Following an open pilot study,
BW 245C , a
hydantoin prostaglandin analogue, was given by mouth in an aqueous
solution to six healthy volunteers. The subjects received
BW 245C 50 and 150 micrograms and placebo on separate occasions according to a double blind randomised design. Heart rate, blood pressure and, using visual analogue scales, facial
flushing, abdominal discomfort and
headache, were measured before dosing, at 15 minute intervals after dosing for 2 hours and at 30 minute intervals for a further 2 hours. Platelet aggregation responses to
ADP and to
collagen were measured before dosing and at 15 minutes, 45 minutes, 2 hours and 4 hours after dosing. Cutaneous bleeding time was measured before and 45 minutes after dosing. 150 micrograms
BW 245C produced significant (p less than 0.05) facial
flushing over the period from 15 to 120 minutes after dosing. Heart rate increased slightly but significantly (p less than 0.05) in response to both doses of 245C only at 75 minutes after dosing. Systolic and diastolic blood pressures were unchanged by either dose of
BW 245C . Platelet aggregation responses to
ADP were significantly (p less than 0.05) inhibited only at 120 minutes after 150 micrograms
BW 245C . Aggregation responses to
collagen were significantly (p less than 0.05) inhibited 45 and 120 minutes after 150 micrograms
BW 245C and also at 120 minutes after 50 micrograms
BW 245C . Bleeding time was unchanged in response to either dose of
BW 245C . There was no change in
headache or abdominal discomfort scores following either dose of
BW 245C .
Nausea was reported after 7 out of 12 administrations of BW245C but not after placebo. Nasal congestion was experienced by two subjects receiving 150 micrograms
BW 245C and muscle tension and stiffness, especially of the jaw muscles, was also reported following administration of
BW 245C but not of placebo.
BW 245C is active when given by mouth and has similar pharmacodynamic effects to
prostacyclin in man.