Pulmonary pharmacology & therapeutics
-
Pulm Pharmacol Ther · Jan 2004
Randomized Controlled Trial Clinical TrialRelationship between neutrophil elastase and acute lung injury in humans.
We conducted clinical trials in patients with acute lung injury (ALI) associated with systemic inflammatory response syndrome using a selective neutrophil elastase inhibitor, sivelestat sodium hydrate (Sivelestat), to investigate the involvement of neutrophil elastase in ALI. In the phase III double-blind study (Study 1) in 230 patients, the efficacy of Sivelestat was evaluated with the pulmonary function improvement (PFI) rating as the primary endpoint, and the weaning rate from mechanical ventilator, the discharge rate from intensive care unit (ICU), and the survival rate as secondary endpoints. ⋯ VFD value in Study 2 was comparable to that in the optimal-dose group of Study 1 subgroup, and increase in VFD value correlated with PFI rating and increase in ICU free days. It was concluded that neutrophil elastase may be involved in the pathogenesis of ALI in humans.
-
Pulm Pharmacol Ther · Jan 2002
Randomized Controlled Trial Clinical TrialEffects of inhaled furosemide on CO(2) ventilatory responsiveness in humans.
We previously showed that inhaled furosemide improves experimentally induced dyspnea. In order to test the possibility that inhaled furosemide may alter the CO(2) chemosensitivity and thereby reduce the dyspneic sensation, the effect of inhaled furosemide on CO(2) chemosensitivity was evaluated with a double-blinded, randomized crossover design in 10 healthy subjects. ⋯ Our results showed that (1) inhaled furosemide does not affect the breathing patterns of resting breathing, (2) inhaled furosemide does not affect the slope and intercept of the CO(2) response curve, regardless of whether the CO(2) chemosensitivity is measured by the steady-state technique or rebreathing technique and (3) inhaled furosemide improves the dyspneic sensation produced during hypercapnic hyperpnea. These results suggest that the mechanism of the improvement of dyspnea by inhaling furosemide is not associated with the decrease in the ventilatory drive to CO(2).
-
Pulm Pharmacol Ther · Jan 1999
Randomized Controlled Trial Clinical TrialPharmacokinetics and pharmacodynamics of cumulative single doses of inhaled salbutamol enantiomers in asthmatic subjects.
Objectives of this study were to compare the pharmacokinetics, pharmacodynamics and safety of single cumulative doses of active (R)-salbutamol given either as the single enantiomer or racemic mixture by inhalation to subjects with mild to moderate asthma. This was a double-blind, crossover, cumulative-dose, randomized study where all subjects received either four doses of 1.25 mg of (R)-salbutamol or 2.5 mg of racemic (RS-) salbutamol by nebulization. The pharmacokinetic parameters were determined by noncompartmental analysis and model-fitting. ⋯ All pharmacodynamic parameters were similar whether (R)- or (RS)-salbutamol was given. The exposure to (R)-salbutamol was identical after inhalation of (R) -and (RS)-salbutamol by subjects with asthma. Several pharmacological responses including FEV(1)were also similar and there were no unique safety concerns with either treatment.