Search results for: fluvoxamine

Authors: Ana-Maria Gheldiu, Bianca M. Abrudan, Maria A. Neag, Laurian Vlase, Dana M. Muntean

Abstract:

Background information: The objective of this study was to investigate the effect of multiple-dose fluvoxamine on the pharmacokinetic profile of single-dose carvedilol in rats, in order to evaluate this possible drug-drug pharmacokinetic interaction. Methods: A preclinical study, in 28 white male Wistar rats, was conducted. Each rat was cannulated on the femoral vein, prior to being connected to BASi Culex ABC®. Carvedilol was orally administrated in rats (3.57 mg/kg body mass (b.m.)) in the absence of fluvoxamine or after a pre-treatment with multiple oral doses of fluvoxamine (14.28 mg/kg b.m.). The plasma concentrations of carvedilol were estimated by high performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters of carvedilol were analyzed by non-compartmental method. Results: After carvediol co-administration with fluvoxamine, an approximately 2-fold increase in the exposure of carvedilol was observed, considering the significantly elevated value of the total area under the concentration versus time curve (AUC₀₋∞). Moreover, an increase by approximately 145% of the peak plasma concentration was found, as well as an augmentation by approximately 230% of the half life time of carvedilol was observed. Conclusion: Fluvoxamine co-administration led to a significant alteration of carvedilol’s pharmacokinetic profile in rats, these effects could be explained by the existence of a drug-drug interaction mediated by CYP2D6 inhibition. Acknowledgement: This work was supported by CNCS Romania – project PNII-RU-TE-2014-4-0242.

Keywords: carvedilol, fluvoxamine, drug-drug pharmacokinetic interaction, rats

Procedia PDF Downloads 248

Authors: Salem Abdalla

Abstract:

Objective: Dipyrone is a widely used, well tolerated analgesic drug which, however, is compromised by agranulocytosis as an adverse effect. Subsequent to no enzymatic hydrolysis, the primary metabolic step is N-demethylation of 4-methylaminoantipyrine (4-MAA) to 4-aminoantipyrine (4-AA). The aim of the present study was to identify the cytochrome P-450 enzyme (CYP) mediating this reaction. Methods: We identified the relevant CYP using virus expressed isolated rat liver microsomes with chemical inhibition studies. The substrate of 4-methylaminantipyrine was employed at six different concentrations (25, 50, 100, 400, 800, and 1200 µmol/l) with varying concentrations of selective inhibitors of CYP1A2 (furafylline, fluvoxamine), CYP3A4 (ketoconazole), CYP2A6 (coumarin), CYP2D6 (quinidine), CYP2C19 (omeprazole, fluvoxamine, tranylcypromine), CYP2C9 (sulfaphenazole), and CYP1A1 (alpha-naphthoflavone). 4-MAA and 4-AA were analyzed by HPLC, and enzyme kinetic parameters (Km and Vmax) were determined by regression (Sigma plot 9.0). Results: The N-demethylation of 4-MAA by microsomes prepared from baculovirus-expressing human CYP was pronounced with CYP2C19. Intrinsic clearances of the most active enzymes were 0.092, 0.027, and 0.026 for the CYP enzymes 2C19, 2D6, and 1A2, respectively. Metabolism by rat liver microsomes was strongly inhibited by omeprazole (IC50 of 0.05). Conclusion: The enzyme CYP2C19 apparently has an important role in N-demethylation of 4-methylaminoantipyrine which should be further analyzed in clinical studies and which may also be interesting concerning the agranulocytosis.

Keywords: dipyrone, 4-methylaminoantipyrine (4-MAA), 4- aminoantipyrine (4-AA), metabolism, human CYP2C19

Procedia PDF Downloads 215

Authors: Azadeh Moghaddas, Mehrnoush Dianatkhah, Padideh Ghaeli

Abstract:

The main characteristics of borderline personality disorder (BPD) are instable regulation of affect and self-image, impulsive behavior, and lack of interpersonal relationships. Clinically, emotional dysregulation, impulsive aggression, repeated self-injury, and suicidal thought are noted with this disorder. Proper management of patients with BPD is a difficult challenge due to the complex features of this disorder. Pharmacotherapy of BPD in order to control impulsive behavior and to stabilize affect in patients with BPD has been receiving a lot of attention. Anticonvulsant agents such as topiramate, valproate, or lamotrigine, atypical antipsychotics such as aripiprazole and olanzapine and antidepressants such as monoamine oxidase inhibitors and selective serotonin reuptake inhibitors like fluvoxamine have been implicated in the treatment of BPD. Unfortunately, none of these medications can be used alone or even in combination as sole treatment of BPD. Medications may be used mostly to resolve or reduce impulsivity and aggression in these patients. Naltrexone (NTX), a nonspecific competitive opiate antagonist has been suggested, in the literature, to control self-injurious behavior (SIB) and dissociative symptoms in patients with BPD. This brief review has been intended to look at all documented evidence on the use of NTX in the management of BPD and to reach a comprehensive conclusion.

Keywords: borderline personality disorder, naltrexone, self-injurious behavior, dissociative symptoms

Procedia PDF Downloads 272