Abstract

ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF DOXOFYLLINE

Shraddha Jayant Bhangre*, Suhas S. Siddheshwar and Prof. Mahesh Kolhe

Abstract

Doxofylline is an effective bronchodilator for relieving airway obstruction in patients with asthma or chronic obstructive pulmonary disease (COPD), and displays a better safety profle with respect to theophylline. Here, we performed a pairwise analysis of the currently available data to provide consistent and homogeneous fndings on the impact of this xanthine in COPD patients. Results obtained from 820 patients were selected from 20 clinical trials. Meta-regression was performed to examine the source of heterogeneity between-studies and identify potential confounder covariates. The quality of the evidence was assessed by the GRADE system. Doxofylline induced a signifcant (P < 0.001) increase in forced expiratory volume in 1s (FEV1) of 8.20% (95%CI 4.00–12.41; I2 93%) and 317ml (95%CI 19–439; I2 87%) compared with baseline. The total administered dose of doxofylline signifcantly (P < 0.001) interacted with the size of the effect estimates detected for FEV1. Doxofylline induced a signifcant (P < 0.001), although moderate, increase in adverse events (AEs) frequency (proportion 0.03, 95%CI 0.02–0.04; I2 88%), but only epigastralgia, nausea, dyspepsia and headache were statistically signifcant (P < 0.05). The GRADE analysis indicated high quality of evidence (++++) for the impact of doxofylline on FEV1, and moderate quality of evidence (+++) for the safety profle in COPD patients. Doxofylline is an effective and safe medicine when administered to patients with COPD and can be considered as an alternative to theophylline.

Keywords: Doxofylline Chronic obstructive pulmonary disease Lung function Safety Pairwise.