Extension de temps QT
Effets indésirables des médicaments
Variantes ✨Pour l'évaluation intensive en calcul des variantes, veuillez choisir l'abonnement standard payant.
Explications pour les patients
Nous n'avons aucun avertissement supplémentaire pour l'association de abirateron et de grepafloxacine. Veuillez également consulter les informations spécialisées pertinentes.
Les changements d'exposition mentionnés sont liés aux changements de la courbe concentration plasmatique en fonction du temps [ASC]. Nous ne prévoyons aucun changement d'exposition à la abirateron, lorsqu'il est combiné avec la grepafloxacine (100%). Nous n'avons détecté aucune modification de l'exposition à la grepafloxacine. Nous ne pouvons actuellement pas estimer l'influence de la abirateron.
Les paramètres pharmacocinétiques de la population moyenne sont utilisés comme point de départ pour calculer les changements individuels d'exposition dus aux interactions.
La abirateron a une biodisponibilité orale moyenne [ F ] de 50%, raison pour laquelle les concentrations plasmatiques maximales [Cmax] ont tendance à changer avec une interaction. La demi-vie terminale [ t12 ] est de 18 heures et les taux plasmatiques constants [ Css ] sont atteints après environ 9 999 heures. La liaison aux protéines [ Pb ] est très forte à 99.8% et le volume de distribution [ Vd ] est très important à 2815 litres, Le métabolisme s'effectue principalement via le CYP3A4.
La biodisponibilité de la grepafloxacine est inconnue. La liaison aux protéines [Pb] n'est pas connue. Le métabolisme a lieu via le CYP1A2 et le CYP3A4, entre autres et le transport actif se fait notamment via PGP.
|Les scores||∑ Points||abi||gre|
|Effets sérotoninergiques a||0||Ø||Ø|
Évaluation: Selon nos connaissances, ni la abirateron ni la grepafloxacine n'augmentent l'activité sérotoninergique.
|Les scores||∑ Points||abi||gre|
|Kiesel & Durán b||0||Ø||Ø|
Évaluation: Selon nos résultats, ni la abirateron ni la grepafloxacine n'augmentent l'activité anticholinergique.
Extension de temps QT
|Les scores||∑ Points||abi||gre|
Évaluation: En association, la abirateron et la grepafloxacine peuvent potentiellement déclencher des arythmies ventriculaires de type torsades de pointes.
Effets secondaires généraux
|Effets secondaires||∑ la fréquence||abi||gre|
|Œdème périphérique||20.0 %||20.0||n.a.|
|ALT élevé||13.0 %||13.0||n.a.|
|AST élevé||13.0 %||13.0||n.a.|
|Infection urinaire||10.0 %||10.0||n.a.|
|La diarrhée||5.5 %||5.5||n.a.|
|Fibrillation auriculaire||2.6 %||2.6||n.a.|
|Angine de poitrine||1.6 %||1.6||n.a.|
Sur la base de vos
Abstract: The purpose of this study was to clarify the contribution of P-glycoprotein to the bioavailability and intestinal secretion of grepafloxacin and levofloxacin in vivo. Plasma concentrations of grepafloxacin and levofloxacin after intravenous and intraintestinal administration were increased by cyclosporin A, a P-glycoprotein inhibitor, in rats. The total body clearance and volume of distribution at steady state of grepafloxacin were significantly decreased to 60 and 63% of the corresponding control values by cyclosporin A. The apparent oral clearance of grepafloxacin was decreased to 33% of the control, and the bioavailability of grepafloxacin was increased to 95% by cyclosporin A from 53% in the controls. Intestinal clearance of grepafloxacin and levofloxacin were decreased to one-half and one-third of the control, respectively, and biliary clearance of grepafloxacin was also decreased to one-third with cyclosporin A in rats. Intestinal secretion of grepafloxacin in mdr1a/1b (-/-) mice, which lack mdr1-type P-glycoproteins, was significantly decreased compared with wild-type mice, although the biliary secretion was similar. Intestinal secretion of grepafloxacin in wild-type mice treated with cyclosporin A was comparable to those in mdr1a/1b (-/-) mice with or without cyclosporin A, indicating that cyclosporin A completely inhibited P-glycoprotein-mediated intestinal transport of grepafloxacin. In conclusion, our results indicated that P-glycoprotein mediated the intestinal secretion of grepafloxacin and limited the bioavailability of this drug in vivo.
Abstract: The fluoroquinolone antibiotics sparfloxacin, grepafloxacin, gatifloxacin, and levofloxacin have been reported to cause torsades de pointes. Pre-existing risk factors increase vulnerability to this life-threatening arrhythmia. In a 65-year-old woman with a history of hypertension, coronary artery disease, systemic lupus erythematosus, and osteomyelitis, QTc interval prolongation (605 ms) and torsades de pointes developed after the initiation of levofloxacin, 250 mg intravenously once daily. The patient was hypokalemic and mildly hypomagnesemic before the initiation of levofloxacin and at the time of occurrence of torsades de pointes. The QTc interval decreased to 399 ms within hours of discontinuation of the levofloxacin, after which she had no further arrhythmias. In this and the majority of other published cases of fluoroquinolone-associated torsades de pointes, patients had at least 1 risk factor for the arrhythmia, and most had multiple risk factors. Fluoroquinolone antibiotics should be avoided whenever possible in patients with pre-existing risk factors for torsades de pointes.
Abstract: Three open-label, single-dose studies investigated the impact of hepatic or renal impairment on abiraterone acetate pharmacokinetics and safety/tolerability in non-cancer patients. Patients (n = 8 each group) with mild/moderate hepatic impairment or end-stage renal disease (ESRD), and age-, BMI-matched healthy controls received a single oral 1,000 mg abiraterone acetate (tablet dose); while patients (n = 8 each) with severe hepatic impairment and matched healthy controls received 125- and 2,000-mg abiraterone acetate (suspension doses), respectively (systemic exposure of abiraterone acetate suspension is approximately half to that of tablet formulation). Blood was sampled at specified timepoints up to 72 or 96 hours postdose to measure plasma abiraterone concentrations. Abiraterone exposure was comparable between healthy controls and patients with mild hepatic impairment or ESRD, but increased by 4-fold in patients with moderate hepatic impairment. Despite a 16-fold reduction in dose, abiraterone exposure in patients with severe hepatic impairment was about 22% and 44% of the Cmax and AUC∞ of healthy controls, respectively. These results suggest that abiraterone pharmacokinetics were not changed markedly in patients with ESRD or mild hepatic impairment. However, the capacity to eliminate abiraterone was substantially compromised in patients with moderate or severe hepatic impairment. A single-dose administration of abiraterone acetate was well-tolerated.
Abstract: Two novel oral drugs that target androgen signaling have recently become available for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Abiraterone acetate inhibits the synthesis of the natural ligands of the androgen receptor, whereas enzalutamide directly inhibits the androgen receptor by several mechanisms. Abiraterone acetate and enzalutamide appear to be equally effective for patients with mCRPC pre- and postchemotherapy. Rational decision making for either one of these drugs is therefore potentially driven by individual patient characteristics. In this review, an overview of the pharmacokinetic characteristics is given for both drugs and potential and proven drug-drug interactions are presented. Additionally, the effect of patient-related factors on drug disposition are summarized and the limited data on the exposure-response relationships are described. The most important pharmacological feature of enzalutamide that needs to be recognized is its capacity to induce several key enzymes in drug metabolism. The potency to cause drug-drug interactions needs to be addressed in patients who are treated with multiple drugs simultaneously. Abiraterone has a much smaller drug-drug interaction potential; however, it is poorly absorbed, which is affected by food intake, and a large interpatient variability in drug exposure is observed. Dose reductions of abiraterone or, alternatively, the selection of enzalutamide, should be considered in patients with hepatic dysfunction. Understanding the pharmacological characteristics and challenges of both drugs could facilitate decision making for either one of the drugs.
Abstract: We present a case of a 77 year-old gentleman with previous coronary artery bypass grafting, admitted to hospital with recurrent torsades de pointes (TdP) due to abiraterone-induced hypokalaemia and prolonged QTc. The patient was on abiraterone and prednisone for metastatic prostate cancer. He required multiple defibrillations for recurrent TdP. Abiraterone is a relatively novel drug used in metastatic prostate cancer and we discuss this potential adverse effect and its management in this unusual presentation.