scholarly journals Pharmacokinetics of Diclofenac and Hydroxypropyl-β-Cyclodextrin (HPβCD) Following Administration of Injectable HPβCD-Diclofenac in Subjects With Mild to Moderate Renal Insufficiency or Mild Hepatic Impairment

2017 ◽  
Vol 7 (2) ◽  
pp. 110-122 ◽  
Author(s):  
Douglas A. Hamilton ◽  
Cynthia C. Ernst ◽  
William G. Kramer ◽  
Donna Madden ◽  
Eric Lang ◽  
...  
Keyword(s):  
Renal Insufficiency ◽  
Hepatic Impairment ◽  
Mild Hepatic Impairment ◽  
Moderate Renal Insufficiency

scholarly journals Benefits and Safety of Tirofiban Among Acute Coronary Syndrome Patients With Mild to Moderate Renal Insufficiency

Circulation ◽  
2002 ◽  
Vol 105 (20) ◽  
pp. 2361-2366 ◽  
Author(s):  
James L. Januzzi ◽  
Steven M. Snapinn ◽  
Peter M. DiBattiste ◽  
Ik-Kyung Jang ◽  
Pierre Theroux
Keyword(s):  
Acute Coronary Syndrome ◽  
Renal Insufficiency ◽  
Coronary Syndrome ◽  
Moderate Renal Insufficiency

scholarly journals Single-dose pharmacokinetics of BMS-986177/JNJ-70033093 in participants with mild or moderate hepatic impairment compared to healthy participants

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Perera ◽  
G Abelian ◽  
D Li ◽  
Z Wang ◽  
L Zhang ◽  
...  
Keyword(s):  
Single Dose ◽  
Hepatic Impairment ◽  
Hepatic Function ◽  
Moderate Hepatic Impairment ◽  
Funding Source ◽  
Antithrombotic Agents ◽  
Normal Hepatic Function ◽  
Pugh Class ◽  
Healthy Participants ◽  
Mild Hepatic Impairment

Abstract Background According to the scientific evidence accumulated to date (ie, genetic, epidemiological, preclinical, clinical), the modulation of Factor XI (FXI) function may provide a novel mechanism for systemic anticoagulation without increasing the risk of clinically significant bleeding in a variety of conditions predisposing patients to a high risk of thrombotic or bleeding events. BMS-986177/JNJ-70033093 (BMS-177/JNJ-3093) is a small molecule that inhibits the active form of FXI (FXIa) with high affinity and selectivity. Depending on the indication, BMS-177/JNJ-3093 may provide benefit to patients as add-on or potentially replacement therapy to the current standard of care antithrombotic agents. Patients with hepatic impairment may have an increased risk of bleeding when using existing antithrombotic agents and therefore may benefit from drugs with an improved safety profile. Purpose To assess the effect of mild or moderate hepatic impairment on the pharmacokinetic (PK) properties of BMS-177/JNJ-3093. Methods This was a multicenter, open-label, non-randomized, single-dose study. A single 60-mg oral dose of BMS-177/JNJ-3093 was administered to 9 participants with mild hepatic impairment (Child-Pugh class A), 8 participants with moderate hepatic impairment (Child-Pugh class B), and 9 healthy participants with normal hepatic function. Healthy participants were matched to participants with hepatic impairment in each Child-Pugh class with regard to body weight. To assess the effects of hepatic impairment on BMS-177/JNJ-3093 PK, an analysis of variance was performed on the natural log-transformed Cmax, AUC(INF), and AUC(0-T) with hepatic function group as a fixed effect. Results BMS-177/JNJ-3093 was well tolerated when administered as an oral dose of 60 mg in participants with mild or moderate hepatic impairment and healthy participants with normal hepatic function. There were no deaths, serious adverse events (AEs), severe AEs, bleeding AEs, or discontinuations due to an AE reported during the study. The geometric mean ratios (GMRs) (90% CI) comparing mild hepatic impairment to normal hepatic function were 1.180 (0.735, 1.895) and 1.168 (0.725, 1.882) for total BMS-177/JNJ-3093 maximum concentration (Cmax) and area under the curve from time 0 to infinity (AUC(INF)), respectively. The GMRs (90% CI) comparing moderate hepatic impairment to normal hepatic function were 1.140 (0.699, 1.857) and 0.996 (0.609, 1.628) for total BMS-177/JNJ-3093 Cmax and AUC(INF), respectively. Overall, levels of activated partial thromboplastin time (aPTT) increased in an exposure-related manner following single oral doses of 60 mg BMS-177/JNJ-3093 in all groups. Conclusion BMS-177/JNJ-3093 was well tolerated in the normal healthy participants and those with mild or moderate hepatic impairment. The observed changes indicate that a dose adjustment in these populations may not be necessary. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This work was sponsored by Bristol-Myers Squibb and Janssen Research & Development, LLC

scholarly journals Inflammation as a Mediator of the Link between Mild to Moderate Renal Insufficiency and Endothelial Dysfunction in Essential Hypertension

2006 ◽  
Vol 17 (4 suppl 2) ◽  
pp. S64-S68 ◽  
Author(s):  
Carmine Zoccali ◽  
Raffaele Maio ◽  
Giovanni Tripepi ◽  
Francesca Mallamaci ◽  
Francesco Perticone
Keyword(s):  
Essential Hypertension ◽  
Endothelial Dysfunction ◽  
Renal Insufficiency ◽  
Moderate Renal Insufficiency

Efficacy and Bleeding Risk of Newer Anticoagulants Compared to Conventional Treatment in Patients with Chronic Kidney Disease- a Meta-Analysis of Randomized Controlled Trials

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2325-2325
Author(s):  
Srinath Sundararajan ◽  
Mugilan Poongkunran ◽  
Chithra Poongkunran ◽  
Arun Kannan ◽  
Saravananan Balamuthusamy
Keyword(s):  
Renal Insufficiency ◽  
Odds Ratio ◽  
Conventional Treatment ◽  
Meta Analysis ◽  
Bleeding Risk ◽  
Arterial Embolism ◽  
Severe Renal Insufficiency ◽  
Newer Anticoagulants ◽  
Moderate Renal Insufficiency ◽  
Mild Renal Insufficiency

Abstract Background Multiple newer oral anticoagulants (NOAC) are currently approved for the prevention, treatment of venous thromboembolism (VTE) and prevention of stoke in atrial fibrillation (AF). Most of the clinical trials with NOAC have excluded patients with severe renal insufficiency. There is a paucity of safety and efficacy data of NOAC in comparison with conventional treatment (CT) in patients with mild or moderate renal impairment. We performed a meta-analysis of the randomized control trials (RCTs) comparing NOAC to CT in patients with renal insufficiency to understand the safety and efficacy of NACs. Methods Medline, PubMed, EMBASE, EBSCO, CINAHL and Cochrane databases were queried with the keywords - "newer anticoagulants", "renal insufficiency", "dabigatran", "rivaroxaban", "apixaban", and "edoxaban". RCTs comparing NOAC to CT (warfarin, low molecular weight heparin, heparin, aspirin or placebo) were included. Non-randomized single arm trials were excluded. Authors of RCTs with missing pertinent data were contacted through electronic mail. The safety end point analyzed was clinically significant or major bleeding risk. The efficacy end points analyzed were incidence of arterial embolism in AF studies and venous thromboembolism in VTE studies. European Medical Agency classification of renal insufficiency was used, with mild renal insufficiency defined as estimated glomerular filtration rate (eGFR) from 50 to 79 and moderate renal insufficiency defined as eGFR of 30 to 49 and severe renal insufficiency defined as eGFR< 30. Results Sixteen RCTs with 115,147 patients fulfilled our inclusion criteria. Rivoroxaban, apixaban, edoxaban and dabigatran were the newer anticoagulants used in these 16 RCTs. Among these, 48,403 patients had either mild or moderate renal insufficiency. Patients with mild renal insufficiency treated with NAOC had lower bleeding risk [Odds ratio 0.81(CI 0.72-0.90) p<0.0001], lower incidence of arterial thromboembolism [Odds ratio 0.74(CI 0.64-0.85) p<0.0001] compared to conventional treatment. Patients with moderate renal insufficiency treated with NAOC had lower incidence of arterial thromboembolism [Odds ratio 0.74(CI 0.62-0.89) p=0.001] and a trend towards lower bleeding risk [Odds ratio 0.89(CI 0.66-1.18) p=0.41], compared to conventional treatment. Also, a trend of lowered VTE incidence was observed with NOAC compared to conventional treatment in patients with mild [Odds ratio 0.70(CI 0.46 to 1.070) p=0.1] as well moderate [Odds ratio 0.69(CI 0.34 to 1.41) p=0.31] renal insufficiency. Conclusion: Newer anticoagulants have decreased odds for VTE, arterial embolism and bleeding in patients with mild to moderate renal insufficiency compared to conventional treatment. Disclosures No relevant conflicts of interest to declare.

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