Effect of AS-4370 on gastric motility in patients with diabetic autonomic neuropathy.

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Delayed gastric emptying in diabetic patients occurs with progress of autonomic neuropathy as one late complication. Delayed emptying is deeply correlated with poor glycemic control, due to imbalance between nutrients absorption and effect of exogenous insulin. AS-4370 is a newly developed prokinetic agent which has been reported to selectively activate motility of the upper gastrointestinal tract through enhancing acetycholine release from nerve terminals within the enteric mural plexus. In this study, we evaluated the effect of AS-4370 on gastric motility in diabetic patients with autonomic neuropathy. Eight diabetic patients with autonomic neuropathy (3 males and 5 females) with mean age of 56 years old (range 29-66) participated to this study after giving written informed consent. Gastric motility was evaluated by gastric emptying and electrogastrography. Gastric emptying study was done using <SUP>99m</SUP>Tc-Tin colloid labeled omelet meal served with 2 slices of toast and 200 ml of milk. Electrogastrography was recorded from epigastric skin surface, for 30 minutes before and after meal each. AS-4370, 7.5 mg tid, was given for four weeks after basal recording of gastric motility studies. Following the 4-week treatment with AS-4370, gastric motility studies were repeated. For the motility studies after medication, drug was given 30 minutes before test meal. Gastric retention rate at 150 minutes in all patients were over 45% of upper limit of normal range in basal study with mean value of 69 ± 5%, which decreased significantly to 52±5%, with AS-4370 treatment (p<0.01). Gastric emptying speed, another parameter for gastric emptying also improved with medication. In electro-gastrographic studies, duration of 3 cpm waves (2.8-3.2 cpm waves) in 30 minutes both before and after meal increased with AS-4370 treatment. Though the decrease of pre-prandial glycemic level was insignificant, HbAl level decreased after treatment significantly. In conclusion, AS-4370 improved gastric dysmotility, both delayed gastric emptying and abnormality in electrogastrography, in diabetic patients with autonomic neuropathy and improved glycemic control.
日本平滑筋学会の論文

Effect of AS-4370 on gastric motility in patients with diabetic autonomic neuropathy.

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