Journal of clinical pharmacy and therapeutics
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Review
Repurposing old drugs in oncology: Opportunities with clinical and regulatory challenges ahead.
In order to expedite the availability of drugs to treat cancers in a cost-effective manner, repurposing of old drugs for oncological indications is gathering momentum. Revolutionary advances in pharmacology and genomics have demonstrated many old drugs to have activity at novel antioncogenic pharmacological targets. We decided to investigate whether prospective studies support the promises of nonclinical and retrospective clinical studies on repurposing three old drugs, namely metformin, valproate and astemizole. ⋯ Well-designed prospective studies demonstrating efficacy are required for repurposing old drugs for oncology indications, just as they are for new chemical entities for any indication. Early and ongoing interactions with regulatory authorities are invaluable. We outline a tentative framework for a structured approach to repurposing old drugs for novel indications in oncology.
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Surveillance of drugs that most frequently induce acute kidney injury: A pharmacovigilance approach.
Acute kidney injury (AKI) often occurs in hospitalized patients, and it is an increasing problem worldwide. Recently, clinical studies have shown that there is a strong association between drug-induced AKI and poor outcomes, including the progression of chronic kidney disease and end-stage renal disease; however, limited data are available on drug-induced AKI. The purpose of this study was to clarify the rank-order of the association of all drugs with AKI using a spontaneous reporting system database. ⋯ A comprehensive study using a pharmacovigilance database enabled us to identify the drugs that most frequently induce AKI, raising physicians' awareness of the drugs in use for patients with potentially decreased renal function.
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Adverse drug reactions (ADRs) are an important cause of mortality during medical care. To our knowledge, no Ethiopian studies have reported on mortality due to ADRs in patients presenting to hospital from the community setting. The aim of this study was to determine the mortality rate attributable to ADRs in patients presenting to hospital, identify drugs implicated in the ADR-related deaths and identify factors contributing to ADR-related mortality at Jimma University Specialised Hospital (JUSH), south-west Ethiopia METHODS: This cross-sectional study included 1001 patients aged ≥18 years consecutively admitted to medical wards from May 2015 to August 2016. ADR-related mortality was determined through detailed review of medical records, laboratory tests and patient interviews followed by causality assessment by the Naranjo algorithm and expert consensus. ⋯ Fatal ADRs were common in patients presenting to hospital. The drugs implicated were mostly antitubercular and antiretroviral therapies, reflecting the high burden of HIV and tuberculosis in the study population. ADR-related deaths were significantly associated with poor nutritional status. The majority of ADR-related deaths were preventable, highlighting the need to develop a multidisciplinary approach to closely monitor patients who are prescribed antitubercular and antiretroviral therapies, particularly in patients with hepatic disease, a history of ADRs, who are malnourished and who are exposed to multiple medications.
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Formulae estimating glomerular filtration rate (GFR) are frequently used to guide drug dosing. The objectives of this prospective single-center study were to evaluate agreement between these equations and measured creatinine clearance (CrCl) in non-critically ill surgery patients with normal kidney function and augmented renal clearance (ARC, CrCl ≥ 130 mL/min/1.73 m²), to determine predictors for disagreement, define a GFR estimator cut-off value identifying ARC and determine the ARC prevalence and duration in non-critically ill surgical patients. ⋯ In surgical patients, eGFR frequently underestimates measured CrCl, especially in young patients with low ASA score. eGFR cut-offs predicting ARC were identified.
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Randomized Controlled Trial Clinical Trial
Evaluation of the effect of lanthanum carbonate hydrate on the pharmacokinetics of roxadustat in non-elderly healthy adult male subjects.
Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor currently being investigated for the treatment of anemia in chronic kidney disease. Lanthanum carbonate is a phosphate binder that is commonly used to treat hyperphosphatemia in patients with chronic kidney disease. This study investigated the effect of lanthanum carbonate on the pharmacokinetics, safety and tolerability of a single oral dose of roxadustat in healthy non-elderly adult male subjects. ⋯ Concomitant administration of a single oral dose of 100 mg roxadustat and 750 mg lanthanum carbonate three times daily did not impact the AUCinf or Cmax of roxadustat and was considered safe and well tolerated in non-elderly healthy adult male Japanese subjects.