||Almitrine, also called as Duxil, a diphenylmethylpiperazine derivative, is a respiratory stimulant by the ATC that improves ventilation/perfusion relationships.
1.Stability-indicating high performance liquid chromatographic determination of raubasine in its binary mixture with kinetic study of raubasine acid degradation.
El-Sayed MA1. Talanta. 2011 Jan 15;83(3):717-23. doi: 10.1016/j.talanta.2010.10.012. Epub 2010 Oct 14.
Stability-indicative determination of raubasine (RAB) in the presence of its degradate and its binary mixture with almitrine dismesylate (ALM) was investigated. The degradation product had been isolated, via acid-degradation, characterized and confirmed. Selective quantification of RAB and ALM in bulk form, pharmaceutical formulations and/or in the presence of RAB degradate was demonstrated. The analytical technique adopted for quantification was high performance liquid chromatography (HPLC). Separation was performed using a ZORBAX ODS column with a mobile phase consisting of acetonitrile+phosphate buffer pH 3.4 80:20 (v/v) with UV detection at 254 nm. The method showed high sensitivity with good linearity over the concentration range of 5-120 and 5-60 μg mL(-1) for RAB and ALM respectively. The HPLC method was used to study the kinetics of RAB acid degradation that was found to follow a first-order reaction. The activation energy could be estimated from the Arrhenius plot and it was found to be 18.
2.Almitrine fails to improve oxygenation during one-lung ventilation with sevoflurane anesthesia.
Bermejo S1, Gallart L2, Silva-Costa-Gomes T1, Vallès J1, Aguiló R3, Puig MM1. J Cardiothorac Vasc Anesth. 2014 Aug;28(4):919-24. doi: 10.1053/j.jvca.2013.03.019. Epub 2013 Sep 7.
OBJECTIVE: Almitrine enhances hypoxic pulmonary vasoconstriction (HPV) and can improve hypoxemia related to one-lung ventilation (OLV). Studies using almitrine have been conducted without inhaled anesthetics because they could inhibit HPV, counteracting the effect of almitrine. This hypothesis, however, has not been confirmed. This study's aim was to evaluate whether almitrine could improve oxygenation when administered during OLV with sevoflurane anesthesia.
3.Stability-indicating methods for the determination of a mixture of almitrine and raubasine by derivative spectrophotometry.
El-Sayed MA1. Drug Test Anal. 2009 Jun;1(6):279-85. doi: 10.1002/dta.48.
A second-derivative spectrophotometric method ((2)D) and a derivative ratio spectrum zero crossing ((1)DD) method were used to determine raubasine and almitrine dismesylate in the presence of raubasine degradation product, using methanol as a solvent. Linear relationships were obtained in the range from 6-20 microg ml(-1) raubasine for the ((2)D) method and 12-24 microg ml(-1) almitrine dismesylate for the ((1)DD) method. By applying these methods it was possible to determine raubasine in its pure powdered form with an accuracy of 99.93 +/- 1.116 (n = 8) for the ((2)D) method and almitrine dismesylate with an accuracy of 99.98 +/- 0.602 (n = 7) for the ((1)DD) method.Laboratory-prepared mixtures containing different ratios of raubasine, almitrine dismesylate and raubasine degradation product were analysed and the proposed methods were valid up to 50% of raubasine degradation product. They were found to be suitable stability-indicating assay methods for raubasine and almitrine dismesylate in pharmaceutical formulations.
4.Respiratory stimulant drugs in the post-operative setting.
Golder FJ1, Hewitt MM, McLeod JF. Respir Physiol Neurobiol. 2013 Nov 1;189(2):395-402. doi: 10.1016/j.resp.2013.06.010. Epub 2013 Jun 17.
Drug-induced respiratory depression (DIRD) is a common problem encountered post-operatively and can persist for days after surgery. It is not always possible to predict the timing or severity of DIRD due to the number of contributing factors. A safe and effective respiratory stimulant could improve patient care by avoiding the use of reversal agents (e.g., naloxone, which reverses analgesia as well as respiratory depression) thereby permitting better pain management by enabling the use of higher doses of analgesics, facilitate weaning from prolonged ventilation, and ameliorate sleep-disordered breathing peri-operatively. The purpose of this review is to discuss the current pharmaceutical armamentarium of drugs (doxapram and almitrine) that are licensed for use in humans as respiratory stimulants and that could be used to reverse drug-induced respiratory depression in the post-operative period. We also discuss new chemical entities (AMPAkines and GAL-021) that have been recently evaluated in Phase 1 clinical trials and where the initial regulatory registration would be as a respiratory stimulant.