Pharmacokinetics of inhalants

The ventilated and perfused human lung lobe was used as described by Linder and co-workers [74], A twofold difference in the appearance of drug and metabolites in the perfusate was found for the two formulations. Small fractions of the applied dose of BDP were immediately detectable in the perfusate and the amount of the major metabolite, beclomethasone-17-propionate (17-BMP), increased over the experimental period. These observations were similar to the clinical observations that BDP is detected rapidly in the plasma after inhalation and that the appearance of the active metabolite 17-BMP occurs rapidly. The kinetic differences between the formulations were explained on the basis of particle size effects with the conclusion that the discriminatory value of this system to examine the lung pharmacokinetics of inhaled medicines in the absence of systemic effects such as hepatic metabolism was apparent. 

Lipworth BJ (1996) Pharmacokinetics of inhaled drugs. Br J Clin Pharmacol 42 697-705. 

Absorption, Distribution, Metabolism, and Excretion. Data are available on the pharmacokinetics of hexachlorobutadiene in animals by the oral route, but not in humans. There are no data in humans or animals on exposures to hexachlorobutadiene by the inhalation or dermal routes. Because of the key role of the liver in producing the metabolites which are responsible for the nephrotoxicity of this compound, knowledge of the pharmacokinetics of inhalation and dermal exposures would be valuable. Oral studies reported the presence of the enzymes responsible for the glutathione conjugation reaction and the subsequent formation of derivatives in the liver, intestines, and kidney. 

McKenna, M.J., Zempel, J.A. Braun, WH. (1982) The pharmacokinetics of inhaled methylene chloride in rats. Toxicol, appl. Pharmacol., 65, 1-10... 

Nolan, R.J., Unger, S.M. Muller, C.J. (1982) Pharmacokinetics of inhaled [ C]-2-nitropropane in male Sprague-Dawley rats. Ecotoxicol. environ. Saf, 6, 388-397... 

Sullivan TM, Born GS, Carlson GP, et al. 1983. The pharmacokinetics of inhaled chlorobenzene in the rat. Toxicol Appl Pharmacol 71 194-203. 

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

M. Hill, Effect of delivery mode on pharmacokinetics of inhaled drugs Experience with beclomethasone, Respiratory Drug Delivery VI. (R. Dalby, P. Byron, and S. J. Farr, eds.), Interpharm Press, Englewood, CO, 1998, p. 53. 

Otulana, B., Okikawa, J., Linn, L., Morishige, R., and Thipphawong, J. (2004), Safety and pharmacokinetics of inhaled morphine delivered using the AERx system in patients with moderate-to-severe asthma, Int. J. Clin. Pharmacol. Ther., 42,456-462. 

Olschewski, H., Rohde, B., Behr, J., et al. (2003), Pharmacodynamics and pharmacokinetics of inhaled iloprost, aerosolized by three different devices, in severe pulmonary hypertension, Chest, 124,1294—1304. 

Kinnula, V. Mattson, K. Cantell, K. Pharmacokinetics and toxicity of inhaled human interferon-alpha in patients with lung cancer. J. Interferon Res. 1989, 9, 419 23. Maasilta, P. Halme, J. Mattson, K. Cantell, K. Pharmacokinetics of inhaled recombinant and natural alpha interferon. Lancet 1991, 337, 371. 

Adjei AL, Qiu Y, Gupta PK. Bioavailability and pharmacokinetics of inhaled drugs. In Hickey AJ, ed. Inhalation Aerosols. New York Marcel Dekker, 1996. 

Freundt KJ, Schnapp E, Dreher W. 1975. Pharmacokinetics of inhaled carbon disulphide in rats in relation to its inhibitory effect on the side-chain oxidation of hexobarbital. Int Arch Occup Environ Health 35 173-186. 

Oral inhalation of insulin potentially offers noninvasive treatment and better glycemic control in diabetes by virtue of its apparently faster absorption into the systemic circulation compared with subcutaneous injection. However, the pharmacokinetics of inhaled insulin in the human lung has yet to be fully clarified because of the complexity of insulin-glucose physiology and the difficulty in approximating the inhaled dose. In 2004, Sakagami conducted a meta-analysis of... 

Isohanni MH, Neuvonen PJ, OUdcolaKT. Effect of itraconazole on the pharmacokinetics of inhaled lidoeaine. Basic Clin Pharmacol Toxicol (2004) 95, 120-3. 

Hung OR, Whynot SC, Varvel JR, Shafer SL, Mezei M. Pharmacokinetics of inhaled hposome-encapsulated fentanyl. Anesthesiology 1995 83(2) 277-284. 

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