cavity were sizeable (double-digit micromolar) and approximately 80 times higher than those found in plasma.
Advanced formulations for intranasal delivery of biologics
2018, International Journal of PharmaceuticsCitation Excerpt :After the administration, the initial glucose blood concentration was decreased by 40% for 4–5 h (Wu et al., 2007). Although there are only few reports available on human nasal metabolism, these observations strongly suggest the presence of significant metabolic activity on human nasal mucosa (Sarkar, 1992). The degree of degenerative enzymes is comparable low in reference to the gastro-intestinal tract, however as inactivation of therapeutics can quickly take place, they might dramatically decrease systemic bioavailability.
A Tuned Bicyclic Proazaphosphatrane for Catalytically Enhanced N-Arylation Reactions with Aryl Chlorides
2015, European Journal of Organic ChemistryDistribution of α-asarone in brain following three different routes of administration in rats
2014, European Journal of Pharmaceutical SciencesCitation Excerpt :Intranasal administration can avoid the side effects caused by the first-pass metabolism when the drug is administered orally. Although drugs might not escape entirely from metabolic effects because of enzymes such as cytochrome P450 enzymes in the intranasal environment (Thornton-Manning et al., 1997; Zhang et al., 2005), reducing this effect is very important for drugs that are strongly impaired by the significant first pass metabolism, such as verapamil HCl (Abdel Mouez et al., 2014), rivastigmine (Yang et al., 2013), and zolmitriptan (Vyas et al., 2005). The particle-size distribution of the α-asarone powder was very heterogeneous, with both large and small particles, and it is well known that particles with diameters between 2 and 5 μm can deposit in the lungs.
Intranasal administration of opioids/fentanyl - Physiological and pharmacological aspects
2010, European Journal of Pain SupplementsBioactivation of coumarin in rat olfactory mucosal microsomes: Detection of protein covalent binding and identification of reactive intermediates through analysis of glutathione adducts
2009, Chemico-Biological InteractionsCitation Excerpt :Forming a barrier between the external environment of the nasal cavity and the systemic circulation and adjacent brain tissue, the mammalian olfactory mucosa (OM) is unique relative to many other tissues in drug metabolism and toxicity perspectives, due to the presence of tissue-predominant (e.g., human CYP2A13, rat CYP2A3, mouse CYP2A5) and tissue-specific (e.g., rat and mouse CYP2G1) cytochrome P450s (CYPs) at a high expression level (pmol/mg protein) (reviewed in [1–3]). Teamed with high contents of NADPH-cytochrome P450 reductase (CPR) in the tissue, OM displays a substantial metabolic capacity toward endogenous steroids (e.g. testosterone and progesterone) [4,5] and a growing list of inhaled or systemically exposed olfactory toxicants and procarcinogens, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 2,6-dichlorobenzonitrile, acetaminophen (AP), coumarin, hexamethylphosphoramide and 2,6-diclorophenyl methylsulfone [2,6–11]. The high metabolic turnover rate in OM is generally believed to maintain homeostasis of the chemosensory tissue and protect the adjacent brain tissue from environmental insults [12].
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To whom correspondence should be addressed. Fax: (505) 845-1198.
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Present address: Dept. of Pathology, Michigan State University, College of Veterinary Medicine A46, East Lansing, MI 48824.