Method for improvement of tolerance for therapeutically effective agents delivered by inhalation

A method for improvement of tolerance for and enhanced deposition of a therapeutically effective agent delivered into lungs of a human subject in need thereof by inhalation, said method comprising step of:

• treating said human subject with an aerosol consisting essentially of about 10 mg, 40 mg or 100 mg of lidocaine or lidocaine-like substituted acetanilide and benzamide compound aerosolized into an aerosol having particles with mass median aerodynamic diameter (MMAD) between 2 μm and 5 μm for targeted delivery into lower lungs, between 4 μm and 5 μm for targeted delivery into central lungs, and between 0.1 μm and 2 μm for targeted delivery into a systemic circulation, using an electronic nebulizer modified with a vibrating perforated membrane having an output from about 0.48 ml/minute to about 0.60 ml/minute and generating an aerosol with a monodisperse particle spectrum of said particles having a geometric standard deviation lower than 1.7;
• wherein said lidocaine or lidocaine-like substituted acetanilide or benzamide compound is dissolved in from about 1 ml to about 3 ml of saline having pH adjusted to between 5.0 and 7.5, osmolality between 150 and 550 mOsm/kg, permanent anion concentration between 31 and 300 mM of chloride, and viscosity lower than 1.5 centipoise, and aerosolized and delivered into lungs of the human subject in from about 1 to about 3 minutes, concurrently with, immediately before or within 30 minutes before inhalation of the therapeutically effective agent,
• wherein said treatment results in improved tolerance and enhanced deposition of said agent without occurrence of bronchospasm, numbing of pharyngeal area, loss of gagging reflex and tracheal aspiration;
• and
• wherein said therapeutically effective agent is selected from the group consisting of α-proteinase-inhibitor, amikacin, carbenicillin, ceftazidim, colistin, gentamycin, imipenem, ticarcillin, penicillin, tobramycin, vancomycin, aztreonam, fosfomycin, rifampicin, ciprofloxacin, guinolone, glutathion, pentamidine, nifedipine, verapamil, amiloride, benzamil, furosemide, piretanid, torasemid, heparin, cyclosporine, methotrexate, azathoprine, mycophenoline, sirolimus, tacrolimus, mofetil, α-interferone, β-interferone, γ-interferone, interleukin 2, adrenaline, retinoic acid, amphotericin B, cefoperazone, ciproflaxine, fentanyl, fusafungin, DNA, magnesium sulfate, dextrane, dornase α, hypertonic saline, mannitol, N-acetylcystein, nitroglycerine, nitroprusside sodium, morphine, prostaglandin, indomethacin, aminophylline, ribavirine and human growth factor.