Inhaling medicines: delivering drugs to the body through the lungs

Key Points

  • The use of the lungs for the systemic delivery of medicines is virtually unexploited, and the ancient human practice of inhaling substances for systemic effect (with the exception of anaesthetic gases) has only just begun to be adopted by modern medicine.

  • Inhaled insulin for diabetics was recently approved in the US and Europe and is, so far, the only available inhaled protein-based drug for systemic effect.

  • The high surface area and high permeability of the lungs make them an ideal site for rapid systemic delivery of macromolecules and small-molecule drugs; however, the formulation of the drug is of crucial importance in 'getting the drug to the right place' for optimal absorption.

  • Small molecules are absorbed more rapidly through the lungs than through the gastrointestinal tract, with higher bioavailabilites and reduced first-pass metabolism by enzymes.

  • The lungs are significantly permeable to many peptides and proteins, with the rate of absorption decreasing with increasing molecular mass.

  • Here we review issues in the formulation of drugs that exploit the enormous gas-exchange surface of the lungs as an entry point into the systemic circulation.

Abstract

Remarkably, with the exception of anaesthetic gases, the ancient human practice of inhaling substances into the lungs for systemic effect has only just begun to be adopted by modern medicine. Treatment of asthma by inhaled drugs began in earnest in the 1950s, and now such 'topical' or targeted treatment with inhaled drugs is considered for treating many other lung diseases. More recently, major advances have led to increasing interest in systemic delivery of drugs by inhalation. Small molecules can be delivered with very rapid action, low metabolism and high bioavailability; and macromolecules can be delivered without injections, as highlighted by the recent approval of the first inhaled insulin product. Here, we review these advances, and discuss aspects of lung physiology and formulation composition that influence the systemic delivery of inhaled therapeutics.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Comparison of the lung epithelium at different sites within the lungs.
Figure 2: Factors that determine the deposition of inhaled particles.
Figure 3: The alveolocapillary permeability barrier.
Figure 4: The effect of particle size on the deposition of aerosol particles in the human respiratory tract following a slow inhalation and a 5-second breath hold.
Figure 5: Plasma concentration versus time curves following inhalation and injection, illustrating rapid pulmonary absorption.

References

  1. 1

    Patton, J. S., McCabe, J. G., Hansen, S. E. & Daugherty, A. L. Absorption of human growth hormone from the rat lung. Biotechnol. Ther. 1, 213–228 (l989–l990).

  2. 2

    Daugherty, A. L., Liggitt, H. D., McCabe, J. G., Moore, J. A. & Patton, J. S. Absorption of recombinant methionyl-human growth hormone (Met-hGH) from rat nasal mucosa. Int. J. Pharm. 45, 197–206 (l988).

  3. 3

    Moses, A. C., Gordon, G. S., Carey, M. C. & Flier, J. S. Insulin administered intranasally as an insulin-bile salt aerosol. Effectiveness and reproducibility in normal and diabetic subjects. Diabetes 32, 1040–1047 (l983).

  4. 4

    Salzman, R. et al. Intranasal aerosolized insulin. Mixed-meal studies and long term use in type 1 diabetes. N. Engl. J. Med. 312, 1078–1084 (1985).

    CAS  Article  Google Scholar 

  5. 5

    Patton, J. S., Bukar, J. & Nagarajan, S. Inhaled Insulin. Adv. Drug Del. Rev. 35, 235–247 (1999).

    CAS  Article  Google Scholar 

  6. 6

    Gänsslen, M. Uber inhalation von insulin. Klin. Wochenschr. 4, 71 (l925). First report of insulin absorption from the lung.

  7. 7

    Patton, J. S., Bukar, J. G. & Eldon, M. A. Clinical pharmacokinetics and pharmacodynamics of inhaled insulin. Clin. Pharmacokinet. 43, 781–801 (2004).

    CAS  Article  Google Scholar 

  8. 8

    Quattrin, T., Belanger, A., Bohannon, N. J. V. & Schwartz, S. L. Efficacy and safety of inhaled insulin (Exubera) compared with subcutaneous insulin therapy in patients with type 1 diabetes: results of a 6-month, randomized, comparative trial. Diabetes Care 27, 2622–2627 (2004).

    CAS  Article  Google Scholar 

  9. 9

    Hollander, P. A. et al. Efficacy and safety of inhaled insulin (Exubera) compared with subcutaneous insulin therapy in patients with type 2 diabetes: results of a 6-month, randomized, comparative trial. Diabetes Care 27, 2356–2362 (2004).

    CAS  Article  Google Scholar 

  10. 10

    DeFronzo, R. A. et al. Efficacy of inhaled insulin in patients with type 2 diabetes not controlled with diet and exercise: a 12-week, randomized, comparative trial. Diabetes Care 28, 1922–1928 (2005).

    CAS  Article  Google Scholar 

  11. 11

    Patton, J. S. Mechanisms of macromolecule absorption by the lungs. Adv. Drug Del. Rev. 19, 3–36 (l996).

  12. 12

    Patton, J. S. Fishburn, C. S. & Weers, J. G. The lungs as a portal of entry for systemic drug delivery. Proc. Am. Thorac. Soc. 1, 338–344 (2004). This report summarizes the large number of lung absorption studies by L. S. Shanker et al.

    CAS  Article  Google Scholar 

  13. 13

    Keith, I. M., Olson, E. B., Wilson, N. M. & Jefcoate, C. R. Immunological identification and effects of 3-methylcholanthrene and phenobarbital on rat pulmonary cytochrome P-450. Cancer Res. 47, 1878–1882 (1987).

    CAS  PubMed  Google Scholar 

  14. 14

    Ji, C. M. et al. Pulmonary cytochrome P-450 monooxygenase system and Clara cell differentiation in rats. Am. J. Physiol. 269, L393–L402 (1995).

    Google Scholar 

  15. 15

    Tronde, A. et al. Pulmonary absorption rate and bioavailability of drugs in vivo in rats: structure-absorption relationships and physicochemical profiling of drugs. J. Pharm. Sci. 92, 1216–1233 (2003).

    CAS  Article  Google Scholar 

  16. 16

    Weibel, E. R. Morphometry of the Human Lung (Academic, New York,1963).

    Google Scholar 

  17. 17

    Hogg, J. C. Response of the lung to inhaled particles. Med. J. Aust. 142, 675–678 (1985).

    CAS  PubMed  Google Scholar 

  18. 18

    Stone, K. C., Mercer, R. R., Gehr, P., Stockstill, B. & Crapo, J. D. Allometric relationships of cell numbers and size in the mammalian lung. Am. Respir. Cell Mol. Biol. 6, 235–243 (1992).

    CAS  Article  Google Scholar 

  19. 19

    Parra, S. C., Burnette, R., Preston Price, H. & Takaro, T. Zonal distribution of alveolar macrophages, type II pneumocytes, and alveolar septal connective tissue gaps in adult human lungs. Am. Rev. Respir. Dis. 133, 908–912 (1986).

    CAS  PubMed  Google Scholar 

  20. 20

    Lombry, C., Edwards, D. A., Preat, V. & Vanbever, R. Alveolar macrophages are a primary barrier to pulmonary absorption of macromolecules. Am. J. Physiol. Lung Cell Mol. Physiol. 286, L1002–L1008 (2004). Presents work detailing the significance of lung macrophages and their clearance of inhaled macromolecules, which will probably be expanded on a case-by-case basis, as new macromolecules are developed for aerosol delivery.

    CAS  Article  Google Scholar 

  21. 21

    Gorin, A. B. & Stewart, P. A. Differential permeability of endothelial and epithelial barriers to albumin flux. J. Appl. Physiol. Respir. Environ. Exercise Physiol. 47, 1315–1324 (l979).

  22. 22

    Wangensteen, O. D., Schneider, L. A., Fahrenkrug, S. C. Brottman, G. M. & Maynard, R. C. Tracheal epithelial permeability to nonelectrolytes: species differences. J. Appl. Physiol. 75, 1009–1018 (l993). One of the first publications to investigate solute flux in the airways mechanistically so that the relative contributions of diffusional and carrier-mediated transport could be explored.

  23. 23

    Bitonti, A. J. et al. Pulmonary delivery of an erythropoietin Fc fusion protein in non-human primates through an immunoglobulin transport pathway. Proc. Natl Acad. Sci. 101, 9763–9768 (2004).

    CAS  Article  Google Scholar 

  24. 24

    Low, S. C., Nunes, S. L., Bitonti, A. J. & Dumont, J. A. Oral and pulmonary delivery of FSH-Fc fusion proteins via neonatal Fc receptor-mediated transcytosis. Human Reprod. 20, 1805–1813 (2005).

    CAS  Article  Google Scholar 

  25. 25

    Codrons, V., Vanderbist, F., Ucakar, B., Preat, V. & Vanbever, R. Impact of formulation and methods of pulmonary delivery on absorption of parathyroid hormone (1–34) from rat lungs. J. Pharm. Sci. 93, 1241–1252 (2004).

    CAS  Article  Google Scholar 

  26. 26

    Adjei, L. A. & Carrigan, P. J. Pulmonary bioavailability of LH-RH analogs: some pharmaceutical guidelines. J. Biopharm. Sci. 3, 247–254 (l992).

  27. 27

    Boucher, R. C., Stutts, M. J. & Gatzy, J. T. Regional differences in bioelectric properties and ion flow in excised canine airways. J. Appl. Physiol. 51, 706–714 (1981).

    CAS  Article  Google Scholar 

  28. 28

    Byron, P. R. Drug delivery devices: issues in drug development. Proc. Am. Thorac. Soc. 1, 250–252 (2004).

    Article  Google Scholar 

  29. 29

    Byron, P. R. Prediction of drug residence times in regions of the human respiratory tract following aerosol inhalation. J. Pharm. Sci. 75, 433–438 (1986). The first quantitative theory defining drug and formulation properties capable of influencing aerosol drug absorption from, and duration in, the airways.

    CAS  Article  Google Scholar 

  30. 30

    Brown, R. A. & Schanker, L. S. Absorption of aerosolized drugs from the rat lung. Drug Metab. Dispos. 11, 355–360 (1983).

    CAS  PubMed  Google Scholar 

  31. 31

    Schanker, L. S. Mitchell, E. W. & Brown, R. A. Species comparison of drug absorption from the lung after aerosol inhalation or intratracheal injection. Drug Metab. Dispos. 14, 79–88 (1986).

    CAS  PubMed  Google Scholar 

  32. 32

    Byron, P. R. & Patton, J. S. Drug delivery via the respiratory tract. J. Aerosol Med. 7, 49–75 (1994).

    CAS  Article  Google Scholar 

  33. 33

    Effros, R. M. & Mason, G. R. Measurements of pulmonary epithelial permeability in vivo. Am Rev. Respir. Dis. 127, S59–S65 (1983).

    CAS  Article  Google Scholar 

  34. 34

    Enna, S. J & Schanker, L. S. Absorption of drugs from the rat lung. Am. J. Physiol. 223, 1227–1231 (1972). A pioneering study of drug absorption from pharmaceutical aerosols.

    CAS  Article  Google Scholar 

  35. 35

    Byron, P R. Determinants of drug and polypeptide bioavailability from aerosols delivered to the lung. Adv. Drug Deliv. Rev. 5, 107–132 (1990).

    CAS  Article  Google Scholar 

  36. 36

    Burch, S. G., Erbland, M. L., Gann, L. P. & Hiller, F. C. Plasma nicotine levels after inhalation of aerosolized nicotine. Am. Rev. Respir. Dis. 140, 955–957 (1989).

    CAS  Article  Google Scholar 

  37. 37

    Solvay Pharmaceuticals. Data show new synthetic Δ-9-THC inhaler offers safe, rapid delivery. Press release [online], (2005).

  38. 38

    Casella, J. et al. Novel inhalation technology delivers intravenous-like pharmacokinetics of prochlorperazine in healthy volunteers. Headache 45, S96 (2005).

    Article  Google Scholar 

  39. 39

    Rabinowitz, J. D. et al. Fast onset medications through thermally generated aerosols. J. Pharmacol. Exp. Therap. 309, 769 –775 (2004).

  40. 40

    Dershwitz, M. et al. Pharmacokinetics and pharmacodynamics of inhaled versus intravenous morphine in healthy volunteers. Anesthesiology 3, 619–628 (2000).

    Article  Google Scholar 

  41. 41

    Mather, L. E. et al. Pulmonary administration of aerosolized fentanyl: pharmacokinetic analysis of systemic delivery. Br. J. Clin. Pharmacol. 46, 37–43 (1998).

    CAS  Article  Google Scholar 

  42. 42

    Otulana, T. & Thipphawong, J. Systemic delivery of small molecules: product development issues focused on pain therapeutics. Respir. Drug Deliv. VIII 1, 97–104 (2002).

    Google Scholar 

  43. 43

    Wilson, D. M. et al. Physicochemical and pharmacological characterization of a Δ-9-THC aerosol generated by a metered dose inhaler. Drug Alcohol Depend. 67, 259–267, (2002).

    CAS  Article  Google Scholar 

  44. 44

    Davison, S. et al. Pharmacokinetics and acute safety of inhaled testosterone in postmenopausal women. J. Clin. Pharmacol. 45, 177–184 (2005).

    CAS  Article  Google Scholar 

  45. 45

    Byron, P. R. & Phillips, E. M. Absorption, clearance and dissolution in the lung. Respir. Drug Deliv. I, 107–141 (l999).

  46. 46

    Byron, P. R., Sun, Z. & Katayama, H. Solute absorption from the airways of the isolated rat lung V. Charge effects on the absorption of copolymers of N(2-hydroxyethyl)-DL-aspartamide with DL-aspartic acid or dimethylaminopropyl-DL-aspartamide. Pharm. Res. 16, 1104–1108 (1999).

    Article  Google Scholar 

  47. 47

    Patton, J. S., Nagarajan, S. & Clark, A. Pulmonary absorption and metabolism of peptides and proteins. Respiratory Drug Delivery VI I, 17–24 (l998).

  48. 48

    Heise, T. et al. The effect of insulin antibodies on the metabolic action of inhaled and subcutaneous insulin: a prospective randomized pharmacodynamic study. Diabetes Care 28, 2161–2169 (2005).

    CAS  Article  Google Scholar 

  49. 49

    Fineberg, S. E., Kawabata, T., Finco-Kent, D., Liu, C. & Krasner, A. Antibody response to inhaled insulin in patients with type 1 or type 2 diabetes. An analysis of initial phase II and III inhaled insulin (Exubera) trials and a two year extension trial. J. Clin. Endocrinol. Metab. 90, 3287–3294 (2005).

    CAS  Article  Google Scholar 

  50. 50

    Teeter, J. G. & Riese, R. J. Dissociation of lung function changes with humoral immunity during inhaled human insulin therapy. Am. J. Respir. Crit. Care Med. 173, 1194–200 (2006).

    CAS  Article  Google Scholar 

  51. 51

    Rosenstock, J., Cappelleri, J. C., Bolinder, B. & Gerber, R. A. Patient satisfaction and glycemic control after 1 year with inhaled insulin (Exubera) in patients with type 1 or type 2 diabetes. Diabetes Care 27, 1318–1323 (2004).

    Article  Google Scholar 

  52. 52

    Dumont, J. A. et al. Delivery of an erythropoietin–Fc fusion protein by inhalation in humans through an immunoglobulin transport pathway. J. Aerosol Med. 18, 294–303 (2005). Report of successful exploitation of a transporter to improve the pulmonary absorption of a biotech drug.

    CAS  Article  Google Scholar 

  53. 53

    Hogger, P. & Rohdewald, P. Glucocorticoid receptors and fluticasone propionate. Rev. Contemp. Pharmacotherap. 9, 501–522 (1998).

    CAS  Google Scholar 

  54. 54

    Johnson, M. Pharmacodynamics and pharmacokinetics of inhaled glucocorticoids. J. Allergy Clin. Immunol. 97, 169–176 (1996).

    CAS  Article  Google Scholar 

  55. 55

    Leach, C. L., Davidson, P. J., Hasselquist, B. E. & Boudreau R. J. . Lung deposition of hydrofluoroalkane-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone: a cross-over study in healthy volunteers. Chest 122, 510–516 (2002).

    CAS  Article  Google Scholar 

  56. 56

    Byron, P. R., Sakagami, M. & Rypacek, F. New pulmonary biopharmaceutics: Rate determining absorption and macromolecular transporters. Respir. Drug Deliv. VII 1, 41–48. (2000).

    Google Scholar 

  57. 57

    Esmailpour, N. et al. Distribution of inhaled fluticasone propionate between human lung tissue and serum in vivo. Eur. Respir. J. 10, 1496–1499 (1997). One of the few papers showing experimental evidence of extended lung retention of an inhaled low-solubility drug.

    CAS  Article  Google Scholar 

  58. 58

    Winkler, J., Hochhaus, G. & Derendorf, H. How the lung handles drugs: pharmacokinetics and pharmacodynamics of inhaled corticosteroids. Proc. Am. Thorac. Soc. 1, 356–363 (2004). Important concepts in pulmonary drug targeting are discussed.

    CAS  Article  Google Scholar 

  59. 59

    Thorsson, L., Edsbacker, S., Kalllen, A. & Lofdahl, C. G. Pharmacokinetics and systemic activity of fluticasone via Diskus and pMDI, and budesonide via turbuhaler. Br. J. Clin. Pharmacol. 52, 529–538 (2001).

    CAS  Article  Google Scholar 

  60. 60

    Brooks, A. D. et al. Inhaled aerosolization of all transretinoic acid for targeted pulmonary delivery. Cancer Chemother. Pharmacol. 46, 313–318 (2000).

    CAS  Article  Google Scholar 

  61. 61

    Beyer, J. et al. Use of amphotericin B aerosols for the prevention of pulmonary aspergillosis. Infection 22, 143–148 (1994).

    CAS  Article  Google Scholar 

  62. 62

    Miller-Larsson, A. Concluding clinical synergism from preclinical study data. Respir. Drug Deliv. IX 1, 87–98 (2004).

    Google Scholar 

  63. 63

    Kips, J. C. & Pauwels, R. A. Long acting inhaled β2-agonist therapy in asthma. Am. J. Respir. Crit. Care Med. 164, 923–932 (2001).

    CAS  Article  Google Scholar 

  64. 64

    Byron, P. R. Physicochemical effects on lung disposition of pharmaceutical aerosols. Aerosol Sci. Tech. 18, 223–229 (1993).

    CAS  Article  Google Scholar 

  65. 65

    Montgomery, A. B., Pitlick, W. H., Nardella, P., Tracewell, W. G. & Ramsey, B. W. Sputum concentrations and systemic pharmacokinetics of aerosolized tobramycin (Tobi) in diseased lungs. Respir. Drug Deliv. VII 1, 19–24 (2000).

    Google Scholar 

  66. 66

    Sakagami, M. & Byron, P. R. Respirable microspheres for inhalation: the potential of manipulating pulmonary disposition for improved therapeutic efficacy. Clin. Pharmacokinet. 44, 263–277 (2005).

    CAS  Article  Google Scholar 

  67. 67

    Doddoli, C. et al. In vitro and in vivo methotrexate disposition in alveolar macrophages: comparison of pharmacokinetic parameters of two formulations. Int. J. Pharm. 297, 180–189 (2005).

    CAS  Article  Google Scholar 

  68. 68

    Schreier, H. Pulmonary delivery of liposomal drugs. J. Liposome Res. 4, 229–238 (l994). An early review showing the importance of phospholipids as formulation additives — they can be used to engineer both prolonged retention and improved flow and dispersion of powders (also see reference 75).

  69. 69

    Zeng, M. X., Martin, G. P. & Marriott, C. Controlled delivery of drugs to the lung. Int. J. Pharm. 124, 149–164 (l995).

  70. 70

    Newhouse, M. T. et al. Inhalation of a dry powder tobramycin PulmoSphere formulation in healthy volunteers. Chest, 124, 360–366 (2003).

    CAS  Article  Google Scholar 

  71. 71

    Ramsey, B. W. et al. Efficacy of aerosolized tobramycin in patients with cystic fibrosis. N. Engl. J. Med. 328, 1740–1746 (l993).

  72. 72

    Newman, S. P. Agnew, J. E., Pavia, D. & Clarke, S. W. Inhaled aerosols: lung deposition and clinical applications. Clin. Phys. Physiol. Meas. 3, 1–20 (1982).

    CAS  Article  Google Scholar 

  73. 73

    Gonda, I. Aerosols for delivery of therapeutic and diagnostic agents to the respiratory tract. Crit. Rev. Ther. Drug Carrier Syst. 6, 273–313 (1990).

    CAS  PubMed  Google Scholar 

  74. 74

    Chono, S., Tanino, T., Seki, T. & Morimoto K. Influence of particle size on drug delivery to rat alveolar macrophages following pulmonary administration of ciprofloxacin incorporated into liposomes J. Drug Target. 14, 557–566 (2006).

    CAS  Article  Google Scholar 

  75. 75

    Edwards, D. A., Ben-Jebria A. & Langer, R. Recent advances in pulmonary drug delivery using large, porous inhaled particles. J. Appl. Physiol. 84, 379–385 (1998). The creation and use of geometrically large, but aerodynamically small minimally adhesive particle formulations might be a fundamental contribution to the development of new powder inhalers.

    Article  Google Scholar 

  76. 76

    Edwards, D. A. & Dunbar, C. Bioengineering of therapeutic aerosols. Annu. Rev. Biomed. Eng. 4, 93–107 (2002).

    CAS  Article  Google Scholar 

  77. 77

    Leach, C. L. et al. Modifying the pulmonary absorption and retention of proteins through PEGylation. Respir. Drug Deliv. IX 1, 69–78 (2004). Modifying proteins for inhalation by attachment of non-immunogenic hydrophilic materials might prove to be a means of extending airway duration without inducing adverse effects in the lung.

    Google Scholar 

  78. 78

    Niven, R. W., Whitcomb, K. L., Shaner, L., Ip, A. Y., & Kinstler, O. B. The pulmonary absorption of aerosolized and intratracheally instilled rhG-CSF and monoPEGylated rhG-CSF. Pharm. Res. 9, 1343–1349 (1995).

    Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to John S. Patton.

Ethics declarations

Competing interests

J. P. is a co-founder and Chief Scientific Officer of Nektar Therapeutics, a publicly traded company, specializing in pulmonary and PEGylation drug delivery technology.

Related links

Related links

DATABASES

Entrez Protein

hGH

insulin

FSH

EPO

OMIM

Type 1 diabetes

Type 2 diabetes

FURTHER INFORMATION

Nektar

Glossary

Bioavailability

The fraction or percentage of an administered drug or other substance that becomes available to the target tissue or blood after administration. Bioavailability is usually measured against an intravenous dose (absolute bioavailability) but can also be measured against other delivery routes such as subcutaneous injection (relative bioavailability).

Epithelium

A diverse group of tissues that covers or lines nearly all body surfaces, cavities and tubes that function as an interface between different biological compartments. Epithelial layers provide physical protection and containment, and also mediate organ-specific transport properties.

Mucociliary escalator

The self-cleansing system in the airways is composed of a moving epithelial raft of mucus secreted by goblet cells and propelled by ciliated cells. This system serves to move particles that are inhaled and deposited in the lungs up and out into the oesophagus, where material is coughed up and/or swallowed.

Macrophages

Pulmonary macrophages are scavenger cells in the lung derived from monocytes in the circulation. They help keep the lungs clean and although they have the capacity to produce many inflammatory mediators. Macrophages in the airways are relatively non-responsive to foreign materials when compared with other macrophages inside the body.

Transporters

Proteins embedded in plasma membranes of cells which facilitate the absorption of small or large molecules.

Tight junctions

The complex molecular apparatus that enables cell adhesion in epithelial and endothelial cell sheets. Tight junctions act as a mediator that retards the diffusion of solutes between cells and as a boundary between the apical and basal plasma-membrane domains.

Transcytosis

Transport through cell layers by movement directly through the cell cytoplasm (the transcellular pathway), perhaps via membrane vesicles called caveoli, in contrast to transport between cells via the tight junctions (the paracellular pathway).

Caveoli

The plasma membrane vesicles through which transcytosis can occur. These 'little caves' arise by invagination on one side of a cell and carry bound or engulfed material as a membrane vesicle or 'bubble' through the cell's cytoplasm to the other side of the cell. Here, the caveoli can fuse with the plasma membrane and release its cargo to the extracellular space.

Monodisperse particles

Aerosol particles that are all the same size. Most pharmaceutical aerosols are polydisperse. Their particle size is usually expressed as a median diameter surrounded by a spectrum of sizes.

Octanol–water partition coefficients

The equilibrium ratio of concentrations of drug molecules dissolved in an immiscible two-phase solvent system composed of water and octanol (high values reflect lipophilicity).

First-pass metabolism

Usually refers to oral drug administration where metabolism by enzymes in the gastrointestinal wall and liver reduce passage of intact drug into the systemic circulation. Significant amounts of a drug can be lost as it first passes into the body. Pulmonary metabolism of inhaled small-molecule drugs is usually very low compared with oral administration.

Excipients

A wide range of molecules that are used in pharmaceutical dosage forms to supply one or more of the following functions: add mass and flow properties, improve stability, mask or improve taste, improve injectability, reduce aggregation, improve dispersibility, prolong dissolution and so on.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Patton, J., Byron, P. Inhaling medicines: delivering drugs to the body through the lungs. Nat Rev Drug Discov 6, 67–74 (2007). https://doi.org/10.1038/nrd2153

Download citation

Further reading