Variability of Drugs with Narrow Therapeutic Window in Transplantology - Potential Costs and Clinical Consequences

2012 ◽  
Vol 26 (1) ◽  
Author(s):  
Paweł Szczudło ◽  
Marta Hreńczuk
Keyword(s):  
Therapeutic Window ◽  
Narrow Therapeutic Window ◽  
Clinical Consequences

The Nordic-HILUS Trial: Ultracentral Lung Stereotactic Ablative Radiotherapy and a Narrow Therapeutic Window

2021 ◽  
Vol 16 (10) ◽  
pp. e79-e80 ◽  
Author(s):  
Stephen A. Rosenberg ◽  
Raymond Mak ◽  
Rupesh Kotecha ◽  
Bill W. Loo ◽  
Suresh Senan
Keyword(s):  
Therapeutic Window ◽  
Stereotactic Ablative Radiotherapy ◽  
Narrow Therapeutic Window

scholarly journals Síndrome de Neurotoxicidade Irreversível Causada por Lítio

2017 ◽  
Vol 30 (2) ◽  
pp. 151
Author(s):  
Ana Luísa Silva ◽  
Carolina Ourique ◽  
Filipe Martins ◽  
Fernando Friões
Keyword(s):  
Therapeutic Range ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Serum Levels ◽  
Therapeutic Window ◽  
Narrow Therapeutic Window ◽  
Frequent Monitoring ◽  
Lithium Poisoning

Lithium has a narrow therapeutic window. Frequent monitoring of both serum levels and clinical signs of toxicity is warranted because toxicity may be present even when concentrations are within the therapeutic range. We report the case of a man with lithium poisoning, with persistent neurologic signs and symptoms even after removal of lithium from circulation – a diagnosis of syndrome of irreversible lithium-effectuated neurotoxicity (SILENT) was made.

Targeting NF-Kβ for the Prevention of Graft Versus Host Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3109-3109
Author(s):  
William R. Drobyski ◽  
Sanja Vodanovic-Jankovic ◽  
Parameswaran Hari ◽  
Paulette Jacobs ◽  
Richard Komorowski
Keyword(s):  
T Cells ◽  
Single Dose ◽  
Graft Versus Host Disease ◽  
Selective Inhibition ◽  
Early Mortality ◽  
Therapeutic Window ◽  
Host Disease ◽  
Graft Versus Host ◽  
Narrow Therapeutic Window ◽  
Tnf Α

Abstract NF-κB is a transcription factor that controls expression of a number of genes that are important for mediating immune and inflammatory responses, such as IL-1 and TNF-α , which are both overproduced during graft versus host disease (GVHD). To determine whether the NF-κB signaling pathway plays a role in the pathophysiology of GVHD, we examined the affect of bortezomib (PS-341, Velcade®), a proteasome inhibitor whose mechansism of action includes but is not limited to inhibition of NF-κB, and PS-1145, a IKB kinase (IKK) inhibitor that selectively inhibits NF-κB, on the induction of GVHD. Lethally irradiated C57BL/6 (H-2b) mice that were transplanted with MHC-incompatible B10.BR (H-2k) bone marrow (BM) and spleen cells and treated with a single dose of bortezomib (1 mg/kg) on the day of BMT had significantly prolonged survival compared to untreated GVHD controls (50% versus 0% survival at 60 days). In contrast, extended or delayed administration of this agent on a twice weekly schedule that recapitulated current clinical practice guidelines resulted in a significant increase in mortality as all animals died within ten days of transplantation. Histological analysis of bortezomib-treated mice demonstrated that mortality was attributable to severe pathological damage in the colon, indicating that there was a narrow therapeutic window within which bortezomib could be administered. Toxicity was GVHD-dependent as syngeneic marrow transplant recipients treated with a similar schedule for four weeks (8 doses) all survived for 60 days and had no evidence of pathological damage when compared to vehicle-treated controls. Given the narrow therapeutic window observed with bortezomib, we examined whether more selective inhibition of NF-κB with PS-1145 could prevent GVHD without inducing toxicity and early mortality. In vitro studies demonstrated that PS-1145 induced apoptosis in alloactivated T cells, similar to bortezomib, although a higher concentration was required for equivalent results (8 μM versus 0.32 μM). To achieve a serum concentration of PS-1145 necessary for the induction of T cell apoptosis in vivo, PS-1145 was administered at a dose of 50 mg/kg on days 0–2 post transplantation to recipients of MHC-incompatible marrow grafts. Treatment with PS-1145 resulted in similar GVHD protection when compared to animals administered a single dose of bortezomib. Prevention of GVHD by bortezomib and PS-1145 was associated with equivalent reductions of serum cytokine levels of IL-2, IL-10 and TNF-α when compared to GVHD controls. To determine whether the selective inhibition of NF-κB with PS-1145 caused less toxicity in BMT recipients, mice were administered this agent for 10 consecutive days beginning on the day of transplant. In contrast to results observed with bortezomib, PS-1145-treated mice had no early mortality and had superior survival when compared to GVHD controls (100% versus 0% survival at 60 days). GVHD protection in these mice was associated with significantly reduced expansion of alloreactive donor T cells in the spleen without compromise of donor engraftment. These results confirm a critical role for NF-κB in the pathophysiology of GVHD and indicate that selective inhibition of NF-κB may have a superior therapeutic index and constitute a viable approach to reduce GVHD.

scholarly journals The neurobehavioral benefit conferred by a single systemic administration of 8-OH-DPAT after brain trauma is confined to a narrow therapeutic window

2007 ◽  
Vol 416 (2) ◽  
pp. 165-168 ◽  
Author(s):  
Jeffrey P. Cheng ◽  
Haris A. Aslam ◽  
Ann N. Hoffman ◽  
Ross D. Zafonte ◽  
Anthony E. Kline
Keyword(s):  
Brain Trauma ◽  
Systemic Administration ◽  
Therapeutic Window ◽  
Narrow Therapeutic Window

scholarly journals Delayed recanalization in acute ischemic stroke patients: Late is better than never?

2019 ◽  
Vol 39 (12) ◽  
pp. 2536-2538 ◽  
Author(s):  
Jinwei Pang ◽  
John H Zhang ◽  
Yong Jiang
Keyword(s):  
Clinical Trials ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Brain Tissue ◽  
Symptom Onset ◽  
Therapeutic Window ◽  
Stroke Patients ◽  
Narrow Therapeutic Window ◽  
Better Than

Successful recanalization of the occluded vessel as early as possible has been widely accepted as the key principle of acute ischemic stroke (AIS) treatment. Unfortunately, for many years, the vast majority of AIS patients were prevented from receiving effective recanalization therapy because of a narrow therapeutic window. Recently, a series of inspiring clinical trials have indicated that more patients may benefit from delayed recanalization during an expanded therapeutic window, even up to 24 h after symptom onset. However, could potentially salvageable brain tissue (penumbra) in patients who do not receive medication within 24 h still possible to be saved?

Dysrhythmias Associated with Digoxin Toxicity

1992 ◽  
Vol 3 (1) ◽  
pp. 220-225
Author(s):  
Lynn A. Kelso
Keyword(s):  
Digoxin Toxicity ◽  
Therapeutic Window ◽  
Narrow Therapeutic Window ◽  
Life Threatening

Digoxin is frequently prescribed for patients. With a narrow therapeutic window, toxicity can quickly occur. Nurses must quickly recognize dysrhythmias associated with digoxin toxicity to prevent life-threatening situations

Alpha-momorcharin (α-MMC) exerts effective anti-human breast tumor activities but has a narrow therapeutic window in vivo

Fitoterapia ◽  
2015 ◽  
Vol 100 ◽  
pp. 139-149 ◽  
Author(s):  
Dongliang Cao ◽  
Yun Sun ◽  
Ling Wang ◽  
Qianchuan He ◽  
Juecun Zheng ◽  
...  
Keyword(s):  
Breast Tumor ◽  
Therapeutic Window ◽  
Human Breast ◽  
Human Breast Tumor ◽  
Narrow Therapeutic Window

Can pharmacogenetics help patients under chronic treatment with coumarin anticoagulants?

2016 ◽  
Vol 31 (4) ◽  
Author(s):  
Isabel López ◽  
Estela Sangüesa ◽  
Yves Vancraenendonck ◽  
Estefanía Zuriaga ◽  
María Pilar Ribate ◽  
...  
Keyword(s):  
Vitamin K ◽  
Chronic Treatment ◽  
Vitamin K Antagonists ◽  
Clinical Information ◽  
Individual Variability ◽  
Therapeutic Window ◽  
Antithrombotic Drugs ◽  
Stable Dose ◽  
Narrow Therapeutic Window ◽  
Risk Of Bleeding

Abstract Vitamin K antagonists are highly effective antithrombotic drugs. However, appropriate dosing is difficult to establish owing to its narrow therapeutic window as well as widespread inter- and intra-individual variability in dosage. Compared with dosing solely based on clinical information, pharmacogenetics can help improve the therapy with coumarins by decreasing the time to reach a stable dose and reducing the risk of bleeding. Most of the studies about genotyping of patients using vitamin K antagonists have focused on predicting the stable dose. Two genes have been shown to have the most influence on dosing:

Sign in / Sign up

Export Citation Format

Share Document