Smoking accelerates absorption of inhaled neutrophil elastase inhibitor FK706

Abstract

Significant increases of Cmax and ka and reductions of tmax and elimination t1/2 of the inhaled FK706 were observed in the healthy smokers, suggesting that the smoking habit accelerates the drug absorption after inhalation. These results suggest that we should pay attention to the drug-related adverse events caused by smoking, especially when the drug has a narrow therapeutic range.

Flip-flop Pharmacokinetics – Delivering a Reversal of Disposition: Challenges and Opportunities During Drug Development

“…Interestingly, the smokers demonstrated a shorter t max and a shorter elimination half-life (1.23 ± 0.40 h vs 2.73 ± 0.57 h, respectively) [148]. k a was reported to be ten-times greater in smokers than nonsmokers.…”

“…These findings may suggest that smoking causes increasing pulmonary epithelial permeability. FK706 is a small hydrophilic molecule and this phenomenon could apply to other xenobiotics that are delivered to the lungs with similar physicochemical properties [148]. …”

Characterization of Perioperative Leukocytosis in Patients undergoing Robotic assisted Retropubic Prostatectomy: Effects of Gleason score and Race

“…Serum from patients with cancer has been shown to inhibit neutrophil chemotaxis [20] and phagocytosis. [21] Which of these processes has a larger contribution to the development of malignancies is unknown. Whether it is an inherent defect in neutrophil cytotoxicity allowing malignancies to develop or rather the cancers' ability to impair neutrophils that is primarily responsible for carcinogenesis has yet to be determined.…”

Characterization of Perioperative Leukocytosis in Patients Undergoing Robot-Assisted Radical Prostatectomy: Effects of Gleason Score and Race

“…Serum from patients with cancer has been shown to inhibit neutrophil chemotaxis 20 and phagocytosis. 21 Which of these processes has a larger contribution to the development of malignancies is unknown. Whether it is an inherent defect in neutrophil cytotoxicity allowing malignancies to develop or rather the cancers' ability to impair neutrophils that is primarily responsible for carcinogenesis has yet to be determined.…”