Background: The interest in administering drugs by intranasal route is currently increasing,
particularly because it has shown to ensure drug therapeutic action by a rapid systemic
absorption through the respiratory mucosa and/or a direct delivery of some molecules into the
brain through the olfactory mucosa. Nevertheless, although intranasal administration avoids the
first-pass hepatic biotransformation, several enzymes as well as efflux transporters can be found
in the mammalian nasal epithelium.
Methods: This work reviewed the expression and localization of the drug-metabolizing enzymes
and efflux transporters in the mammalian nasal mucosa epithelium, as well as their influence on
the pharmacokinetic and pharmacodynamic profiles of specific drugs, using one hundred and
thirty five peer-reviewed papers undertaken from MEDLINE database, including review and
Results: Most of the studies analyzed corroborate that oxidative and conjugative enzymes as well as multidrug resistance
proteins and multidrug resistance-associated proteins efflux transporters are expressed in the nasal cavity, particularly
in olfactory and respiratory mucosae, determining the access of drugs to central nervous system and bloodstream.
Nonetheless, besides their well-documented anatomic location, either in laboratory animals or humans, there is
still a lack of experimental information regarding the substrates of these enzymes and efflux transporters at the nasal
Conclusion: The knowledge herein discussed important not only to select the drugs with better potential to be administered
by intranasal route but also to optimize drug formulations, in which inhibitors of enzymes or efflux transporters
may be included to increase drug systemic and central delivery.