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Smoking accelerates absorption of inhaled neutrophil elastase inhibitor FK706

Fumiaki Koizumi MD1, Manabu Murakami MS1, Hiromitsu Kageyama MS1, Masataka Katashima PhD1, Masato Terakawa PhD1 and Akihiro Ohnishi MD, PhD1

1Department of Internal Medicine, Daisan Hospital, Jikei University School of Medicine, and also the Department of Laboratory Medicine, Daisan Hospital, Jikei University School of Medicine, Tokyo, as well as the Exploratory Clinical Research Development Division, Fujisawa Pharmaceutical Co, Ltd, as well as the Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co, Ltd, Osaka, Japan

Correspondence: Akihiro Ohnishi, MD, PhD, Departments of Internal Medicine and Laboratory Medicine, Daisan Hospital, Jikei University Med school, 4111 Izumihoncho, Komae, Tokyo 2018601, Japan.

Received 23 April 1999; Accepted 17 August 1999.

Surface of pageAbstractPurpose: We compared the pharmacokinetics with the inhaled novel neutrophil elastase inhibitor FK706 between healthy nonsmokers and smokers.

Methods: Six healthy nonsmokers and 6 smokers inhaled 50 to 400 mg FK706 in 2 different doses. Series of plasma concentrations with the SSS kind of FK706 (pharmacologically active epimer) were analyzed model dependently and independently. Pharmacokinetic parameters from each group were compared after standardization by doses.

Results: The plasma concentration curve of inhaled FK706 was apparently different between smokers and nonsmokers. The utmost plasma concentrations (Cmax) were significantly higher within the smokers than in the nonsmokers (smokers, 1.47 0.62 ng/mL/mg; nonsmokers, 0.49 0.14 ng/mL/mg <mean>SD; P max (tmax) and elimination halflife (t were statistically smaller in the smokers compared with the tmax and elimination t in the nonsmokers (tmax in smokers, 0.44 0.27 hours; tmax in nonsmokers, 1.17 0.39 hours <P>in smokers, 1.23 0.40 hours; t in nonsmokers, 2.73 0.57 hours <P>a) concerned Ten times greater in smokers compared to ka in nonsmokers.

Conclusion: Significant increases of Cmax and ka and reductions of tmax and elimination t of the inhaled FK706 were affecting the healthy smokers, suggesting how the smoking habit accelerates the drug absorption after inhalation. These results claim that we have to pay attention to the drugrelated adverse events brought on by smoking, particularly when the drug includes a narrow therapeutic range.

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