AAPS PharmSciTech

, Volume 14, Issue 1, pp 60–63 | Cite as

Correlation between Nasal Membrane Permeability and Nasal Absorption Rate

  • Hefei Zhang
  • Chih-Wei Lin
  • Maureen D. Donovan
Rapid Communication


The objective of this study was to investigate the relationship between in vitro permeability (P app) values obtained from isolated nasal tissues and the absorption rates (k a) of the same compounds following nasal administration in animals and humans. The P app of a set of 11 drug compounds was measured using animal nasal explants and plasma time–concentration profiles for each of the same compounds following intravenous (IV) and intranasal (IN) administration were experimentally determined or obtained from literature reports. The plasma clearance was estimated from the IV plasma time–concentration profiles, and k a was determined from the IN plasma time–concentration profiles using a deconvolution approach. The level of correlation between P app and k a was established using Pearson correlation analysis. A good correlation (r = 0.77) representing a point-to-point relationship for each of the compounds was observed. This result indicates that the nasal absorption for many drug candidates can be estimated from a readily measured in vitro P app value.

Key words

bioavailability drug transport nasal administration nasal mucosa permeability 


  1. 1.
    Behl CR, Pimplaskar HK, Sileno AP, DeMeireles J, Romeo VD. Effects of physicochemical properties and other factors on systemic nasal drug delivery. Adv Drug Deliv Rev. 1998;29(1–2):89–116.PubMedCrossRefGoogle Scholar
  2. 2.
    Christiane SM, Peter H, Lang SR, Ditzinger G, Merkle HP. In vitro cell models to study nasal mucosal permeability and metabolism. Adv Drug Deliv Rev. 1998;29(1–2):51–79.Google Scholar
  3. 3.
    Fagerholm U. Prediction of human pharmacokinetics—gastrointestinal absorption. J Pharm Pharmacol. 2007;59(7):905–16.PubMedCrossRefGoogle Scholar
  4. 4.
    Veng-Pedersen P. Noncompartmentally-based pharmacokinetic modeling. Adv Drug Deliv Rev. 2001;48(2–3):265–300.PubMedCrossRefGoogle Scholar
  5. 5.
    Wadell C, Bjork E, Camber O. Permeability of porcine nasal mucosa correlated with human nasal absorption. Eur J Pharm Sci. 2003;18(1):47–53.PubMedCrossRefGoogle Scholar
  6. 6.
    Yuasa H, Iga T, Hanano M, Watanabe J. Relationship between in vivo first-order intestinal absorption rate constant and the membrane permeability clearance. J Pharm Sci. 1989;78(11):922–4.PubMedCrossRefGoogle Scholar
  7. 7.
    Usansky HH, Sinko PJ. Estimating human drug oral absorption kinetics from Caco-2 permeability using an absorption–disposition model: model development and evaluation and derivation of analytical solutions for k a and F a. J Pharmacol Exp Ther. 2005;314(1):391–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Chemuturi NV, Hayden P, Klausner M, Donovan MD. Comparison of human tracheal/bronchial epithelial cell culture and bovine nasal respiratory explants for nasal drug transport studies. J Pharm Sci. 2005;94(9):1976–85.PubMedCrossRefGoogle Scholar
  9. 9.
    Jansson B. Models for the transfer of drugs from the nasal cavity to the central nervous system. Dissertation. Uppsala, Sweden: University of Uppsala; 2004Google Scholar
  10. 10.
    Kandimalla KK, Donovan MD. Carrier mediated transport of chlorpheniramine and chlorcyclizine across bovine olfactory mucosa: implications on nose-to-brain transport. J Pharm Sci. 2005;94(3):613–24.PubMedCrossRefGoogle Scholar
  11. 11.
    Maitani Y, Ishigaki K, Takayama K, Nagai T. In vitro nasal transport across rabbit mucosa—effect of oxygen bubbling, pH and hypertonic pressure on permeability of lucifer yellow, diazepam and 17 beta-estradiol. Int J Pharm. 1997;146(1):11–9.CrossRefGoogle Scholar
  12. 12.
    Zhang H. Identification of membrane transporters to facilitate intranasal drug delivery using tissue-based and pharmacokinetic approaches. Dissertation. Iowa City, Iowa: University of Iowa; 2009Google Scholar
  13. 13.
    Chou K-J, Donovan MD. Distribution of antihistamines into the CSF following intranasal delivery. Biopharm Drug Dispos. 1997;18(4):335–46.PubMedCrossRefGoogle Scholar
  14. 14.
    Chou K-J, Donovan MD. The distribution of local anesthetics into the CSF following intranasal administration. Int J Pharm. 1998;168(2):137–45.CrossRefGoogle Scholar
  15. 15.
    Chow H-H, Chen Z, Matsuura GT. Direct transport of cocaine from the nasal cavity to the brain following intranasal cocaine administration in rats. J Pharm Sci. 1999;88(8):754–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Dahlin M, Jansson B, Bjork E. Levels of dopamine in blood and brain following nasal administration to rats. Eur J Pharm Sci. 2001;14(1):75–80.PubMedCrossRefGoogle Scholar
  17. 17.
    Fuseau E, Petricoul O, Moore KHP, Barrow A, Ibbotson T. Clinical pharmacokinetics of intranasal sumatriptan. Clin Pharmacokinet. 2002;41(11):801–11.PubMedCrossRefGoogle Scholar
  18. 18.
    Hussain A, Hirai S, Bawarshi R. Nasal absorption of propranolol from different dosage forms by rats and dogs. J Pharm Sci. 1980;69(12):1411–3.PubMedCrossRefGoogle Scholar
  19. 19.
    Turner JV, Maddalena DJ, Agatonovic-Kustrin S. Bioavailability prediction based on molecular structure for a diverse series of drugs. Pharm Res. 2004;21(1):68–82.PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2012

Authors and Affiliations

  • Hefei Zhang
    • 1
  • Chih-Wei Lin
    • 2
  • Maureen D. Donovan
    • 3
  1. 1.Oncology Clinical PharmacologyNovartis Pharmaceuticals CorporationFlorham ParkUSA
  2. 2.Clinical Pharmacology and PharmacometricsAbbott ParkUSA
  3. 3.Division of Pharmaceutics and Translational Therapeutics, College of PharmacyUniversity of IowaIowa CityUSA

Personalised recommendations