Effect of a hydantoin prostaglandin analogue, BW245C, during oral dosing in man.
Following an open pilot study, the effects of repeated oral doses of BW245C, a hydantoin prostaglandin analogue, were studied in man. Six healthy volunteers received 150 micrograms BW245C or placebo 6-hourly for 5 days according to a double blind randomised balanced design with 7 days interval between treatments. Measurements of headache, facial flushing, heart rate, blood pressure, systolic time intervals, ECG, platelet aggregation responses to ADP and of subjective effects were made before and 1 and 3 h after the first dose of BW245C/placebo on days 1, 3 and 5 of dosing. BW245C produced significantly (p less than 0.05) higher headache scores than placebo on days 3 and 5; facial flushing, nasal stuffiness and abdominal discomfort were more frequent on BW245C than placebo. Heart rate, derived from the ECG, was significantly (p less than 0.05) higher and pre-ejection period significantly (p less than 0.05) shorter on BW245C at 1 h after dosing on each day. Left ventricular ejection time index, QS2 index, PR interval, QRS duration and T wave height were unchanged. Heart rate, counted at the radial pulse, and systolic and diastolic blood pressure, all measured lying and standing, were similar for BW245C and placebo. Platelet aggregation responses were not significantly different between the two treatments. The results indicate that repeated oral doses of BW245C, sufficient to cause moderately uncomfortable subjective effects, do not inhibit platelet aggregation.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000284:Administration, Oral; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004341:Drug Evaluation; D004562:Electrocardiography; D005483:Flushing; D006261:Headache / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006827:Hydantoins / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects
D006827:Hydantoins; D000244:Adenosine Diphosphate; C030669:BW 245C