V08 Pharmacology of enflicoxib, a new coxib drug: dose determination by efficacy and pharmacokinetic guided approach for the treatment of osteoarthritis in dogs based on an acute arthritis induction model

2021 ◽  
Author(s):  
C M Cendrós ◽  
M Salichs ◽  
A K Samp ◽  
G Encina ◽  
J M Vela ◽  
...  
Keyword(s):  
Drug Dose ◽  
Arthritis Induction ◽  
Acute Arthritis ◽  
Dose Determination ◽  
Induction Model

scholarly journals Titration Design: An Important Key in Drug Dose Determination

2019 ◽  
Vol 9 (4-s) ◽  
pp. 826-828
Author(s):  
Rada Santosh Kumar ◽  
R Venkata Sandhya
Keyword(s):  
Clinical Trials ◽  
Study Design ◽  
Dose Range ◽  
Drug Dose ◽  
Cumulative Effects ◽  
Optimum Dose ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Dose Determination ◽  
Type Study

Drug titration is the process of adjusting the dose of a medicine for the maximum benefits without adverse effects. To determine the optimum dose range the clinical trials are carried out and it is divided into two types of study design. The parallel type study design and titration type study design. The titration studies provide the information about the cumulative effects of the drug. Titration designs are mainly used in dose determining especially in insulin, anticonvulsants, anti-depressants, and sedatives. In the analysis of titration design, the phase I, II, III clinical trials are carried out to determine the dose-response relationship, safety and efficacy of the drug.

scholarly journals Implementation of pharmacogenomic testing in oncology care (PhOCus): study protocol of a pragmatic, randomized clinical trial

2020 ◽  
Vol 12 ◽  
pp. 175883592097411
Author(s):  
Natalie Reizine ◽  
Everett E. Vokes ◽  
Ping Liu ◽  
Tien M. Truong ◽  
Rita Nanda ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Drug Effects ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Clinical Decision ◽  
Drug Dose ◽  
Patient Specific ◽  
Drug Dosing ◽  
Patient Reported ◽  
Dose Modifications

Background: Many cancer patients who receive chemotherapy experience adverse drug effects. Pharmacogenomics (PGx) has promise to personalize chemotherapy drug dosing to maximize efficacy and safety. Fluoropyrimidines and irinotecan have well-known germline PGx associations. At our institution, we have delivered PGx clinical decision support (CDS) based on preemptively obtained genotyping results for a large number of non-oncology medications since 2012, but have not previously evaluated the utility of this strategy for patients initiating anti-cancer regimens. We hypothesize that providing oncologists with preemptive germline PGx information along with CDS will enable individualized dosing decisions and result in improved patient outcomes. Methods: Patients with oncologic malignancies for whom fluoropyrimidine and/or irinotecan-inclusive therapy is being planned will be enrolled and randomly assigned to PGx and control arms. Patients will be genotyped in a clinical laboratory across panels that include actionable variants in UGT1A1 and DPYD. For PGx arm patients, treating providers will be given access to the patient-specific PGx results with CDS prior to treatment initiation. In the control arm, genotyping will be deferred, and dosing will occur as per usual care. Co-primary endpoints are dose intensity deviation rate (the proportion of patients receiving dose modifications during the first treatment cycle), and grade ⩾3 treatment-related toxicities throughout the treatment course. Additional study endpoints will include cumulative drug dose intensity, progression-free survival, dosing of additional PGx supportive medications, and patient-reported quality of life and understanding of PGx. Discussion: Providing a platform of integrated germline PGx information may promote personalized chemotherapy dosing decisions and establish a new model of care to optimize oncology treatment planning.

scholarly journals Prescribing Errors With Direct Oral Anticoagulants and Their Impact on the Risk of Bleeding in Patients With Atrial Fibrillation

2021 ◽  
pp. 107424842110196
Author(s):  
Bruria Hirsh Raccah, PharmD, PhD ◽  
Yevgeni Erlichman ◽  
Arthur Pollak ◽  
Ilan Matok ◽  
Mordechai Muszkat
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Negative Impact ◽  
Conditional Logistic Regression ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Drug Dose ◽  
Prescribing Errors ◽  
Duration Of Treatment ◽  
Inappropriate Treatment

Introduction: Anticoagulants are associated with significant harm when used in error, but there are limited data on potential harm of inappropriate treatment with direct oral anticoagulants (DOACs). We conducted a matched case-control study among atrial fibrillation (AF) patients admitting the hospital with a chronic treatment with DOACs, in order to assess factors associated with the risk of major bleeding. Methods: Patient data were documented using hospital’s computerized provider order entry system. Patients identified with major bleeding were defined as cases and were matched with controls based on the duration of treatment with DOACs and number of chronic medications. Appropriateness of prescribing was assessed based on the relevant clinical guidelines. Conditional logistic regression was used to evaluate the potential impact of safety-relevant prescribing errors with DOACs on major bleeding. Results: A total number of 509 eligible admissions were detected during the study period, including 64 cases of major bleeding and 445 controls. The prevalence of prescribing errors with DOACs was 33%. Most prevalent prescribing errors with DOACs were “drug dose too low” (16%) and “non-recommended combination of drugs” (11%). Safety-relevant prescribing errors with DOACs were associated with major bleeding [adjusted odds ratio (aOR) 2.17, 95% confidence interval (CI) 1.14-4.12]. Conclusion: Prescribers should be aware of the potential negative impact of prescribing errors with DOACs and understand the importance of proper prescribing and regular follow-up.

scholarly journals Different Microfluidic Environments for In Vitro Testing of Lipid Nanoparticles against Osteosarcoma

2021 ◽  
Vol 8 (6) ◽  
pp. 77
Author(s):  
Oihane Mitxelena-Iribarren ◽  
Sara Lizarbe-Sancha ◽  
Jay Campisi ◽  
Sergio Arana ◽  
Maite Mujika
Keyword(s):  
Target Therapy ◽  
Treatment Options ◽  
Lipid Nanoparticles ◽  
Cell Number ◽  
Current Treatment ◽  
Drug Dose ◽  
Free Drug ◽  
Tumor Treatment ◽  
Equal Dose

The use of lipid nanoparticles as biodegradable shells for controlled drug delivery shows promise as a more effective and targeted tumor treatment than traditional treatment methods. Although the combination of target therapy with nanotechnology created new hope for cancer treatment, methodological issues during in vitro validation of nanovehicles slowed their application. In the current work, the effect of methotrexate (MTX) encapsulated in different matrices was evaluated in a dynamic microfluidic platform. Effects on the viability of osteosarcoma cells in the presence of recirculation of cell media, free MTX and two types of blank and drug-containing nanoparticles were successfully assessed in different tumor-mimicking microenvironments. Encapsulated MTX was more effective than the equal dose free drug treatment, as cell death significantly increased under the recirculation of both types of drug-loaded nanoparticles in all concentrations. In fact, MTX-nanoparticles reduced cell population 50 times more than the free drug when 150-µM drug dose was recirculated. Moreover, when compared to the equivalent free drug dose recirculation, cell number was reduced 60 and 100 points more under recirculation of each nanoparticle with a 15-µM drug concentration. Thus, the results obtained with the microfluidic model present MTX-lipid nanoparticles as a promising and more effective therapy for pediatric osteosarcoma treatment than current treatment options.

Impact of Removing the Race Coefficient in Renal Function Estimate Equations on Drug Dosage Recommendations

2021 ◽  
pp. 106002802110102
Author(s):  
Janine Miller ◽  
John P. Knorr
Keyword(s):  
Filtration Rate ◽  
Drug Dosage ◽  
Drug Dose ◽  
Epidemiology Study ◽  
Black African ◽  
Drug Dosing ◽  
Disease Epidemiology ◽  
Black Patients ◽  
The Impact ◽  
Level Of Agreement

Background The appropriateness of including the race coefficient in glomerular filtration rate (GFR) equations in Black patients is debated, and the impact on drug dosing is unknown. Objective This study explored the impact of removing the race coefficient on drug dosing in Black patients in comparison to conventional methods. Methods This was a retrospective study of hospitalized patients who self-identified as Black/African American and were prescribed an antimicrobial that includes renal dosage recommendations in the product labeling. The primary end point was the discordance between drug dosing recommendations derived by body surface area deindexed GFR estimated by the CKD-EPI equation (Chronic Kidney Disease Epidemiology study) with and without race versus recommendations derived from Cockcroft-Gault (CG). Results A total of 210 Black patients were included. There was an 18% rate of discordance when GFR was estimated with the race coefficient (GFR w/Race) versus without the race coefficient (GFR w/out Race). GFR w/out Race had a higher level of agreement with dosing by creatinine clearance (CrCl; κ = 0.779) than GFR w/Race versus CrCl (κ = 0.651). GFR w/out Race had less within-patient difference than GFR w/Race in comparison to CrCl (mean difference: −6.3 vs −18.0 mL/min). Conclusions and Relevance This represents the first report to examine the removal of the race coefficient and its implication on drug dose discordance. GFR w/out Race had a higher level of agreement and less drug dose discordance than GFR w/Race, in comparison to CrCl estimates. If GFR equations are considered comparable to CrCl for the purposes of guiding drug dosing, GFR w/out Race should be considered.

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