Effects of enprostil on cardiovascular and respiratory parameters in the dog, and on hematologic parameters in the rat, monkey, and human.
The effects of enprostil (+/-)-7-[(1R*,2R*,3R*)-3-hydroxy-2-[(E)-(3R*)-3-hydroxy-4-phenoxy-1- butenyl]-5-oxocyclopentyl]-4,5-heptadienoate) were studied on cardiovascular and respiratory parameters in the dog and on hematologic parameters in the rat, monkey, and human. Anesthetized dogs were instrumented to allow measurement of heart rate, systemic blood pressure, respiratory rate or tracheal pressure, and ventricular contractile force after intragastric (i.g.) or intravenous (i.v.) administration of enprostil in the presence or absence of autonomic challenges. The effects of intraduodenal (i.d.) enprostil on arterial and venous PO2, PCO2, and pH; respiratory rate, flow rate, and volume; blood pressure (b.p.); and heart rate were also examined. Enprostil i.v. (0.3-10 micrograms/kg) significantly increased tracheal pressure in a dose-dependent manner, but minimally altered b.p., heart rate, and ventricular contractile force. Enprostil i.v. (1-10 micrograms/kg) significantly inhibited pressor and depressor responses to several autonomic challenge agents at the highest dose level, indicative of a nonspecific inhibitory effect on b.p. responses. Cardiovascular effects of enprostil (1-100 micrograms/kg i.g.) were absent. Enprostil (10-3,000 micrograms/kg i.d.) had no noteworthy effects on respiratory parameters in the dog. Platelet aggregation effects of enprostil were studied in vitro using platelet rich plasma (PRP) from the rat, monkey, and human; whole blood clotting time and prothrombin time after oral enprostil were studied in the rat; and ex vivo effects on platelet activation were studied in humans.(ABSTRACT TRUNCATED AT 250 WORDS)
Johnson
L G
LG
Syntex Research, Palo Alto, CA.
Bruno
J J
JJ
Allely
M C
MC
Eglen
R M
RM
Chang
K
K
Yang
D
D
Alps
B J
BJ
Rosenkranz
R P
RP
Strosberg
A M
AM
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D004285:Dogs; D016620:Enprostil; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008252:Macaca fascicularis; D008297:Male; D010100:Oxygen / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects*; D012129:Respiratory Function Tests; D013045:Species Specificity
D011459:Prostaglandins E, Synthetic; D002245:Carbon Dioxide; D016620:Enprostil; D010100:Oxygen