Résumé
98%
|
Pharmacocinétique
|
0% | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Alfuzosin | |||||||||||
| Les scores | -1% | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Extension de temps QT
| |||||||||||
|
Effets anticholinergiques
| |||||||||||
|
Effets sérotoninergiques
| |||||||||||
|
Effets indésirables des médicaments
|
-1% | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Vertiges | |||||||||||
| Mal de crâne | |||||||||||
| Infection respiratoire supérieure | |||||||||||
Variantes ✨
Pour l'évaluation intensive en calcul des variantes, veuillez choisir l'abonnement standard payant.
Zone d'application
L'alfuzosine est utilisée pour traiter les symptômes de l'hyperplasie bénigne de la prostate (HBP). Il est pris par voie orale sous forme de comprimé à libération prolongée. L'alfuzosine est un ingrédient actif du groupe des alpha-bloquants. En occupant le récepteur adrénergique α1, il bloque l'action de l'adrénaline (antagonisme compétitif). Cela détend les muscles de l'urètre et de la prostate, augmente le flux d'urine et facilite la miction. Cependant, la taille de la prostate n'est pas affectée. Les récepteurs adrénergiques Α1B sont également occupés dans le système vasculaire, ce qui peut entraîner une baisse de la pression artérielle.
Pharmacocinétique
-0%
| ∑ Expositiona | alf | |
|---|---|---|
| Alfuzosin | 1 |
Symbole (a): changement multiplié par X de l'AUC
Légende (n.a.): Information non disponible
Légende (n.a.): Information non disponible
Étant donné que seule la alfuzosin a été introduite sans autre substance, aucune interaction pharmacocinétique ne peut être détectée.
Évaluation:
Les paramètres pharmacocinétiques de la population moyenne sont utilisés comme point de départ pour calculer les changements individuels d'exposition dus aux interactions.
La alfuzosin a une biodisponibilité orale moyenne [ F ] de 49%, raison pour laquelle les concentrations plasmatiques maximales [Cmax] ont tendance à changer avec une interaction. La demi-vie terminale [ t12 ] est de 9.55 heures et les taux plasmatiques constants [ Css ] sont atteints après environ 9 999 heures. La liaison aux protéines [ Pb ] est modérément forte à 86% et le volume de distribution [ Vd ] est très important à 224 litres, Étant donné que la substance a un faible taux d'extraction hépatique de 0,9, le déplacement de la liaison aux protéines [Pb] dans le contexte d'une interaction peut augmenter l'exposition. Le métabolisme s'effectue principalement via le CYP3A4.
Effets sérotoninergiques
-0%
| Les scores | ∑ Points | alf |
|---|---|---|
| Effets sérotoninergiques a | 0 | Ø |
Symbole (a): Augmentation du risque de 5 points.
Évaluation: Selon nos connaissances, la alfuzosin n'augmente pas l'activité sérotoninergique.
Effets anticholinergiques
-0%
| Les scores | ∑ Points | alf |
|---|---|---|
| Kiesel b | 0 | Ø |
Symbole (b): Risque accru de 3 points.
Évaluation: Selon nos résultats, la alfuzosin n'augmente pas l'activité anticholinergique.
Extension de temps QT
-1%
| Les scores | ∑ Points | alf |
|---|---|---|
| RISK-PATH c | 0.5 | ++ |
Symbole (c): Augmentation du risque de 10 points.
La alfuzosin peut potentiellement augmenter le temps QT, mais nous ne connaissons pas les arythmies des torsades de pointes.
Effets secondaires généraux
-1%
| Effets secondaires | ∑ la fréquence | alf |
|---|---|---|
| Vertiges | 5.7 % | 5.7 |
| Mal de crâne | 3.0 % | 3.0 |
| Infection respiratoire supérieure | 3.0 % | 3.0 |
| Fatigue | 2.7 % | 2.7 |
| Douleur abdominale | 1.0 % | + |
| La nausée | 1.0 % | + |
| Hypotension orthostatique | 0.4 % | 0.4 |
| Syncope | 0.2 % | 0.2 |
| Tachycardie | 0.0 % | 0.1 |
| Syndrome de l'iris disquette peropératoire | 0.0 % | 0.0 |
Extrait tabulaire des effets secondaires les plus courants
Signe (+): effet secondaire décrit, mais fréquence indéterminée
Signe (↑/↓): fréquence plutôt supérieure / inférieure en raison de l'exposition
Signe (+): effet secondaire décrit, mais fréquence indéterminée
Signe (↑/↓): fréquence plutôt supérieure / inférieure en raison de l'exposition
Système reproducteur
Priapisme: alfuzosin
Limites
Sur la base de vos
Références bibliographiques
Authors: Salva P Bianchetti G Morselli P Garcia-Teresa G Costa J
Abstract: The aim of this study was to assess the linearity of pharmacokinetic of alfuzosin, administered by oral route, at the doses of 1, 2.5, and 5 mg to 12 young healthy volunteers. The pharmacokinetic parameters (tmax, Cmax, AUC, t1/2 beta) obtained from plasma alfuzosin concentrations after administration of the three doses show that pharmacokinetics of alfuzosin is linear in the range of doses 1-5 mg. Mean pharmacokinetic parameters of alfuzosin observed after 1, 2.5, and 5 mg were, respectively: tmax (h) 1.5 +/- 0.3, 1.1 +/- 0.2, 1.3 +/- 0.1; Cmax (ng ml-1) 2.6 +/- 0.3, 9.4 +/- 1.2, 13.5 +/- 1.0; AUC (ng ml-1 h) 17.7 +/- 2.9, 51.7 +/- 7.1, 99.0 +/- 14.1; t1/2 (h) 3.7 +/- 0.4, 3.9 +/- 0.2, 3.8 +/- 0.3. Cmax (corrected by the dose) obtained after 2.5 mg was significantly higher than those obtained after 1 and 5 mg. This difference seems to be due principally to the intraindividual variability. The absence of statistically significant difference on individual values of AUC corrected by the administered dose, supports the linearity of the pharmacokinetics of alfuzosin in the range of doses between 1 and 5 mg. Some postural hypotension, clinical criterion, was observed with a frequency increasing with the dose in these healthy subjects: 0 volunteers of 12 after 1 mg, 3 volunteers of 12 after 2.5 mg and 4 volunteers of 12 after 5 mg.
Pubmed Id: 1358243
Abstract: The aim of this study was to assess the linearity of pharmacokinetic of alfuzosin, administered by oral route, at the doses of 1, 2.5, and 5 mg to 12 young healthy volunteers. The pharmacokinetic parameters (tmax, Cmax, AUC, t1/2 beta) obtained from plasma alfuzosin concentrations after administration of the three doses show that pharmacokinetics of alfuzosin is linear in the range of doses 1-5 mg. Mean pharmacokinetic parameters of alfuzosin observed after 1, 2.5, and 5 mg were, respectively: tmax (h) 1.5 +/- 0.3, 1.1 +/- 0.2, 1.3 +/- 0.1; Cmax (ng ml-1) 2.6 +/- 0.3, 9.4 +/- 1.2, 13.5 +/- 1.0; AUC (ng ml-1 h) 17.7 +/- 2.9, 51.7 +/- 7.1, 99.0 +/- 14.1; t1/2 (h) 3.7 +/- 0.4, 3.9 +/- 0.2, 3.8 +/- 0.3. Cmax (corrected by the dose) obtained after 2.5 mg was significantly higher than those obtained after 1 and 5 mg. This difference seems to be due principally to the intraindividual variability. The absence of statistically significant difference on individual values of AUC corrected by the administered dose, supports the linearity of the pharmacokinetics of alfuzosin in the range of doses between 1 and 5 mg. Some postural hypotension, clinical criterion, was observed with a frequency increasing with the dose in these healthy subjects: 0 volunteers of 12 after 1 mg, 3 volunteers of 12 after 2.5 mg and 4 volunteers of 12 after 5 mg.
Authors: Marbury TC Blum RA Rauch C Pinquier JL
Abstract: The effect of renal impairment on the safety and pharmacokinetics of a once-daily formulation of alfuzosin, 10 mg, was evaluated. In an open, single-dose study, 26 volunteers, ages 18 to 65 years, were classified as having normal renal function (n = 8) or mild (n = 6), moderate (n = 6), or severe (n = 6) renal impairment. Mean Cmax values increased by a factor of 1.20, 1.52, and 1.20 in subjects with mild, moderate, or severe renal impairment, respectively, compared with controls. Values for AUC(0-infinity) were 1.46, 1.47, and 1.44, respectively. The t(1/2z) was increased only in the group with severe renal impairment. Emergent vasodilatory adverse events were reported by 4 of 26 subjects. No discontinuations due to adverse events occurred. Laboratory parameters were satisfactory in all groups. In conclusion, once-daily alfuzosin, 10 mg, could be safely administered to patients with impaired renal function, and dosage adjustment does not seem necessary.
Pubmed Id: 12463725
Abstract: The effect of renal impairment on the safety and pharmacokinetics of a once-daily formulation of alfuzosin, 10 mg, was evaluated. In an open, single-dose study, 26 volunteers, ages 18 to 65 years, were classified as having normal renal function (n = 8) or mild (n = 6), moderate (n = 6), or severe (n = 6) renal impairment. Mean Cmax values increased by a factor of 1.20, 1.52, and 1.20 in subjects with mild, moderate, or severe renal impairment, respectively, compared with controls. Values for AUC(0-infinity) were 1.46, 1.47, and 1.44, respectively. The t(1/2z) was increased only in the group with severe renal impairment. Emergent vasodilatory adverse events were reported by 4 of 26 subjects. No discontinuations due to adverse events occurred. Laboratory parameters were satisfactory in all groups. In conclusion, once-daily alfuzosin, 10 mg, could be safely administered to patients with impaired renal function, and dosage adjustment does not seem necessary.
Authors: Extramiana F Maison-Blanche P Cabanis MJ Ortemann-Renon C Beaufils P Leenhardt A
Abstract: BACKGROUND: The formulas for heart rate (HR) correction of QT interval have been shown to overcorrect or undercorrect this interval with changes in HR. A Holter-monitoring method avoiding the need for any correction formulas is proposed as a means to assess drug-induced QT interval changes. METHODS: A thorough QT study included 2 single doses of the alpha1-adrenergic receptor blocker alfuzosin, placebo, and a QT-positive control arm (moxifloxacin) in 48 healthy subjects. Bazett, Fridericia, population-specific (QTcN), and subject-specific (QTcNi) correction formulas were applied to 12-lead electrocardio-graphic recording data. QT1000 (QT at RR = 1000 ms), QT largest bin (at the largest sample size bin), and QT average (average QT of all RR bins) were obtained from Holter recordings by use of custom software to perform rate-independent QT analysis. RESULTS: The 3 Holter end points provided similar results, as follows: Moxifloxacin-induced QT prolongation was 7.0 ms (95% confidence interval [CI], 4.4-9.6 ms) for QT1000, 6.9 ms (95% CI, 4.8-9.1 ms) for QT largest bin, and 6.6 ms (95% CI, 4.6-8.6 ms) for QT average. At the therapeutic dose (10 mg), alfuzosin did not induce significant change in the QT. The 40-mg dose of alfuzosin increased HR by 3.7 beats/min and induced a small QT1000 increase of 2.9 ms (95% CI, 0.3-5.5 ms) (QTcN, +4.6 ms [95% CI, 2.1-7.0 ms]; QTcNi, +4.7 ms [95% CI, 2.2-7.1 ms]). Data corrected by "universal" correction formulas still showed rate dependency and yielded larger QTc change estimations. The Holter method was able to show the drug-induced changes in QT rate dependence. CONCLUSIONS: The direct Holter-based QT interval measurement method provides an alternative approach to measure rate-independent estimates of QT interval changes during treatment.
Pubmed Id: 15903123
Abstract: BACKGROUND: The formulas for heart rate (HR) correction of QT interval have been shown to overcorrect or undercorrect this interval with changes in HR. A Holter-monitoring method avoiding the need for any correction formulas is proposed as a means to assess drug-induced QT interval changes. METHODS: A thorough QT study included 2 single doses of the alpha1-adrenergic receptor blocker alfuzosin, placebo, and a QT-positive control arm (moxifloxacin) in 48 healthy subjects. Bazett, Fridericia, population-specific (QTcN), and subject-specific (QTcNi) correction formulas were applied to 12-lead electrocardio-graphic recording data. QT1000 (QT at RR = 1000 ms), QT largest bin (at the largest sample size bin), and QT average (average QT of all RR bins) were obtained from Holter recordings by use of custom software to perform rate-independent QT analysis. RESULTS: The 3 Holter end points provided similar results, as follows: Moxifloxacin-induced QT prolongation was 7.0 ms (95% confidence interval [CI], 4.4-9.6 ms) for QT1000, 6.9 ms (95% CI, 4.8-9.1 ms) for QT largest bin, and 6.6 ms (95% CI, 4.6-8.6 ms) for QT average. At the therapeutic dose (10 mg), alfuzosin did not induce significant change in the QT. The 40-mg dose of alfuzosin increased HR by 3.7 beats/min and induced a small QT1000 increase of 2.9 ms (95% CI, 0.3-5.5 ms) (QTcN, +4.6 ms [95% CI, 2.1-7.0 ms]; QTcNi, +4.7 ms [95% CI, 2.2-7.1 ms]). Data corrected by "universal" correction formulas still showed rate dependency and yielded larger QTc change estimations. The Holter method was able to show the drug-induced changes in QT rate dependence. CONCLUSIONS: The direct Holter-based QT interval measurement method provides an alternative approach to measure rate-independent estimates of QT interval changes during treatment.
