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Ursolic Acid: A Pentacyclic Triterpene from Plants in Nanomedicine
Published in Mahfoozur Rahman, Sarwar Beg, Mazin A. Zamzami, Hani Choudhry, Aftab Ahmad, Khalid S. Alharbi, Biomarkers as Targeted Herbal Drug Discovery, 2022
Monalisha Sen Gupta, Md. Adil Shaharyar, Mahfoozur Rahman, Kumar Anand, Imran Kazmi, Muhammad Afzal, Sanmoy Karmakar
Qian et al. recently examined the safety and activity of UA liposomes against tumors in 20 subjects of age 18-75, in whom the presence of advanced solid tumors had already confirmed by cytological or histological data. All subjects received intravenously administered UA liposomes at doses of 56, 74, and 98 mg/m2 for 14 consecutive days over a 21-day time period. All the subjects were evaluated at the tolerability and toxicity scale. The results demonstrating the safety profile of UA liposome treatment particularly for subjects with advanced solid tumors. Indeed, 60% of patients achieved stable disease status after two treatment cycles (Wang et al., 2013).
Clinical Trial Design and Concepts Specific for Biologic Agents in the Treatment of Rheumatic Diseases
Published in Thomas F. Kresina, Monoclonal Antibodies, Cytokines, and Arthritis, 2020
As most of these agents are immunomodulators, it is important, even in the Phase I study, to enroll patients with active disease. It is unlikely that information gained in normal human subjects will be generalizable to the patient population. Many biologic products have been introduced into malignant disease settings and subsequently studied in autoimmune diseases such as rheumatoid arthritis. Again, it is not readily apparent how much of the information from a study in malignant disease can be generalized into another clinical setting. Often the issues of tolerability are distinctly different among different patient populations, not to mention confounding difficulties with concomitant medications and other organ system involvement. One is reminded of the old clinical “saw” that patients with rheumatoid arthritis are extremely sensitive to the administration of many types of drugs. Our experience with CD5 Plus has shown distinctly different tolerability profiles in patients with graft vs. host disease compared with patients with rheumatoid arthritis. Additionally, in studies of several other autoimmune diseases such as diabetes and aplastic anemia, the tolerability profile varied among the different patient populations.
Clinical Pharmacology of the Anti-Tuberculosis Drugs
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Gerry Davies, Charles Peloquin
ETH and PTM are dosed at 15–20 mg/kg per day up to a maximum of 1 g. To improve tolerability, the drugs are usually dosed gradually over a period of days. Once daily administration is possible but twice daily dosing is often used because individual doses of greater than 500 mg may not be tolerated.
Drug tolerability versus drug safety
Published in Journal of Dermatological Treatment, 2023
Stuti Prajapati, Rachel Tao, Steven R. Feldman
The United States Food and Drug Administration (FDA) defines drug tolerability as the degree to which the drug’s adverse effects can be tolerated by the subject (1). Drug tolerability is determined by the patient’s subjective experience and how it affects their quality of life while taking the drug. For example, fatigue and nausea are subjective drug tolerability issues, as opposed to dangerous objective health risk issues (2). Apremilast, an oral phosphodiesterase 4 inhibitor approved to treat psoriasis and psoriatic arthritis in the United States, has tolerability issues such as nausea, and headaches but is still safe, given the lack of common serious adverse effects associated with it (3). A drug’s tolerability is an important outcome directly and indirectly because of its potential effects on patient adherence. If the drug is intolerable, the patient may stop taking it entirely.
UK medical cannabis registry: assessment of clinical outcomes in patients with headache disorders
Published in Expert Review of Neurotherapeutics, 2023
Martha Nicholas, Simon Erridge, Lara Bapir, Manaswini Pillai, Nishaanth Dalavaye, Carl Holvey, Ross Coomber, James J Rucker, Mark W Weatherall, Mikael H Sodergren
Current migraine management includes a combination of acute and preventative pharmacological therapies [12,13]. Acute therapies include non-steroidal anti-inflammatory drugs, paracetamol and, for more severe attacks, triptans [12]. Patients suffering from frequent migraine attacks may require additional preventative therapies, including repurposed medications such as beta-blockers, tricyclic antidepressants, and anticonvulsants [12]. However, these regimes are associated with unpredictable effectiveness, with only one in three patients reporting symptom improvement [14]. Moreover, side effects like fatigue, rashes, dizziness, weight gain, and constipation lend to their poor tolerability [15]. Furthermore, due to frequent requirement for analgesia, patients may subsequently suffer from medication overuse headache (MOH) in the attempt to alleviate their migraine, resulting in a vicious circle of headache symptoms [16,17]. In recent years, new therapies have been introduced for migraine, including onabotulinumtoxin A injections, and monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor [12]; whilst effective for many patients, these treatments are expensive, and access to them remains limited [12]. Therefore, a clear demand remains to develop novel therapeutics.
A safety evaluation of aripiprazole in the treatment of schizophrenia
Published in Expert Opinion on Drug Safety, 2020
Adrian Preda, Bryan B. Shapiro
In an ideal world, the adverse effects of a drug would be clearly qualified as related or not related and correlated with measures of adherence and drug levels in blood and target tissues. In this world, clinical trials, which generate the bulk of safety data and set the standard for tolerability assessments, indiscriminately qualify a variety of outcomes as adverse effects. Most of the adverse effects are further qualified as ‘drug related’ as to do otherwise, i.e. call an adverse effect ‘not related’ requires a level of cause-effect certainty that is rarely met in the murky universe of biological correlates. Except for Phase 1 trials and inpatient clinical trials, adherence is usually assessed based on patient’s report. For clinical populations where adherence is known to be problematic, such as patients with schizophrenia, poor or partial adherence also represents a significant limitation of clinical trials [53]. Even in the setting of ideal adherence, individual differences in pharmacokinetics can result in different drug levels, and thus in different risks for adverse effects. Yes, drug levels are not routinely reported in clinical trials. When performed, trials do not report or stratify risk based on drug levels. Last but not least, from a pharmacodynamics perspective, a given drug level can result in different efficacy and tolerability profiles, due to differences in individual pharmacodynamics. An important limitation of this safety review is that the available safety data on aripiprazole is from this world, not an ideal world, and thus subject to all the above limitations.