Carboprost

Carboprost is a synthetic 15-methyl analogue of dinoprost (prostaglandin F2 alpha). It is a uterine stimulant with a more prolonged action than dinoprost and when used in post-partum haemorrhage, it stimulates the uterus to contract in a manner similar to that normally observed in the uterus following delivery. The resulting myometrial contractions provide haemostasis at the site of placentation and hence prevent further blood loss. Whether or not this action results from a direct effect on the myometrium has not been determined with certainty at this time. The fundamental actions of the prostaglandins include inhibition or stimulation of smooth muscle contraction and inhibition of the release of noradrenaline or modulation of its effects at neuroeffector sites. They affect the uterus, the cardiovascular system, the gastro-intestinal system, the nervous system, the urinary system and metabolic processes.

The presence of the methyl group delays inactivation by enzymic dehydrogenation.

Peak plasma levels vary depending on the route of administration. In the Rhesus monkey after a single i.m. injection of 20-30 micrograms of 15-methyl PGF2 alpha peak levels of 0.4-5 nanograms/ml resulted at 30-60 minutes, declining to baseline levels 6-8 hours after injection. In pregnant women, an i.m. injection of 100-400 micrograms resulted in peak plasma levels of 1-1.6 nanograms/ml 20-30 minutes after injection. Levels declined to 0.2-0.4 nanograms/ml after 3 hours. When i.m. doses of 250 micrograms were given every two hours, pre-injection plasma levels stabilised after four injections at 1.2 nanograms/ml.

After administration of 2.5 mg 15-methyl PGF2 alpha intra-amniotically to 5 subjects, plasma levels were from 100-580 picograms/ml during the first 15 hours after administration. In three subjects the levels were low and fairly constant, while the two other had higher, but more variable levels.