Clinical pharmacology of 2, 3-dichloro-4-methoxyphenyl 2-furyl ketone (E)-0- [2-(diethylamino) ethyl] oxime (ANP 4364) in healthy volunteers

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A newly synthesized ketone oxime derivertive, 2, 3-dichloro-4-methoxyphenyl 2-furyl ketone (E)-0- [2-(diethylamino) ethyl] oxime (ANP 4364), was administered orally to 6 healthy volunteers to investigate its safety, pharmacodynamics, and pharmacokinetics. Six volunteers received single oral doses of 50, 100, 200 mg, and 3 consecutive doses of 100 mg, of ANP 4364. ANP 4364 caused slight hypotension, with a transient tachycardia, and a tendency towards increasing stroke volume revealed by impedance cardiography. No findings attributable to the drug were observed in the ECG or body temperature records. Pharmacokinetic analysis revealed that unchanged ANP 4364 was rapidly absorbed with a mean half-life of about 10 hours. After administration of 100 mg, 0.16% of the dose of ANP 4364 was excreted in urine within 24 hours. Subjective symptoms possibly produced by the drug were headache, a heavy feeling of the head, a feeling of warmth in the face, and numbness of the tongue ; there was one subject, however, who complained of nausea. Examination of the blood and urine showed no abnormal findings attributable to administration of the drug. In conclusion, it was found that ANP 4364 seems to have vasodilating action and is well-tolerated in man.
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