Disease relevance of Carbetocin

• CONCLUSIONS: Carbetocin, a new drug for the prevention of uterine atony, appears to be more effective than a continuous infusion of oxytocin and has a similar safety profile [1].
• Comparison of carbetocin and oxytocin for the prevention of postpartum hemorrhage following vaginal delivery:a double-blind randomized trial [2].

High impact information on Carbetocin

• Although carbetocin has not yet been studied immediately postpartum, its prolonged uterine activity suggests that carbetocin may offer advantages over oxytocin in management of the third stage of labor [3].
• Effect of carbetocin, a long-acting oxytocin analog on the postpartum uterus [3].
• Double-blind comparison of carbetocin versus oxytocin in prevention of uterine atony after cesarean section [1].
• Carbetocin is an important drug with recognized therapeutical application for stimulation of uterine contractions to facilitate parturition [4].
• However, maximal contractile effect of carbetocin was approximately 50% lower than that of oxytocin (2.70 +/- 0.12 g compared to 5.22 +/- 0.26 g) and EC50 was approximately ten times higher (48.0 +/- 8.20 nM compared to 5.62 +/- 1.22 nM) [5].

Biological context of Carbetocin

• RESULTS: For plasma, the mean (+/- standard deviation) area under the curve (AUC) of carbetocin versus time was 1119.3 +/- 315.9 pg/mL, a value about 50 times higher than the mean AUC for carbetocin in breast milk (18.6 +/- 13.7 and 29.0 +/- 23.8 pg/mL for the right and left breast, respectively) [6].
• At Day 7 after ovulation, mares had to undergo four treatments in a crossover design: (a) control, (b) oxytocin (10 IU i.v.), (c) carbetocin (280 microg i.m.) and (d) cervical dilation [7].
• OBJECTIVE: To determine the maximum tolerated dose (MTD) of carbetocin (a long-acting synthetic analogue of oxytocin), when administered immediately after vaginal delivery at term [8].
• MATERIALS AND METHODS: Carbetocin was given as an intramuscular injection immediately after the birth of the infant in 45 healthy women with normal singleton pregnancies who delivered vaginally at term [8].
• The main product emerging after treatment of carbetocin with chymotrypsin is 9-desglycineamide carbetocin indicating preferential hydrolysis of the peptide bond between leucine at position 8 and carboxyterminal glycineamide [9].

Anatomical context of Carbetocin

• Transfer of carbetocin into human breast milk [6].
• The fundus was below the umbilicus in more patients who received carbetocin at 0, 2, 3, and 24 hours on the ward (p < 0.05) [10].
• The contractile effect of the analogue 1-deamino-1-carba-2-tyrosine (0-methyl)-oxytocin (carbetocin) on isolated strips from the human myometrium was compared with that of oxytocin [11].
• Despite the low biological activity of carbetocin, its binding affinity to receptors of isolated myometrial plasma membranes was of the same order of magnitude as that of oxytocin [12].

Associations of Carbetocin with other chemical compounds

• These results indicate that carbetocin is a partial agonist/antagonist to the oxytocin receptor while the two metabolites carbetocin metabolite I and carbetocin metabolite II are pure antagonists [5].
• In conclusion, the present study showed that single administration of oxytocin or its long-acting analogue carbetocin at Day 7 after ovulation did not affect progesterone secretion, pregnancy rate and embryonic growth [7].
• Compared with control animals, restraint stress induced a higher accumulation of AVP (+41%), DGAVP (+60%), carbetocin (+81%) and GnRH (+104%) [13].

Gene context of Carbetocin

• Oxytocin receptor binding and uterotonic activity of carbetocin and its metabolites following enzymatic degradation [5].
• Only carbetocin bound to the renal vasopressin V2 receptor though the binding affinity was very low (61.3 +/- 14.6 nM) [5].
• The first group (n = 9) was administered 50 IU oxytocin intramuscularly, the second group (n = 10) received 0.35 mg carbetocin, while animals of the third group (n = 8), serving as a control, were administered 5 mL saline solution [14].
• Carbetocin, an oxytocin receptor agonist, shows promise but has not been evaluated for use after vaginal births [15].
• Neither oxytocin nor carbetocin affected contractile activity in strips from non-pregnant women, but both peptides stimulated contractile activity in strips from women at term pregnancy (2 x 10(-11) mol/l, and 10(-10) mol/l, respectively) [11].

Analytical, diagnostic and therapeutic context of Carbetocin

• Carbetocin, a long-acting oxytocin analog, was administered by intravenous and intramuscular injection to 40 women 24 to 48 hours postpartum [3].
• Separation and identification of peptide mixtures in a synthesis crude of carbetocin by liquid chromatography/electrospray ionization mass spectrometry [4].
• The odds of treatment failure requiring oxytocic intervention was 2.03 (95% confidence interval 1.1 to 2.8) times higher in the oxytocin group compared with the carbetocin group, respectively, 32 of 318 (10.1%) versus 15 of 317 (4.7%), P <.05 [1].
• Using a radioimmunoassay, the concentrations of carbetocin were measured in plasma and breast milk samples obtained before carbetocin administration and at 15, 30, 60, 90, 120, and 240 minutes after drug administration [6].
• On Day 13, all mares (8 of 8 mares) were pregnant on groups control, oxytocin and carbetocin and only 6 of 8 mares on group dilation [7].

References