scholarly journals Meeting Regulatory Requirements for Drugs with a Narrow Therapeutic Index: Bioequivalence Studies of Generic Once-Daily Tacrolimus

2020 ◽  
Vol Volume 12 ◽  
pp. 151-160
Author(s):  
Kaja Gantar ◽  
Katja Škerget ◽  
Ilya Mochkin ◽  
Aleksander Bajc
Keyword(s):  
Therapeutic Index ◽  
Regulatory Requirements ◽  
Narrow Therapeutic Index ◽  
Once Daily

scholarly journals The art and science of drug titration

2020 ◽  
Vol 11 ◽  
pp. 204209862095891
Author(s):  
Aisling R. Caffrey ◽  
Eric P. Borrelli
Keyword(s):  
Real World ◽  
Therapeutic Index ◽  
Clinical Expertise ◽  
Coordination Of Care ◽  
Patient Centered ◽  
Narrow Therapeutic Index ◽  
Drug Dosing ◽  
Scientific Principles ◽  
Suboptimal Adherence ◽  
Personalized Approach

A “one-size-fits-all” approach has been the standard for drug dosing, in particular for agents with a wide therapeutic index. The scientific principles of drug titration, most commonly used for medications with a narrow therapeutic index, are to give the patient adequate and effective treatment, at the lowest dose possible, with the aim of minimizing unnecessary medication use and side effects. The art of drug titration involves the interplay of scientific drug titration principles with the clinical expertise of the healthcare provider, and an individualized, patient-centered partnership between the provider and the patient to review the delicate balance of perceived benefits and risks from both perspectives. Drug titration may occur as up-, down-, or cross-titration depending on whether the goal is to reach or maintain a therapeutic outcome, decrease the risk of adverse effects, or prevent withdrawal/discontinuation syndromes or recurrence of disease. Drug titration introduces additional complexities surrounding the conduct of clinical trials and real-world studies, confounding our understanding of the true effect of medications. In clinical practice, wide variations in titration schedules may exist due to a lack of evidence and consensus on titration approaches that achieve an optimal benefit-harm profile. Further, drug titration may be challenging for patients to follow, resulting in suboptimal adherence and may require increased healthcare-related visits and coordination of care amongst providers. Despite the challenges associated with drug titration, it is a personalized approach to drug dosing that blends science with art, and with supportive real-world outcomes-based evidence, can be effective for optimizing pharmacotherapeutic outcomes and improving drug safety.

scholarly journals Systematic treatment and prevention of cardiac digoxin toxicity

2021 ◽  
Author(s):  
Omar Rezk Alshaer ◽  
Abdullah Obaid Binobaid ◽  
Abdelelah Hesham Mofti ◽  
Mohannad Mahmood Sadagah ◽  
Khalid Mustafa Olwi ◽  
...  
Keyword(s):  
Therapeutic Index ◽  
Digoxin Toxicity ◽  
Clinical Settings ◽  
Clinical Effects ◽  
Systematic Treatment ◽  
Narrow Therapeutic Index ◽  
Serious Adverse Events ◽  
Treatment And Prevention ◽  
Cost Efficacy ◽  
The Cost

Digoxin has a narrow therapeutic index, such as complicated pharmacokinetics and dynamics.  Many drug interactions may occur when the administration of one drug alters the clinical effects of another. As a result, digoxin toxicity can be a common condition within clinical settings that might lead to the development of many morbidities and even mortality. Many studies were published to investigate the efficacy and safety of different management modalities to enhance the outcomes that follow digoxin administration. The aim of the study was to discuss the approaches to systematically treat and prevent the development of cardiac digoxin toxicity. The findings are based on evidence from previous studies in the literature. To be specific, Fab fragments are the most effective modalities that can be used to treat severe cases within ideal periods. However, evidence regarding their administration for asymptomatic or mild cases is still poor regarding the cost-efficacy and the development of serious adverse events. Physicians should primarily care for a better intervention as it is usually associated with a significantly more enhanced prognosis and clinical outcomes. Nevertheless, adequate monitoring of the patients and evaluation of their personal and medical history are important steps in the process, and further approaches are still needed. Also, detailed information about our intended outcomes is furtherly discussed within the manuscript.

Nano optical and electrochemical sensors and biosensors for detection of narrow therapeutic index drugs

2021 ◽  
Vol 188 (12) ◽  
Author(s):  
Omid Heydari Shayesteh ◽  
Reza Mahjub ◽  
Akram Ranjbar ◽  
Katayoun Derakhshandeh ◽  
Mahdi Jamshidi
Keyword(s):  
Electrochemical Sensors ◽  
Therapeutic Index ◽  
Narrow Therapeutic Index ◽  
Narrow Therapeutic Index Drugs

scholarly journals A comparative evaluation of lithium estimation for samples collected in different tubes and its stability on storage

2018 ◽  
Vol 10 (01) ◽  
pp. 056-059
Author(s):  
Saidaiah Ikkurthi ◽  
Srinivas Balachander ◽  
Bela Goyal ◽  
Altaf Ahmad Mir ◽  
Subho Chakrabarti ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Therapeutic Index ◽  
Blood Collection ◽  
Narrow Therapeutic Index ◽  
Glass Vial ◽  
Reference Collection ◽  
Collection Tube ◽  
Allowable Error ◽  
Bipolar Affective Disorders ◽  
Clot Activator

Abstract PURPOSE: Lithium (Li) is a well-established drug for the treatment of bipolar affective disorders. Li as a drug is known to possess a narrow therapeutic index. Thus, regular monitoring of blood Li in patients receiving Li therapy is essential. Plain tubes with clot activator are known to interfere with Li estimation. The current study was planned to compare Li estimation in sera from vacutainers with clot activator, and plasma from sodium heparinized vacutainers with that of Li estimation in sera from glass vials. The time-dependant stability of Li estimation on storage at 2°C–8°C for 48 h in these three set of tubes was also evaluated. MATERIALS AND METHODS: Blood from the patients on Li therapy (n = 100) was collected in 3 different collection tubes: plain vacutainer with clot activator (S), Sodium heparinized vacutainer (P) and Glass vial (G) and was analyzed by ion selective electrode (ISE) analyzer for Li levels. Secondary aliquots were also taken from each type of collection tube and stored at 2°C–8°C. Time-dependant stability of Li estimation was checked at 12 h, 24 h, and 48 h. ANOVA followed by Tukey's posttest was performed to calculate statistical significance taking glass vial as reference collection tube. Bland–Altman plots were plotted to compare between three collection tubes at baseline. Stability on storage was defined when >95% of the samples were within allowable error limit for that time point taking baseline levels as reference. RESULTS: A mean bias of 0.18 mmol/L and mean percentage bias of 19.9% in Li levels was observed between serum from (S) than serum from (G). This difference was found to be statistically significant. However, statistically nonsignificant mean bias of 0.02 mmol/L and mean percentage bias of 3.34% in Li levels was observed between plasma from (P) and serum from (G). Time-dependant stability was observed more in glass vials as compared to vacutainers with clot activator or sodium heparin. CONCLUSION: Serum from glass vial should be the preferred method for blood collection to determine Li levels.

Toxicity Related to Chloroquine Treatment of Resistant Vivax Malaria

2003 ◽  
Vol 37 (4) ◽  
pp. 526-529 ◽  
Author(s):  
Timothy ME Davis ◽  
David A Syed ◽  
Kenneth F Ilett ◽  
P Hugh R Barrett
Keyword(s):  
Vivax Malaria ◽  
Information Sources ◽  
Therapeutic Index ◽  
Narrow Therapeutic Index ◽  
Maximum Serum ◽  
Case Summary ◽  
Adequate Information ◽  
Chloroquine Treatment ◽  
Dosing Regimens ◽  
Maximum Serum Concentration

OBJECTIVE: To report a case of severe chloroquine toxicity in the presence of high-grade chloroquine-resistant Plasmodium vivax. CASE SUMMARY: A febrile 36-year-old seaman from Mumbai (Bombay) was prescribed >5 times the usual dose of chloroquine for malaria diagnosed empirically onboard ship. His fever resolved, but he developed symptoms consistent with those of chloroquine toxicity. Fever recurred 30 days after his initial presentation, and blood smear–positive vivax malaria was diagnosed. A serum chloroquine concentration at this time (91 μg/L) was above that considered effective for chloroquine-sensitive P. vivax (>15 μg/L). The patient responded to atovaquone plus proguanil followed by primaquine. DISCUSSION: The patient was given chloroquine by his captain in a dosage regimen appropriate for quinine (2 tablets 3 times daily for 7 d). Pharmacokinetic modeling suggested that the patient's initial over-treatment was as reported and that the predicted maximum serum concentration of chloroquine (902 μg/L) was within the range seen in fatal chloroquine overdose. CONCLUSIONS: Chloroquine-resistant vivax malaria is increasingly widespread, and transmission can occur within large tropical population centers. For drugs with a narrow therapeutic index such as chloroquine, recommended dosing regimens should be respected, and adequate information sources must be available where such drugs are dispensed by untrained personnel.

scholarly journals Polypharmacy May Be the Cause of Acute Lithium Intoxication at the Second Day of Treatment

Folia Medica ◽  
2016 ◽  
Vol 57 (3-4) ◽  
pp. 261-263 ◽  
Author(s):  
Irfan Tursun ◽  
Gokhan Tazegul ◽  
Ogur Karhan ◽  
Neslihan Gunes ◽  
Ece Ulukal ◽  
...  
Keyword(s):  
Mood Stabilizer ◽  
Therapeutic Index ◽  
Altered Mental Status ◽  
Muscle Rigidity ◽  
Lithium Intoxication ◽  
Lithium Level ◽  
Narrow Therapeutic Index ◽  
History Of ◽  
Acute Lithium ◽  
History Of Parkinson’S Disease

Abstract Lithium is frequently used as a mood stabilizer in patients with mood disorders. Lithium has a narrow therapeutic index and high toxicity. Predisposing factors for intoxication are advanced age, diet disturbances, comorbid medical conditions affecting heart, kidneys or central nervous system and polypharmacy. CASE REPORT: Here we present a case of a 74-year-old woman with a history of Parkinson’s disease, hypertension and bipolar disorder. She was using quetiapine, valsartan with hydrochlorothiazide and levodopa with carbidopa. She presented with altered mental status and muscle rigidity. The patient was admitted with acute lithium intoxication after her second dose of treatment. Blood lithium level increased to 3.58 mEq/L. The woman was hospitalized in the Internal Medicine Intensive Care Unit. With hydration, her symptoms resolved and her lithium level returned to normal after 118 hours. CONCLUSIONS: Prescribing physicians and emergency room physicians should be aware of conditions which may cause a decreased threshold for intoxication.

scholarly journals UN METODO SPETTROSCOPICO PER LA QUANTIFICAZIONE DI FARMACI IN FLUIDI BIOLOGICI

2020 ◽  
Author(s):  
Paolo Maria Ossi, et al. (#)
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Concentration ◽  
Biological Fluids ◽  
Therapeutic Index ◽  
Spectroscopic Technique ◽  
Metallic Surface ◽  
Narrow Therapeutic Index ◽  
Anti Epileptic Drug ◽  
Spectroscopic Signatures

An innovative spectroscopic technique to determine the drug concentration in biological fluids is discussed. We introduce the context of drugs with narrow therapeutic index in relation to epilepsy and Parkinson’s disease. We then recapitulate the essentials of Raman and enhanced Raman spectroscopy that makes use of a corrugated metallic surface. Optimizing the intensification of the spectroscopic signatures of a given analyte critically depends on the metal choice and on the fine details of the induced surface nanostructuring. We review the topic with emphasis on noble metal surfaces synthesized by pulsed laser ablation in inert gas at high pressure. The performance of optimized surfaces to determine the drug concentration in different fluids, including human blood, is discussed with reference to carbamazepine, an anti-epileptic drug widely adopted in Developing Countries and to apomorphine, a drug used to treat via subcutaneous injection patients with important manifestations of Parkinson’s disease.

Case of Severe Acute-on-Chronic Lithium Intoxication with 8.6 mmol/l and Prompt Hemodialysis

2020 ◽  
Vol 53 (05) ◽  
pp. 235-236
Author(s):  
Robert Haussmann ◽  
Markus Donix ◽  
Michael Bauer ◽  
Simone von Bonin ◽  
Ute Lewitzka
Keyword(s):  
Bipolar Disorder ◽  
Gold Standard ◽  
Therapeutic Index ◽  
Clinical Problem ◽  
Term Treatment ◽  
Optimal Treatment ◽  
Lithium Intoxication ◽  
Narrow Therapeutic Index ◽  
Long Term Treatment

Lithium has been the gold standard in the long-term treatment of bipolar disorder for more than 40 years 1. Due to a narrow therapeutic index lithium intoxication still is a common but potentially avoidable clinical problem 2. The possibility of SILENT-syndrome (syndrome of irreversible lithium-effectuated neurotoxicity) illustrates that prevention and optimal treatment of lithium intoxication is vitally important 3.

scholarly journals In Vivo Antimalarial Activities of Mono- and Bis Quaternary Ammonium Salts Interfering with Plasmodium Phospholipid Metabolism

2003 ◽  
Vol 47 (8) ◽  
pp. 2598-2605 ◽  
Author(s):  
Marie L. Ancelin ◽  
Michèle Calas ◽  
Anne Bonhoure ◽  
Serge Herbute ◽  
Henri J. Vial
Keyword(s):  
Quaternary Ammonium ◽  
Lethal Dose ◽  
Intraperitoneal Administration ◽  
Therapeutic Index ◽  
Phospholipid Metabolism ◽  
Quaternary Ammonium Salts ◽  
Ammonium Salts ◽  
Once Daily ◽  
Elimination Half

ABSTRACT We previously showed that quaternary ammonium salts have potent antimalarial activities against the blood stage of drug-resistant Plasmodium falciparum. In the present study, 13 compounds of this series were comparatively assessed in murine in vivo malarial models. Mice infected with Plasmodium berghei were successfully treated with 11 quaternary ammonium salts in a 4-day suppressive test with a once-daily intraperitoneal administration. The dose required to decrease parasitemia by 50% (ED50) ranged from 0.04 to 4.5 mg/kg of body weight. For six mono- and three bis-quaternary ammonium salts, the therapeutic indices (i.e., 50% lethal dose and ED50) were higher than 5, and at best, around 20 to 30 for five of them (E6, E8, F4, G5, and G25), which is comparable to that of chloroquine under the same conditions. Plasmodium chabaudi was significantly more susceptible to G5, G15, and G25 compounds than P. berghei. Similar therapeutic indices were obtained, regardless of the administration mode or initial parasitemia (up to 11.2%). Parasitemia clearance was complete without recrudescence. Subcutaneously administered radioactive compounds had a short elimination half-life in mice (3.5 h) with low bioavailability (17.3%), which was likely due to the permanent cationic charge of the molecule. The high in vivo therapeutic index in the P. chabaudi-infected mouse model and the absence of recrudescence highlight the enormous potential of these quaternary ammonium salts for clinical malarial treatment.

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