Prucalopride
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| Non-proprietary name | Prucalopride | |||||||||||||||
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| Molecular formula | C 18 H 26 ClN 3 O 3 | |||||||||||||||
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| Molar mass | 367.87 g · mol -1 | |||||||||||||||
| density |
1.28 g cm −3 |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||||||||
Prucaloprid (trade name Resolor ® ; manufacturer Shire ) is a drug from the group of prokinetics .
Clinical information
application areas
Prucalopride is used in the treatment of chronic constipation in adults in whom laxatives have not been sufficiently effective .
Type and duration of application
The recommended dose is 2 mg prucalopride once a day and it can be taken with or without food. According to the manufacturer, increasing the dose does not increase the effectiveness. If the symptoms have not improved after four weeks of use, the therapy should be reconsidered.
Contraindications
Prucalopride should not be taken at
- known hypersensitivity to the substance,
- renal failure requiring dialysis ,
- Intestinal perforation and
- various intestinal diseases such as B. intestinal obstruction , Crohn's disease , ulcerative colitis or toxic megacolon .
Drug interactions
Due to a hitherto unknown mechanism, simultaneous administration with erythromycin leads to an increase in the plasma level of the same of about 30%, while strong inhibitors of CYP3A4 increase the serum concentrations of prucalopride by 40%.
Use during pregnancy and breastfeeding
Women of childbearing potential should use effective contraception while taking it, as spontaneous abortions have been seen in clinical studies with prucalopride . Because the active ingredient passes into breast milk, it should not be used during breastfeeding.
Special patient groups
Elderly patients should start with a daily dose of 1 mg, which can be increased to 2 mg if necessary, as well as in patients with severe hepatic impairment ( Child-Pugh class C). Patients with severe renal impairment ( GFR <30 ml / min / 1.73 m 2 ) should receive 1 mg as the maximum daily dose, while no dose adjustment is required in patients with less impaired renal function. Prucalopride should not be used in children and adolescents.
unwanted effects
The following ADRs can occur during treatment :
- very common: headache, nausea, diarrhea, abdominal pain
- common: decreased appetite, dizziness, vomiting, indigestion, flatulence, abnormal abdominal noises, fatigue
- uncommon: tremors, rectal bleeding, pollakiuria , fever, malaise.
Pharmacological properties
Mechanism of action
Prucalopride is a (highly selective) agonist at serotonin ( 5-HT 4 ) receptors , which are located in the intestinal wall. The acetylcholine release triggered by the receptor activation leads to increased peristalsis of the gastrointestinal tract and thus to an accelerated intestinal passage of the food pulp, which in turn causes an improved defecation. Animal experiments have shown that prucalopride acts as an antagonist at dopamine D 2 receptors in higher doses and increases the prolactin level in the blood via this mechanism . Prucalopride also inhibits the HERG channel subunit , but not at therapeutic doses either.
Absorption and distribution in the body
Prucalopride is rapidly absorbed with a bioavailability of more than 90% independent of food intake ; maximum plasma concentrations are reached after 2 mg orally after 2–3 hours. The volume of distribution is 567 liters and protein binding is about 30%. About 65% of the excretion is unchanged via the kidneys.
toxicology
After an overdose of prucalopride, the side effects become more pronounced, and there may also be a moderate increase in pulse and blood pressure. A causal therapy is not known, the treatment is symptomatic.
Other Information
History
Resolor ® was approved in the EU in January 2010 and in Switzerland at the end of July of the same year.
Studies
The approval of Resolor ® is based on three double-blind , randomized and placebo-controlled studies in which about 1300 patients with chronic constipation took part, 88% were women. The daily dose was 2 or 4 mg once a day. The endpoint was defined as the number of patients who were completely emptied of their bowels at least three times a week over a period of 12 weeks without any further administration of laxatives. Prucalopride was superior to placebo at both dosages . However, the dosage of 4 mg / d did not bring any significant advantages over that of 2 mg / d.
See also
Individual evidence
- ↑ a b c d Prucaloprid from Selleckchem.Retrieved July 16, 2016.
- ↑ Prucaloprid at ChemNet.Retrieved July 16, 2016.
- ↑ a b Safety data sheet prucalopride Retrieved on July 16, 2016.
- ↑ a b c d e f g h i j Specialist information Resolor ® (PDF) Shire, March 2012. Accessed December 31, 2016.
- ↑ a b c d e f g Red List 2015. Rote Liste Service GmbH, Frankfurt / Main, 2015.
- ↑ a b Pharmazeutische Zeitung 56/2010. Accessed December 31, 2016.
- ↑ a b c d arznei-telegram 41/2010. Accessed December 31, 2016.
- ↑ a b Entry on prucalopride in the Pharmawiki , accessed on December 31, 2016.
Trade names
Monopreparations : Resolor ®
