Pharmacology and Toxicology of Carbetocin

pharmacological action
Carbetocin is a synthetic long-acting oxytocin 9-peptide analogue with agonist properties. A single dose of intravenous medication can be administered immediately after cesarean section under epidural or spinal anesthesia to prevent uterine hypotension and postpartum hemorrhage.
The clinical and pharmacological properties of carbetocin are similar to those of naturally occurring oxytocin. Like oxytocin, carbetocin binds to the oxytocin receptor of uterine smooth muscle, causing rhythmic contraction of the uterus, increasing its frequency and increasing uterine tension on the basis of the original contraction. In non pregnant states, the content of oxytocin receptors in the uterus is very low, increasing during pregnancy and reaching a peak during childbirth. Therefore, carbetocin has no effect on non pregnant uterus, but has an effective uterine contraction effect on pregnant uterus and newly born uterus.
After intravenous or intramuscular injection of carbetocin, the uterus contracts rapidly, reaching a clear intensity within 2 minutes. The active effect of a single dose of intravenous injection of carbetocin on the uterus lasts about one hour, and is therefore sufficient to prevent postpartum hemorrhage immediately after birth. After postpartum administration of carbetocin, the frequency and amplitude of contraction are longer than oxytocin.
Studies have shown that when a single dose of 100 micrograms of carbetocin is administered intravenously immediately after cesarean section under epidural or spinal anesthesia, carbetocin is significantly superior to placebo in preventing uterine hypotension and reducing postpartum hemorrhage.
Administration of carbetocin in the early postpartum period can also promote uterine involution.
Toxicological Studies
In the acute toxicity study, LD50 was investigated by intravenous injection of 10 mg/kg into rats. Record the clinical manifestations of all animals (lethargy, hunching posture, bristling, shortness of breath, and motor incoordination). According to the LD50 value, the dose administered to 100 grams of rats is 1000 micrograms, which is 10 times the dose used by humans.
Twenty rats were divided into four groups and given cabetocin 1.0 mg/kg intravenously every day. There were no treatment-related deaths or clinical manifestations after 28 days.
Sixteen female hounds were given cabetocin 1.0 mg/kg/day intravenously every day. After 28 days, there were no deaths or clinical signs related to the administration. There were also no treatment-related changes in hematology, clinical biochemistry, or urinalysis.
No mutagenic effect was found in the mutagenic experiment with carbetocin.
No carcinogenic experimental studies have been conducted.
Because the drug is administered in a single dose early after childbirth, no reproductive and teratogenic experiments have been conducted