Oglemilast

PDE4 inhibitors have been in development as a novel anti‐inflammatory therapy since the 1980s with asthma and chronic obstructive pulmonary disease (COPD) being primary indications. Despite initial optimism, none have yet reached the market. In most cases, the development of PDE4 inhibitors of various structural classes, including cilomilast, filaminast, lirimilast, piclamilast, tofimilast, AWD‐12‐281 (aka GSK 842470), CDP840, CI‐1018, D‐4418, IC485, L‐826,141, SCH 351391 and V11294A has been discontinued due to lack of efficacy. A primary problem is the low therapeutic ratio of these compounds, which severely limits the dose that can be given. Indeed, for many of these compounds it is likely that the maximum tolerated dose is either sub‐therapeutic or at the very bottom of the efficacy dose‐response curve. Therefore, the challenge is to overcome this limitation. It is, therefore, encouraging that many ‘new(er)’ PDE4 inhibitors in development are reported to have an improved therapeutic window including tetomilast, oglemilast, apremilast, ONO 6126, IPL‐512602 and IPL‐455903 (aka HT‐0712), although the basis for their superior tolerability has not been disclosed. In addition, other approaches are possible that may allow the anti‐inflammatory activity of PDE inhibitors to be realized. Accordingly, this Commentary endorses the view of Spina (2008), published in the current issue of the British Journal of Pharmacology, that the therapeutic utility of PDE4 inhibitors to suppress inflammation still remains a viable concept.British Journal of Pharmacology (2008) 155, 288–290; doi:fn1; published online 28 July 2008

Oral Type 4 phosphodiesterase inhibitors (e.g. roflumilast) have provided evidence of clin. efficacy in both asthma and chronic obstructive pulmonary disease (COPD).The objectives were to evaluate the efficacy, safety and tolerability of oglemilast at 3 dose levelscompared with placebo for the treatment of mild to moderate persistent asthma, to investigate the pharmacokinetics of oglemilast and its N-oxide metabolite, to investigate the effects of oglemilast on pharmacodynamics parameters in sputum and blood.This is a randomized, double-blind, placebo controlled, parallel group phase II study to evaluate the efficacy of 3 doses (0.2, 0.4, 0.8 mg) of drug-x administered for 12 wk once daily.A total of 30 patients of mild to moderate persistent asthma were screened.From the 30 patients, total 27 patients are eligible for randomization and they get the Drug-x as well as placebo.In the study, the spirometry and symptom score which are recorded by the patient in their dairy for evaluation of result of the study were taken.Patients brought for the study medication their paper diary to every study visit.Safety status assessed by clin. laboratory tests, vital signs, phys. examination (including ECG [ECG]), monitoring of asthma symptoms and adverse events.It was seen that patients who received the Drug-x shows marked improvement in spirometry parameters from visit V1 to visit Vend.Drug-x has significant safety profile and it can be used for management of asthma.