Skip to main content
SpringerLink
Log in

Pharmacometrics in Pulmonary Diseases

  • Chapter
  • First Online:
Applied Pharmacometrics

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 14))

Abstract

Inhalation therapy has been successfully applied to treat respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD) with the primary goal of lung targeting, i.e., maximizing the beneficial local effects while keeping the systemic side effects to a minimum. However, inhalation drug delivery remains challenging because of the plethora of factors that can impact the fate of an inhaled drug. These factors can be related to (1) anatomy/physiology of the lung (e.g., differences in the cellular profile and the anatomical features between the central and the peripheral lung; mucociliary escalator in the central lung region), (2) physicochemical properties of the drug (influence of particle size distribution on the degree and site of lung deposition; particle dissolution rate), and (3) patient characteristics (differences in breathing patterns and airway caliber between a healthy and a diseased lung, and its impact on the variability between and within subjects). Hence, it is imperative to incorporate the impact of these factors while developing models to accurately predict the pulmonary and systemic side effects and optimize inhalation therapy. PK/PD models describing the factors important for enhancing the benefit to risk ratio, models quantifying the systemic side effects of inhalation therapy, mechanistic/physiological PK models accurately predicting the systemic PK of inhalation drugs, and focusing on corticosteroids and β-2 agonists are described in this chapter.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abo T, Kawate T, Itoh K, Kumagai K (1981) Studies on the bioperiodicity of the immune response. I. Circadian rhythms of human T, B, and K cell traffic in the peripheral blood. J Immunol 126:1360–1363

    CAS  PubMed  Google Scholar 

  • Agoram B, Woltosz WS, Bolger MB (2001) Predicting the impact of physiological and biochemical processes on oral drug bioavailability. Adv Drug Deliv Rev 50(Suppl 1):S41–S67

    Article  CAS  PubMed  Google Scholar 

  • Ahmed SF, Tucker P, Mushtaq T et al (2002) Short-term effects on linear growth and bone turnover in children randomized to receive prednisolone or dexamethasone. Clin Endocrinol (Oxf) 57:185–191

    Article  CAS  Google Scholar 

  • Ariens EJ (1954) Affinity and intrinsic activity in the theory of competitive inhibition. I. Problems and theory. Arch Int Pharmacodyn Thér 99:32–49

    CAS  PubMed  Google Scholar 

  • Bates DV, Fish BR, Hatch TF et al (1966) Deposition and retention models for internal dosimetry of the human respiratory tract. Task group on lung dynamics. Health Phys 12:173–207

    CAS  PubMed  Google Scholar 

  • Beato M, Kalimi M, Feigelson P (1972) Correlation between glucocorticoid binding to specific liver cytosol receptors and enzyme induction in vivo. Biochem Biophys Res Commun 47:1464–1472

    Article  CAS  PubMed  Google Scholar 

  • Borghardt J, Weber B, Staab A et al (2014) Exapnding the mechanistic knowledge about pulmonary absorption processes using a population pharmacokinetic model for inhaled olodaterol. Respir Drug Deliv 2:417–422

    Google Scholar 

  • Borgström L, Bondesson E, Morén F et al (1994) Lung deposition of budesonide inhaled via Turbuhaler: a comparison with terbutaline sulphate in normal subjects. Eur Respir J 7:69–73

    Article  PubMed  Google Scholar 

  • Bot AI, Tarara TE, Smith DJ et al (2000) Novel lipid-based hollow-porous microparticles as a platform for immunoglobulin delivery to the respiratory tract. Pharm Res 17:275–283

    Article  CAS  PubMed  Google Scholar 

  • Brown RA, Schanker LS (1983) Absorption of aerosolized drugs from the rat lung. Drug Metab Dispos 11:355–360

    CAS  PubMed  Google Scholar 

  • Byron PR (1986) Prediction of drug residence times in regions of the human respiratory tract following aerosol inhalation. J Pharm Sci 75:433–438

    Article  CAS  PubMed  Google Scholar 

  • Carroll N, Cooke C, James A (1997) The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics. Eur Respir J 10:292–300

    Article  CAS  PubMed  Google Scholar 

  • Carstairs JR, Nimmo AJ, Barnes PJ (1985) Autoradiographic visualization of beta-adrenoceptor subtypes in human lung. Am Rev Respir Dis 132:541–547

    CAS  PubMed  Google Scholar 

  • Chakraborty A, Krzyzanski W, Jusko WJ (1999) Mathematical modeling of circadian cortisol concentrations using indirect response models: comparison of several methods. J Pharmacokinet Biopharm 27:23–43

    Article  CAS  PubMed  Google Scholar 

  • Chaudhuri SR, Lukacova V (2010) Simulating delivery of pulmonary (and intranasal) aerosolised drugs, pp 26–30. ONdrugDelivery. http://www.ondrugdelivery.com/publications/OINDP%20November%202010/OINDP%20November%202010%20lo%20res.pdf. Accessed 26 Sept 2013

  • Chrousos GP, Harris AG (1998) Hypothalamic–pituitary–adrenal axis suppression and inhaled corticosteroid therapy. 2. Review of the literature. Neuroimmunomodulation 5:288–308

    Article  CAS  PubMed  Google Scholar 

  • Dahlberg E, Thalén A, Brattsand R et al (1984) Correlation between chemical structure, receptor binding, and biological activity of some novel, highly active, 16 alpha, 17 alpha-acetal-substituted glucocorticoids. Mol Pharmacol 25:70–78

    CAS  PubMed  Google Scholar 

  • Daley-Yates PT, Richards DH (2004) Relationship between systemic corticosteroid exposure and growth velocity: development and validation of a pharmacokinetic/pharmacodynamic model. Clin Ther 26:1905–1919

    Article  CAS  PubMed  Google Scholar 

  • Daley-Yates PT, Price AC, Sisson JR et al (2001) Beclomethasone dipropionate: absolute bioavailability, pharmacokinetics and metabolism following intravenous, oral, intranasal and inhaled administration in man. Br J Clin Pharmacol 51:400–409

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Davies CN (1982) Deposition of particles in the human lungs as a function of particle size and breathing pattern: an empirical model. Ann Occup Hyg 26:119–135

    Article  CAS  PubMed  Google Scholar 

  • DeHaan WH, Finlay WH (2001) In vitro monodisperse aerosol deposition in a mouth and throat with six different inhalation devices. J Aerosol Med 14:361–367

    Article  CAS  PubMed  Google Scholar 

  • Dellamary LA, Tarara TE, Smith DJ et al (2000) Hollow porous particles in metered dose inhalers. Pharm Res 17:168–174

    Article  CAS  PubMed  Google Scholar 

  • Derendorf H, Hochhaus G, Rohatagi S et al (1995) Pharmacokinetics of triamcinolone acetonide after intravenous, oral, and inhaled administration. J Clin Pharmacol 35:302–305

    Article  CAS  PubMed  Google Scholar 

  • Dinh KV, Myers DJ, Noymer PD, Cassella JV (2010) In vitro aerosol deposition in the oropharyngeal region for Staccato loxapine. J Aerosol Med Pulm Drug Deliv 23:253–260. doi:10.1089/jamp.2009.0814

    Article  CAS  PubMed  Google Scholar 

  • Druzgala P, Hochhaus G, Bodor N (1991) Soft drugs—10. Blanching activity and receptor binding affinity of a new type of glucocorticoid: loteprednol etabonate. J Steroid Biochem Mol Biol 38:149–154

    Article  CAS  PubMed  Google Scholar 

  • Earp JC, Dubois DC, Molano DS et al (2008a) Modeling corticosteroid effects in a rat model of rheumatoid arthritis I: mechanistic disease progression model for the time course of collagen-induced arthritis in Lewis rats. J Pharmacol Exp Ther 326:532–545. doi:10.1124/jpet.108.137372

    Google Scholar 

  • Earp JC, Dubois DC, Molano DS et al (2008b) Modeling corticosteroid effects in a rat model of rheumatoid arthritis II: mechanistic pharmacodynamic model for dexamethasone effects in Lewis rats with collagen-induced arthritis. J Pharmacol Exp Ther 326:546–554. doi:10.1124/jpet.108.137414

    Google Scholar 

  • Edsbäcker S, Brattsand R (2002) Budesonide fatty-acid esterification: a novel mechanism prolonging binding to airway tissue. Review of available data. Ann Allergy Asthma Immunol 88:609–616. doi:10.1016/S1081-1206(10)61893-5

    Article  PubMed  Google Scholar 

  • Edwards DA, Hanes J, Caponetti G et al (1997) Large porous particles for pulmonary drug delivery. Science 276:1868–1871

    Article  CAS  PubMed  Google Scholar 

  • Fuglsang G, Pedersen S, Borgström L (1989) Dose–response relationships of intravenously administered terbutaline in children with asthma. J Pediatr 114:315–320

    Article  CAS  PubMed  Google Scholar 

  • Geller DE, Weers J, Heuerding S (2011) Development of an inhaled dry-powder formulation of tobramycin using PulmoSphereTM technology. J Aerosol Med Pulm Drug Deliv 24:175–182. doi:10.1089/jamp.2010.0855

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gobburu JVS, Lesko LJ (2009) Quantitative disease, drug, and trial models. Annu Rev Pharmacol Toxicol 49:291–301. doi:10.1146/annurev.pharmtox.011008.145613

    Article  CAS  PubMed  Google Scholar 

  • Gonda I (1988) Drugs administered directly into the respiratory tract: modeling of the duration of effective drug levels. J Pharm Sci 77:340–346

    Article  CAS  PubMed  Google Scholar 

  • Gonda I (2004) Targeting by deposition. In: Hickey AJ (ed) Pharmaceutical inhalation aerosol technology, 2nd edn. Merckel Dekker, New York, pp 65–88

    Google Scholar 

  • Green SA, Spasoff AP, Coleman RA et al (1996) Sustained activation of a G protein-coupled receptor via “anchored” agonist binding. Molecular localization of the salmeterol exosite within the 2-adrenergic receptor. J Biol Chem 271:24029–24035

    Article  CAS  PubMed  Google Scholar 

  • Hardy JG, Chadwick TS (2000) Sustained release drug delivery to the lungs: an option for the future. Clin Pharmacokinet 39:1–4. doi:10.2165/00003088-200039010-00001

    Article  CAS  PubMed  Google Scholar 

  • Harrison TW, Tattersfield AE (2003) Plasma concentrations of fluticasone propionate and budesonide following inhalation from dry powder inhalers by healthy and asthmatic subjects. Thorax 58:258–260

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hickey A, Thompson D (2004) Physiology of the airways. In: Hickey AJ (ed) Pharmaceutical inhalation aerosol technology, 2nd edn. Marcel Dekker, New York, pp 1–29

    Google Scholar 

  • Hindle M, Longest PW (2010) Evaluation of enhanced condensational growth (ECG) for controlled respiratory drug delivery in a mouth–throat and upper tracheobronchial model. Pharm Res 27:1800–1811. doi:10.1007/s11095-010-0165-z

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hindle M, Longest PW (2012) Condensational growth of combination drug-excipient submicrometer particles for targeted high-efficiency pulmonary delivery: evaluation of formulation and delivery device. J Pharm Pharmacol 64:1254–1263. doi:10.1111/j.2042-7158.2012.01476.x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hochhaus G, Möllmann H (1992) Pharmacokinetic/pharmacodynamic characteristics of the beta-2-agonists terbutaline, salbutamol and fenoterol. Int J Clin Pharmacol Ther Toxicol 30:342–362

    CAS  PubMed  Google Scholar 

  • Hochhaus G, Chen LS, Ratka A et al (1992a) Pharmacokinetic characterization and tissue distribution of the new glucocorticoid soft drug loteprednol etabonate in rats and dogs. J Pharm Sci 81:1210–1215

    Google Scholar 

  • Hochhaus G, Schmidt EW, Rominger KL, Möllmann H (1992b) Pharmacokinetic/dynamic correlation of pulmonary and cardiac effects of fenoterol in asthmatic patients after different routes of administration. Pharm Res 9:291–297

    Google Scholar 

  • Hochhaus G, Möllmann H, Derendorf H, Gonzalez-Rothi RJ (1997) Pharmacokinetic/pharmacodynamic aspects of aerosol therapy using glucocorticoids as a model. J Clin Pharmacol 37:881–892

    Article  CAS  PubMed  Google Scholar 

  • Hong Y, Mager DE, Blum RA, Jusko WJ (2007) Population pharmacokinetic/pharmacodynamic modeling of systemic corticosteroid inhibition of whole blood lymphocytes: modeling interoccasion pharmacodynamic variability. Pharm Res 24:1088–1097. doi:10.1007/s11095-006-9232-x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Issar M, Mobley C, Khan P, Hochhaus G (2004) Pharmacokinetics and pharmacodynamics of drugs delivered to the lungs. In: Hickey A (ed) Pharmaceutical inhalation aerosol technology, 2nd edn. Marcel Dekker, New York, pp 215–252

    Google Scholar 

  • Iyengar R, Zhao S, Chung S-W et al (2012) Merging systems biology with pharmacodynamics. Sci Transl Med 4:126ps7. doi:10.1126/scitranslmed.3003563

    Article  PubMed Central  PubMed  Google Scholar 

  • Jeffery PK (1987) The origins of secretions in the lower respiratory tract. Eur J Respir Dis Suppl 153:34–42

    CAS  PubMed  Google Scholar 

  • Jones HM, Dickins M, Youdim K et al (2012) Application of PBPK modelling in drug discovery and development at Pfizer. Xenobiotica 42:94–106. doi:10.3109/00498254.2011.627477

    Article  CAS  PubMed  Google Scholar 

  • Jonkers R, van Boxtel CJ, Koopmans RP, Oosterhuis B (1989) A nonsteady-state agonist antagonist interaction model using plasma potassium concentrations to quantify the beta-2 selectivity of beta blockers. J Pharmacol Exp Ther 249:297–302

    CAS  PubMed  Google Scholar 

  • Jusko WJ (2013) Moving from basic toward systems pharmacodynamic models. J Pharm Sci 102:2930–2940. doi:10.1002/jps.23590

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Koopmans RP, Braat MC, Oosterhuis B, van Boxtel CJ (1992) Time-dependent effects of dexamethasone administration on the suppression of plasma hydrocortisone, assessed with a pharmacokinetic model. J Pharmacol Exp Ther 262:503–508

    CAS  PubMed  Google Scholar 

  • Kraft M, Djukanovic R, Wilson S et al (1996) Alveolar tissue inflammation in asthma. Am J Respir Crit Care Med 154:1505–1510. doi:10.1164/ajrccm.154.5.8912772

    Article  CAS  PubMed  Google Scholar 

  • Labiris NR, Dolovich MB (2003) Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol 56:588–599

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lee JY, Garnett CE, Gobburu JVS et al (2011) Impact of pharmacometric analyses on new drug approval and labelling decisions: a review of 198 submissions between 2000 and 2008. Clin Pharmacokinet 50:627–635. doi:10.2165/11593210-000000000-00000

    Article  PubMed  Google Scholar 

  • Lesko LJ, Rowland M, Peck CC, Blaschke TF (2000) Optimizing the science of drug development: opportunities for better candidate selection and accelerated evaluation in humans. Pharm Res 17:1335–1344

    Article  CAS  PubMed  Google Scholar 

  • Lipworth BJ, Jackson CM (2000) Safety of inhaled and intranasal corticosteroids: lessons for the new millennium. Drug Saf 23:11–33

    Article  CAS  PubMed  Google Scholar 

  • Longest PW, McLeskey JT, Hindle M (2010) Characterization of nanoaerosol size change during enhanced condensational growth. Aerosol Sci Technol 44:473–483. doi:10.1080/02786821003749525

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Longest PW, Tian G, Walenga RL, Hindle M (2012) Comparing MDI and DPI aerosol deposition using in vitro experiments and a new stochastic individual path (SIP) model of the conducting airways. Pharm Res 29:1670–1688. doi:10.1007/s11095-012-0691-y

    Article  CAS  PubMed  Google Scholar 

  • Lönnebo A, Grahnén A, Karlsson MO (2007) An integrated model for the effect of budesonide on ACTH and cortisol in healthy volunteers. Br J Clin Pharmacol 64:125–132. doi:10.1111/j.1365-2125.2007.02867.x

    Article  PubMed Central  PubMed  Google Scholar 

  • Lukacova V, Ray Chaudhuri S, Miller N et al (2010) Simulation of tobramycin pharmacokinetics after pulmonary administration. 37th Annual Meeting & Exposition Controlled Release Society. 37th Annual Meeting and Exposition of the Controlled Release Society, Portland, OR. July 10–14, 2010.

    Google Scholar 

  • Mackie AE, Ventresca GP, Fuller RW, Bye A (1996) Pharmacokinetics of intravenous fluticasone propionate in healthy subjects. Br J Clin Pharmacol 41:539–542

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Martonen TB, Katz IM (1993) Deposition patterns of aerosolized drugs within human lungs: effects of ventilatory parameters. Pharm Res 10:871–878

    Article  CAS  PubMed  Google Scholar 

  • Meibohm B, Derendorf H, Möllmann H et al (1999) Mechanism-based PK/PD model for the lymphocytopenia induced by endogenous and exogenous corticosteroids. Int J Clin Pharmacol Ther 37:367–376

    CAS  PubMed  Google Scholar 

  • Milad MA, Ludwig EA, Lew KH et al (1994) The pharmacokinetics and pharmacodynamics of Methylprednisolone in chronic renal failure. Am J Ther 1:49–57

    Article  PubMed  Google Scholar 

  • Miller N, Ray Chaudhuri S, Lukacova V et al (2010) Development of physiologically-based pharmacokinetic (PBPK) model for predicting deposition and disposition following inhaled and intranasal administration. Respir Drug Deliv 2:579–584

    Google Scholar 

  • Miller-Larsson A, Mattsson H, Hjertberg E et al (1998) Reversible fatty acid conjugation of budesonide. Novel mechanism for prolonged retention of topically applied steroid in airway tissue. Drug Metab Dispos 26:623–630

    CAS  PubMed  Google Scholar 

  • Miyawaki T, Taga K, Nagaoki T et al (1984) Circadian changes of T lymphocyte subsets in human peripheral blood. Clin Exp Immunol 55:618–622

    CAS  PubMed Central  PubMed  Google Scholar 

  • Möllmann H, Wagner M, Meibohm B et al (1998) Pharmacokinetic and pharmacodynamic evaluation of fluticasone propionate after inhaled administration. Eur J Clin Pharmacol 53:459–467

    Article  PubMed  Google Scholar 

  • Nagaraja NV, Pechstein B, Erb K et al (2003) Pharmacokinetic/pharmacodynamic modeling of luteinizing hormone (LH) suppression and LH surge delay by cetrorelix after single and multiple doses in healthy premenopausal women. J Clin Pharmacol 43:243–251

    Article  CAS  PubMed  Google Scholar 

  • Nave R, Meyer W, Fuhst R, Zech K (2005) Formation of fatty acid conjugates of ciclesonide active metabolite in the rat lung after 4-week inhalation of ciclesonide. Pulm Pharmacol Ther 18:390–396. doi:10.1016/j.pupt.2005.02.012

    Article  CAS  PubMed  Google Scholar 

  • Nave R, Fisher R, Zech K (2006) In vitro metabolism of ciclesonide in human lung and liver precision-cut tissue slices. Biopharm Drug Dispos 27:197–207. doi:10.1002/bdd.500

    Article  CAS  PubMed  Google Scholar 

  • Newman SP, Clark AR, Talaee N, Clarke SW (1989) Pressurised aerosol deposition in the human lung with and without an “open” spacer device. Thorax 44:706–710

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Newman SP, Brown J, Steed KP et al (1998) Lung deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicines: comparison of RESPIMAT with conventional metered-dose inhalers with and without spacer devices. Chest 113:957–963

    Article  CAS  PubMed  Google Scholar 

  • Newman S, Salmon A, Nave R, Drollmann A (2006) High lung deposition of 99mTc-labeled ciclesonide administered via HFA-MDI to patients with asthma. Respir Med 100:375–384. doi:10.1016/j.rmed.2005.09.027

    Article  PubMed  Google Scholar 

  • Nikander K, Prince I, Coughlin S et al (2010) Mode of breathing-tidal or slow and deep-through the I-neb Adaptive Aerosol Delivery (AAD) system affects lung deposition of (99m)Tc-DTPA. J Aerosol Med Pulm Drug Deliv 23(Suppl 1):S37–S43. doi:10.1089/jamp.2009.0786

    CAS  PubMed  Google Scholar 

  • Oneda K (1999) Dexamethasone-induced apoptosis in peripheral T lymphocytes from patients with asthma. Arerugi 48:13–22

    CAS  PubMed  Google Scholar 

  • Palm S, Postler E, Hinrichsen H et al (1996) Twenty-four-hour analysis of lymphocyte subpopulations and cytokines in healthy subjects. Chronobiol Int 13:423–434

    Article  CAS  PubMed  Google Scholar 

  • Peet CF, Enos T, Nave R et al (2005) Identification of enzymes involved in phase I metabolism of ciclesonide by human liver microsomes. Eur J Drug Metab Pharmacokinet 30:275–286

    Article  CAS  PubMed  Google Scholar 

  • Petruzzelli S, De Flora S, Bagnasco M et al (1989) Carcinogen metabolism studies in human bronchial and lung parenchymal tissues. Am Rev Respir Dis 140:417–422. doi:10.1164/ajrccm/140.2.417

    Article  CAS  PubMed  Google Scholar 

  • Pitcairn G, Reader S, Pavia D, Newman S (2005) Deposition of corticosteroid aerosol in the human lung by Respimat Soft Mist inhaler compared to deposition by metered dose inhaler or by Turbuhaler dry powder inhaler. J Aerosol Med 18:264–272. doi:10.1089/jam.2005.18.264

    Article  CAS  PubMed  Google Scholar 

  • Rohatagi S, Hochhaus G, Mollmann H et al (1995) Pharmacokinetic and pharmacodynamic evaluation of triamcinolone acetonide after intravenous, oral, and inhaled administration. J Clin Pharmacol 35:1187–1193

    Article  CAS  PubMed  Google Scholar 

  • Rohatagi S, Bye A, Mackie AE, Derendorf H (1996a) Mathematical modeling of cortisol circadian rhythm and cortisol suppression. Eur J Pharm Sci 4:341–350

    Google Scholar 

  • Rohatagi S, Täuber U, Richter K, Derendorf H (1996b) Pharmacokinetic/pharmacodynamic modeling of cortisol suppression after oral administration of fluocortolone. J Clin Pharmacol 36:311–314

    Google Scholar 

  • Rohatagi S, Arya V, Zech K et al (2003) Population pharmacokinetics and pharmacodynamics of ciclesonide. J Clin Pharmacol 43:365–378

    Article  CAS  PubMed  Google Scholar 

  • Rohatagi S, Luo Y, Shen L et al (2005) Protein binding and its potential for eliciting minimal systemic side effects with a novel inhaled corticosteroid, ciclesonide. Am J Ther 12:201–209

    Article  PubMed  Google Scholar 

  • Ryrfeldt A, Andersson P, Edsbäcker S et al (1982) Pharmacokinetics and metabolism of budesonide, a selective glucocorticoid. Eur J Respir Dis Suppl 122:86–95

    CAS  PubMed  Google Scholar 

  • Schanker LS, Mitchell EW, Brown RA (1986) Species comparison of drug absorption from the lung after aerosol inhalation or intratracheal injection. Drug Metab Dispos 14:79–88

    CAS  PubMed  Google Scholar 

  • Singh SD, Whale C, Houghton N et al (2003) Pharmacokinetics and systemic effects of inhaled fluticasone propionate in chronic obstructive pulmonary disease. Br J Clin Pharmacol 55:375–381

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Slayter KL, Ludwig EA, Lew KH et al (1996) Oral contraceptive effects on methylprednisolone pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 59:312–321. doi:10.1016/S0009-9236(96)80009-9

    Article  CAS  PubMed  Google Scholar 

  • Smith H (1995) Human respiratory tract model for radiological protection. ICRP Publication (1994) 66. Ann. ICRP 24:1–3

    Google Scholar 

  • Stark JG, Werner S, Homrighausen S et al (2006) Pharmacokinetic/pharmacodynamic modeling of total lymphocytes and selected subtypes after oral budesonide. J Pharmacokinet Pharmacodyn 33:441–459. doi:10.1007/s10928-006-9013-5

    Article  CAS  PubMed  Google Scholar 

  • Stuart BO (1984) Deposition and clearance of inhaled particles. Environ Health Perspect 55:369–390

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Suarez S, Gonzalez-Rothi RJ, Schreier H, Hochhaus G (1998) Effect of dose and release rate on pulmonary targeting of liposomal triamcinolone acetonide phosphate. Pharm Res 15:461–465

    Article  CAS  PubMed  Google Scholar 

  • Suntres ZE, Shek PN (1998) Liposomes promote pulmonary glucocorticoid delivery. J Drug Target 6:175–182. doi:10.3109/10611869808997891

    Article  CAS  PubMed  Google Scholar 

  • Thiel CG (1998) Can in vitro particle size measurements be used to predict pulmonary deposition of aerosol from inhalers? J Aerosol Med 11(Suppl 1):S43–S52

    PubMed  Google Scholar 

  • Tian G, Longest PW, Li X, Hindle M (2013) Targeting aerosol deposition to and within the lung airways using excipient enhanced growth. J Aerosol Med Pulm Drug Deliv 26:248–265. doi:10.1089/jamp.2012.0997

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tunek A, Sjödin K, Hallström G (1997) Reversible formation of fatty acid esters of budesonide, an antiasthma glucocorticoid, in human lung and liver microsomes. Drug Metab Dispos 25:1311–1317

    CAS  PubMed  Google Scholar 

  • Tyler WS (1983) Comparative subgross anatomy of lungs. Pleuras, interlobular septa, and distal airways. Am Rev Respir Dis 128:S32–S36

    Google Scholar 

  • Usmani OS, Biddiscombe MF, Barnes PJ (2005) Regional lung deposition and bronchodilator response as a function of beta2-agonist particle size. Am J Respir Crit Care Med 172:1497–1504. doi:10.1164/rccm.200410-1414OC

    Article  PubMed  Google Scholar 

  • Van Gossum A, Schmit A, Peny MO (1998) Oral budesonide for lymphocytic colitis. Am J Gastroenterol 93:270. doi:10.1111/j.1572-0241.1998.270_1.x

    Article  CAS  PubMed  Google Scholar 

  • Vodovotz Y, An G (2010) Systems biology and inflammation. Methods Mol Biol 662:181–201. doi:10.1007/978-1-60761-800-3_9

    Article  CAS  PubMed  Google Scholar 

  • Wald JA, Law RM, Ludwig EA et al (1992) Evaluation of dose-related pharmacokinetics and pharmacodynamics of prednisolone in man. J Pharmacokinet Biopharm 20:567–589

    Article  CAS  PubMed  Google Scholar 

  • Weber B, Hochhaus G (2013) A pharmacokinetic simulation tool for inhaled corticosteroids. AAPS J 15:159–171. doi:10.1208/s12248-012-9420-z

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Weda M, Zanen P, de Boer AH et al (2008) The therapeutic index of locally acting inhaled drugs as a function of their fine particle mass and particle size distribution: a literature review. Curr Drug Deliv 5:142–147

    Article  CAS  PubMed  Google Scholar 

  • Weibel E (1963) Morphometry of the human lung, 1st edn. Springer, New York

    Book  Google Scholar 

  • Winkler J, Hochhaus G, Derendorf H (2004) How the lung handles drugs: pharmacokinetics and pharmacodynamics of inhaled corticosteroids. Proc Am Thorac Soc 1:356–363. doi:10.1513/pats.200403-025MS

    Article  CAS  PubMed  Google Scholar 

  • Xu J, Nave R, Lahu G et al (2010) Population pharmacokinetics and pharmacodynamics of inhaled ciclesonide and fluticasone propionate in patients with persistent asthma. J Clin Pharmacol 50:1118–1127. doi:10.1177/0091270009354994

    Article  CAS  PubMed  Google Scholar 

  • Zhao P, Zhang L, Grillo JA et al (2011) Applications of physiologically based pharmacokinetic (PBPK) modeling and simulation during regulatory review. Clin Pharmacol Ther 89:259–267. doi:10.1038/clpt.2010.298

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Pharmacy, University of Florida, 1345 Center Drive, P3-20 JHMHC, 32610-0494, Gainesville, FL, USA

    Bhargava Kandala PhD & Günther Hochhaus PhD

Authors
  1. Bhargava Kandala PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Günther Hochhaus PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Günther Hochhaus PhD .

Editor information

Editors and Affiliations

  1. University of Florida, Department of Pharmaceutics, Center for Pharmacometrics & Systems Pharmacology, Orlando, Florida, USA

    Stephan Schmidt

  2. University of Florida, College of Pharmacy, Department of Pharmaceutics, Gainesville, Florida, USA

    Hartmut Derendorf

Appendices

Appendices

Appendix 1

figure a

Appendix 2

figure b

Appendix 3

figure c

Rights and permissions

Reprints and permissions

Copyright information

© 2014 American Association of Pharmaceutical Scientists

About this chapter

Cite this chapter

Kandala, B., Hochhaus, G. (2014). Pharmacometrics in Pulmonary Diseases. In: Schmidt, S., Derendorf, H. (eds) Applied Pharmacometrics. AAPS Advances in the Pharmaceutical Sciences Series, vol 14. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1304-6_12

Download citation

Publish with us

Policies and ethics

Search

Navigation