China
Africa
Explore chapters and articles related to this topic
Ketoconazole
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Ketoconazole inhibits the metabolism of terfenadine (a non-sedating antihistamine), which normally undergoes extensive first-pass metabolism to two metabolites. When these drugs are co-administered, the resulting high plasma levels of unchanged terfenadine cause a prolongation of the QT interval on the electrocardiogram (Matthews et al., 1991). Combined administration of ketoconazole with fexofenadine, the active metabolite of terfenadine, significantly increases the area under the plasma concentration–time curve of fexofenadine by threefold (Ogasawara et al., 2007). However, ketoconazole failed to significantly prolong QT interval when co-administered with fexofenadine (Pratt et al., 1999). Prolongation of the QT interval is associated with a form of ventricular tachycardia called torsades de pointes, which requires different therapy than other forms of ventricular tachycardia. This syndrome has been reported in patients receiving both ketoconazole and terfenadine (Monahan et al., 1990), and the electrocardiographic repolarization abnormalities have been confirmed in a study by Honig et al. (1993). Although ketoconazole causes a significant increase in peak plasma loratidine levels as well as an increase in plasma levels of the active metabolite of loratidine, no changes in the QT interval have also been reported. The co-administration of ketoconazole and terfenadine is contraindicated. Torsades de pointes and prolonged QT interval have also been reported after the concomitant administration of ketoconazole and cisapride. Therefore, this combination is contraindicated. Co-administration of ketoconazole and domperidone is also contraindicated for the same reason. However, it has been demonstrated that concurrent administration of 200 mg ketoconazole twice daily with cinitapride, a prokinetic agent, has no effect on QT interval (Robert et al., 2007). Ketoconazole alone at therapeutic doses may prolong the QT interval and induce torsades de pointes without a concurrent use of QT interval–prolonging agents (Mok et al., 2005).
Pharmacokinetics and tolerability of cinitapride in healthy Chinese volunteers: a randomized, open-label, single- and multiple-dose study
Published in Xenobiotica, 2019
Xiong Zhang, Ying Wang, Junlin Cheng, Yunfang Hu, Jianghui Liu, Jing Chen, Xingye Yang, Hongwei Fan
Cinitapride (4-amino-N-[1-(3-cyclohexen-1-yl-methyl)-4-piperidinyl]-2-ethoxy-5-nitrobenzamide) is a gastrointestinal stimulant with prokinetic activity developed and marketed in Spain and Mexico by Almirall, S.A. (Marquez et al., 2011). Cinitapride has three pronged mechanisms of action; it acts as an agonist at 5HT4 serotonergic receptor and antagonists at 5HT2 serotonergic and D2 dopaminergic receptors (Hemalatha et al., 2013). Its therapeutic properties lie in its capacity to increase the tone of the lower esophageal sphincter concomitantly with a potent gastrokinetic effect, producing significant evacuation of the bowel (Demoly & Hillaire-Buys, 2004). In addition to this, CIN also reduces anterograde esophageal movements, consequently decreasing gastroesophageal reflux episodes (Portincasa et al., 2009). Cinitapride has shown to accelerate gastric emptying in both human and animals and has been effective in the treatment of dyspepsia and gastroesophageal reflux disease (Du et al., 2014). Based on these, CIN has been approved for use since 1990 in Spain, Latin America and most recently, in Asia for the treatment of gastroesophageal reflux, irritable bowel syndrome, and functional dyspepsia (Baqai et al., 2013; Du et al., 2014).
Current and emerging therapeutic options for the management of functional dyspepsia
Published in Expert Opinion on Pharmacotherapy, 2020
A. Vandenberghe, J. Schol, K. Van den Houte, I. Masuy, F. Carbone, J. Tack
Cinitapride is a 5-HT1 and 5-HT4 receptor agonist, and, a 5-HT2 antagonist, indicated for treatment of reflux disease, non-ulcer dyspepsia and delayed gastric emptying. In a controlled study with domperidone as active comparator, cinitapride had similar efficacy and was well tolerated [43]. The drug is free of QT segment prolongation [44,45]. Cinitapride is available in India, Pakistan, Peru, Argentina, Spain, Paraguay, Ecuador, Uruguay, and Mexico. A combination preparation of cinitapride and pantoprazole is available in some countries.