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Respiratory Function Assays in Safety Pharmacology

  • Dennis J. Murphy
Reference work entry

Abstract

The objectives of a safety pharmacology study of the respiratory system are to determine whether a drug has the potential to produce a change in respiratory function and to establish whether this change is a liability. Such changes can result from either the primary or secondary pharmacological properties of a drug or from organ dysfunction resulting from the toxicological properties of a drug.

Keywords

Inspiratory Flow Ventilatory Parameter Pleural Pressure Differential Pressure Transducer Sodium Cyanide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

I would like to thank Jonathan Renninger for his many technical and scientific contributions and Robert Coatney for his surgical contributions to the development of the respiratory models used in our laboratory.

References and Further Reading

  1. Amdur MO, Mead J (1958) Mechanics of respiration in unanesthetized guinea pigs. Am J Physiol 192:364–368PubMedGoogle Scholar
  2. Diamond L, O’Donnell M (1977) Pulmonary mechanics in normal rats. J Appl Physiol: Respir Environ Exercise Physiol 43:942–948Google Scholar
  3. Douglas JS, Dennis MW, Ridgeway P, Bouhuys A (1971) Airway dilation and constriction in spontaneously breathing guinea pigs. J Pharmacol Exp Ther 180:98–109Google Scholar
  4. Drorbaugh JE, Fenn WO (1955) A barometric method for measuring ventilation in newborn infants. Pediatrics 16:81–86PubMedGoogle Scholar
  5. Hamelmann E, Schwarze J, Takeda K, Oshiba A, Larsen GL, Irvin CG, Gelfand EW (1997) Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med 156:766–775PubMedGoogle Scholar
  6. Jacky JP (1980) Barometric measurement of tidal volume: effects of pattern and nasal temperature. J Appl Physiol: Respir Environ Exercise Physiol 49(2):319–325Google Scholar
  7. Kearney K, Metea M, Gleason T, Edwards T, Atterson P (2010) Evaluation of respiratory function in freely moving Beagle dogs using implanted impedance technology. J Pharmacol Toxicol Methods 62:119–126PubMedCrossRefGoogle Scholar
  8. Konno K, Mead J (1967) Measurement of the separate volume changes of the rib cage and abdomen during breathing. J Appl Physiol 22(3):407–422PubMedGoogle Scholar
  9. Lucke JN, Hall GM, Lister D (1976) Porcine malignant hyperthermia I: metabolic and physiologic changes. Brit J Anesthesiol 48:297–304CrossRefGoogle Scholar
  10. Lundblad LKA, Irvin CG, Adler A, Bates JHT (2002) A reevaluation of the validity of unrestrained plethysmography in mice. J Appl Physiol 93:1198–1207PubMedGoogle Scholar
  11. Martin JT, Perez W, Guenther SM, Lodato RF, Dantzker DR (1987) Does rib cage-abdominal paradox signify respiratory muscle fatigue? J Appl Physiol 63(2):851–860Google Scholar
  12. Mauderly JL (1974) The influence of sex and age on the pulmonary function of the beagle dog. J Gerontol 29:282–289PubMedCrossRefGoogle Scholar
  13. Murphy DJ, Jordan ME, Grande JC (1994) Microcapnometry: a non-invasive method for monitoring arterial CO2 tension in conscious rats. Toxicol Methods 4(3):177–187CrossRefGoogle Scholar
  14. Murphy DJ, Joran ME, Grando JC (1995) A non-invasive method for distinguishing central from peripheral nervous system effects of respiratory depressant drugs in conscious rats. Gen Pharmacol 26(3):569–575PubMedCrossRefGoogle Scholar
  15. Murphy DJ, Renninger JP, Gossett KA (1998) A novel method for chronic measurement of pleural pressure in conscious rats. J Pharmacol Toxicol Methods 39:137–141PubMedCrossRefGoogle Scholar
  16. Murphy DJ, Renninger JP, Coatney RW (2001) A novel method for chronic measurement of respiratory function in the conscious monkey. J Pharmacol Toxicol Methods 46:13–20PubMedCrossRefGoogle Scholar
  17. Murphy DJ, Renninger JP, Schramek D (2010) Respiratory inductive plethysmography as a method for measuring ventilator parameters in conscious, non-restrained dogs. J Pharmacol Toxicol Methods 62:47–53PubMedCrossRefGoogle Scholar
  18. Nuzzo PF, Anton WR (1986) Practical applications of capnography. Respir Ther 16:12–17Google Scholar
  19. O’Neil JJ, Raub JA (1984) Pulmonary function testing in small laboratory animals. Environ Health Perspect 56:11–22PubMedCrossRefGoogle Scholar
  20. Palecek F (1969) Measurement of ventilatory mechanics in the rat. J Appl Physiol 27:149–156PubMedGoogle Scholar
  21. Pennock BE, Cox CP, Rogers RM, Cain WA, Wells JH (1979) A noninvasive technique for measurement of changes in specific airway resistance. J Appl Physiol 46:39–406Google Scholar
  22. Sackner MA, Watson H, Belsito AS, Feinerman D, Suarez M, Gonzalez G, Bizousky F, Krieger B (1989) Calibration of respiratory inductive plethysmography during natural breathing. J Appl Physiol 66(1):410–420PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Safety PharmacologyGlaxoSmithKline PharmaceuticalsKing of PrussiaUSA

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