Patent MX-2008012889-A (MX)
Title: Assessment of an extemporaneous suspension of propafenone for paediatric purposes.
Inventor: MATEO HUGO JUAREZ OLGUIN
IPC: A61K31/00
Filed: 2008-10-06
Abstract: Supraventricular tachycardias (SVT) are arrhythmias caused by the abnormal, rapid and paroxistic formation of the electric impulse of the heart, are tachyarrhythmias that start and stay in the auricular or atrioventricular tissue. The frequency of the SVT is present in 1 of 250 children, 40% of the paediatric population presenting them has factors that predispose said disease, such as congenital malformations, fever or the presence of adverse reactions due to drug exposure. Propafenone (PPF) is a 1c type antiarrhythmic agent, sodium channel blocker, b-adrenergic receptor antagonist. Said antiarrhytmic agent is efficiently and safely used for treating the aforesaid type of tachycardia due to the above mentioned characteristics. Due to the fact that in Mexico a PPF presentation for children is not currently available, errors in dosing occur since children find difficult to swallow tablets. As a temporal solution, physicians or nurses used to fraction the drug in order to provide the c hild with the required amount of the medication according to its weight, without being certain of administering an accurate dose. Said situation is a matter of concern for the physician, since the metabolism of the PPF is measured by the CYP2D6 enzyme and is sensitive to saturation, thereby small increases of the dose may follow unmeasured amounts of the PPF plasmatic concentration, consequently having serious adverse effects. The present invention is intended to develop and assess an extemporaneous suspension of propafenone for paediatric purposes, and study the pharmacokinetic behaviour thereof after being administered to paediatric patients. Said assessment is of great clinical concern, since the product developed in suspension may offer an alternative for those children that require the administration of said medication in an accessible manner and allow to have a better control of the administered dose. Process. The first stage of the process consisted in the development of the an alytical methodology by a High Performance Liquid Chromatography (HPLC), which is required to pass to the following phases. An oral PPF suspension was subsequently prepared at a concentration of 1.5 mg/ mL, using grenadine syrup as a vehicle, where the physiochemical and microbiological stabilities of said preparation were assessed, the product being stored at room temperature (15?C to 5?C) and in refrigeration (3?c to 5?C) for a period of time of 90 days. The PPF quantification was carried out by an HPLC method, and being based on the research recently published by this laboratory. The third stage consisted on the development of a bioavailability study of the drug in an animal model (Phase I) for assessing the reliable use thereof in humans. The following stage consisted on conducting the aforementioned study of the developed formula, but this time in a group of health volunteers (Phase II), both phases showed results similar to those reported by other authors. Clinical Use. The pres ent invention is of clinical importance, since the product developed in suspension is an advantage for those children that require the administration of the drug in an accessible manner. For that purpose, the most important part of the project is, doubtlessly, the application of the drug to a patient requiring it (Phase III), where satisfactory results have been also obtained, since the current patients who have been treated with the developed formulation are clinically assessed and shown a satisfactory response reflected in their normal heart activity. In such a manner, the PPF plasmatic concentrations in said patients have contributed to the control of the ailment, thereby showing effectiveness in the extemporaneous formulation, regarding arrhythmias control, wherein no side effects have been observed. The development of this type of formulations represents an alternative for administering said drug to children, given that there in no paediatric presentation currently available on t he market of said drug in Mexico.