Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Clin Pharm Ther ; 47(8): 1284-1292, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35504629

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Although predictable pharmacokinetic and pharmacodynamic of rivaroxaban allow fixed dosing regimens without routine coagulation monitoring, there is still the necessity to monitor and predict the effects of rivaroxaban in specific conditions and different populations. The current study was designed and conducted to analyze the rivaroxaban population pharmacokinetics in Iranian patients and establish a pharmacokinetic/pharmacodynamic model to predict the relationship between rivaroxaban concentration and its anticoagulant activity. METHODS: A sequential nonlinear mixed effect pharmacokinetic/pharmacodynamic modeling method was used to establish the relation between rivaroxaban concentration and anti-factor Xa activity, prothrombin time, and activated partial thromboplastin time (aPTT) as pharmacodynamic biomarkers in a population of sixty-nine Iranian patients under treatment with oral rivaroxaban. Rivaroxaban plasma concentration was quantified by a validated high-performance liquid chromatography-tandem mass spectrometry. RESULTS AND DISCUSSION: The typical population values (inter-individual variability%) of the oral volume of distribution and clearance for a one-compartment model were 61.2 L (21%) and 3.68 L·h-1 (61%), respectively. Creatinine clearance and Child-Turcotte-Pugh score were found to affect the clearance. A direct link linear structural model best fitted the data for both prothrombin time and aPTT. The baseline estimates of aPTT and prothrombin time in the population were 35.0 (15%) and 12.6 (2%) seconds, respectively. The slope of the relationship between apTT, prothrombin time, and rivaroxaban concentration was 0.033 (28%) and 0.018 (54%) s·ml·ng-1 , respectively. The selected model for anti-factor Xa activity consisted of a direct link inhibitory Emax model with Hill coefficient. The maximum level of inhibition (Emax ) was 4 IU·ml-1 . The concentration of rivaroxaban producing 50% of the maximum inhibitory effect (EC50 ) was 180 (24%) ng·ml-1 , and Hill coefficient (γ) was 1.44 (108%). No covariates showed a statistically significant effect on PT and activated partial thromboplastin time prolonging properties and anti-factor Xa activity. WHAT IS NEW AND CONCLUSION: Our results confirmed that pharmacokinetic/pharmacodynamic models similar to those of the other studies describe the relationship between the rivaroxaban concentration and its anticoagulant effect in Iranian patients. However, considerable differences were observed in the parameters of the pharmacodynamics-pharmacokinetic models with the results of other reports that can explain the unpredictable effects of rivaroxaban in some patients.


Assuntos
Inibidores do Fator Xa , Rivaroxabana , Anticoagulantes/farmacologia , Inibidores do Fator Xa/farmacologia , Humanos , Irã (Geográfico) , Morfolinas/farmacocinética , Tempo de Tromboplastina Parcial , Rivaroxabana/farmacologia , Tiofenos/farmacocinética
2.
ARYA Atheroscler ; 18(3): 1-9, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-36815957

RESUMO

BACKGROUND: Although intra-cardiac shocks are a lifesaving approach in patients with systolic heart failure (HF), the probable effective factors related to shock occurrence are less frequently recognized. We designed this study to assess the factors associated with inappropriate or appropriate implantable cardioverter-defibrillator (ICD) shocks in patients with non-ischemic cardiomyopathy (NICM). METHODS: Ninety-nine patients with NICM who implanted ICD were enrolled from March 2018 to September 2019 and followed up with a three-month interval for up to one year. Shock therapy was defined as either appropriate or inappropriate shock. The odds ratio (OR) of inappropriate shock occurrence was calculated with crude and different adjusted models. RESULTS: The mean age of the population at baseline was 51.9 ± 15.4 years (men: 71%). Baseline data revealed that patients with inappropriate shocks had higher heart rates (HR), worse New York Heart Association (NYHA) class, and anti-tachycardia pacing (ATP) as well as higher percentages of amiodarone usage compared to groups with appropriate or no shock [HR: 96.8 ± 27.8 vs. 79.8 ± 12.1 vs. 76.2 ± 17.6 beats per minute (bpm), P = 0.014; NYHA class IV: 85.7% vs. 74.1% vs. 63.4%, P = 0.041; ATP: 37.5% vs. 29% vs. 5%, P = 0.010; amiodarone usage: 37.5% vs. 25.8% vs. 5%, P = 0.23, respectively]. Further multiple-adjusted OR did not reveal any significant independent association between the aforementioned variables and inappropriate shock incidence. CONCLUSION: This study indicates no significant independent predisposing factor in the occurrence of inappropriate shocks among patients with NICM. Other studies are required in this regard.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...