Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of 9 beta-methyl carbacyclin, a chemically stable analogue of epoprostenol (prostacyclin, PGI2) were studied, in comparison with epoprostenol, both in vitro and in vivo in man. In vitro 9 beta-methyl carbacyclin and epoprostenol inhibited platelet aggregation induced by ADP, collagen, the endoperoxide analogue U46619 and arachidonic acid. The potency of 9 beta-methyl carbacyclin relative to epoprostenol was comparable in ADP and collagen-aggregated platelet rich plasma (PRP), 9 beta-methyl carbacyclin being 0.01 times as active as epoprostenol. The anti-aggregatory potencies of the two compounds were comparable in PRP and whole blood. The phosphodiesterase inhibitor isobutyl methyl xanthine enhanced the anti-aggregatory activity of both compounds in vitro. 9 beta-methyl carbacyclin and epoprostenol elevated platelet cyclic AMP, 9 beta-methyl carbacyclin being 0.04 times as active as epoprostenol. In a placebo controlled trial both drugs produces significant headache and facial flushing when compared with placebo. Nasal stuffiness, abdominal discomfort and nausea were reported on all three treatments. Both drugs caused significant and comparable increase in heart rate and decrease in pre-ejection (PEP) and PEP/left ventricular ejection time (LVET) ratio compared with placebo. Systolic and diastolic blood pressure, LVET and QS2 index were unchanged. Platelet aggregation responses to ADP were significantly inhibited by all three doses of both drugs compared with placebo. Bleeding time was significantly longer during epoprostenol infusion than either placebo or 9 beta-methyl carbacyclin infusion. Neither drug had significant effect, compared with placebo, on kaolin activated clotting time in PPP, PRP or in PRP in the presence of heparin, prothrombin time, partial thromboplastin time, thrombin clotting time, fibrinogen, fibrinogen degradation products or euglobulin clot lysis time. The pharmacodynamic effects and duration of action of 9 beta-methyl carbacyclin and of epoprostenol are similar; 9 beta-methyl carbacyclin is approximately 100 times less potent than epoprostenol in man.
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PMID:A chemically stable analogue, 9 beta-methyl carbacyclin, with similar effects to epoprostenol (prostacyclin, PGI2) in man. 608 4

Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, works intracellularly within immune cells to regulate inflammatory mediators. This phase 2b randomized, placebo-controlled study evaluated efficacy and safety of apremilast among Japanese patients with moderate to severe plaque psoriasis. In total, 254 patients were randomized to placebo, apremilast 20 mg b.i.d. (apremilast 20) or apremilast 30 mg b.i.d. (apremilast 30) through week 16; thereafter, all placebo patients were re-randomized to apremilast 20 or 30 through week 68. Efficacy assessments included achievement of 75% or more reduction from baseline in Psoriasis Area and Severity Index score (PASI-75; primary) and achievement of static Physician Global Assessment (sPGA; secondary) score of 0 (clear) or 1 (minimal) at week 16. Safety was assessed through week 68. At week 16, PASI-75 response rates were 7.1% (placebo), 23.5% (apremilast 20; P = 0.0032 vs placebo) and 28.2% (apremilast 30; P = 0.0003 vs placebo); sPGA response rates (score of 0 or 1) were 8.8% (placebo), 23.9% (apremilast 20; P = 0.0165 vs placebo) and 29.6% (apremilast 30; P = 0.0020 vs placebo). Responses were maintained with apremilast through week 68. Most common adverse events (AEs) with placebo, apremilast 20 and apremilast 30 (0-16 weeks) were nasopharyngitis (8.3%, 11.8%, 11.8%), diarrhea (1.2%, 8.2%, 9.4%), and abdominal discomfort (1.2%, 1.2%, 7.1%), respectively. Exposure-adjusted incidence of these AEs did not increase with continued apremilast treatment (up to 68 weeks). Apremilast demonstrated efficacy and safety in Japanese patients with moderate to severe plaque psoriasis through 68 weeks that was generally consistent with prior studies.
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PMID:Apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of Japanese patients with moderate to severe plaque psoriasis: Efficacy, safety and tolerability results from a phase 2b randomized controlled trial. 2839 57

Apremilast is a novel oral phosphodiesterase 4 inhibitor effective for psoriasis. It regulates the production of pro-inflammatory mediators. Apremilast was approved in December 2016 in Japan; however, its efficacy and safety in a real-world setting among Japanese patients have not been reported. We report on 44 patients treated with apremilast between March and October 2017. The median treatment duration was 25 weeks (range, 2-33). Thirty-five patients (79.5%) continued the drug for at least 23 weeks, and five (11.4%) achieved a Psoriasis Area and Severity Index 100 response within 12 weeks. Nine patients discontinued the drug within 24 weeks mainly due to insufficient efficacy (n = 3) and adverse events (n = 4). Seven patients continued their previous systemic therapies such as cyclosporin (n = 1), methotrexate (n = 1), etretinate + methotrexate (n = 1) and biologics (n = 4) combined with apremilast. Of these patients, 55.9% had at least one adverse event although no severe adverse events. The most common adverse event was diarrhea (31.8%), followed by nausea (25.0%), headache (13.6%), abdominal discomfort (6.8%) and vomiting (6.8%). The proportion of diarrhea in our patients was higher than those of previous clinical trials. Among 10 patients with psoriatic arthritis, apremilast did not improve joint pain in nine (90%). To investigate the relationship between treatment efficacy and plaque size, we defined a small plaque as an individual rash diameter of 1 inch or less. The efficacy of apremilast was greater in patients with small plaques than in patients with large plaques.
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PMID:Real-world use of apremilast for patients with psoriasis in Japan. 3016 80