British Journal of Clinical Pharmacology

Background and ObjectiveHypertension is a common comorbidity of patients with COVID-19, SARS or HIV infection. Those patients are often treated with commonly used antiviral and antihypertensive agents concomitantly, such as ritonavir-containing regimens and nifedipine. Since ritonavir is a strong inhibitor of CYP3A, when nifedipine is combined with ritonavir-containing antiviral drugs, there is a potential risk of drug-drug interaction. This study aimed to provide guidance on nifedipine treatmen...

AimsTo describe the 1-year direct and indirect transition probabilities to premature discontinuation of statin therapy after concurrently initiating statins and CYP3A4-inhibitor drugs. MethodsA retrospective new-user cohort study design was used to identify (N=160828) patients who concurrently initiated CYP3A4-inhibitors (diltiazem, ketoconazole, clarithromycin, others) and CYP3A4-metabolized statins (statin DDI exposed, n = 104774) vs. other statins (unexposed, n = 56054) from the MarketScan C...

ObjectiveTo establish an optimized sotalol dosing strategy for fetal tachycardia by using a pregnancy computational model for dose simulations. MethodsA physiologically-based computational model, including pregnancy-related changes and placental transfer values, was established and verified. Simulations of the current dosing advises and prospective dosing scenarios were performed. To avoid maternal dose-related toxicity (QT-prolongation) we aimed for maternal concentrations <2.5 mg/L. Based on ...

ObjectiveIn spite of evidence and recommendations reflecting the importance of pharmacogenomic testing, most prescriptions are still given without testing. We demonstrate the real world implications of the use of testing and evaluate adverse events and outcomes in individuals who did not receive pharmacogenomic testing for clopidogrel. MethodsWe analyzed ~100K individuals with paired EHR and exome sequencing data from population health studies administered at multiple medical centers using the ...

The risk-benefit ratio associated with the use of repurposed drugs to treat 2019 SARS-CoV-2 related infectious disease (COVID-19) is complicated since benefits are awaited, not proven. A thorough literature search was conducted to source information on the pharmacological properties of 5 drugs and 1 combination (azithromycin, chloroquine, favipiravir, hydroxychloroquine, remdesivir, and lopinavir/ritonavir) repurposed to treat COVID-19. A risk assessment of drug-induced Long QT Syndrome (LQTS) a...

ObjectiveTo assess adverse events and safety of aripiprazole and olanzapine treatment. MethodsTwenty-four healthy volunteers receiving 5 daily oral doses of 10 mg aripiprazole and 5 mg olanzapine in a crossover clinical trial were genotyped for 46 polymorphisms in 14 genes by qPCR. Drug plasma concentrations were measured by HPLC-MS/MS. Blood pressure and 12-lead ECG were measured in supine position. Adverse events were also recorded. ResultsAripiprazole decreased diastolic blood pressure on t...

AimSeveral studies have reported population pharmacokinetic models for phenobarbital (PB), but the predictive performance of these models has not been well documented. This study aims to do external validation of the predictive performance in published pharmacokinetic models. MethodsTherapeutic drug monitoring data collected in neonates and young infants treated with PB for seizure control, was used for external validation. A literature review was conducted through PubMed to identify population...

Reports of metformin drug products contaminated with unacceptable levels of the probable human carcinogen N-Nitrosodimethylamine (NDMA) prompted a national sampling of post-market metformin drug products in early 2020. To broadly sample the United States market and minimize supply chain bias, metformin medication samples were crowdsourced directly from individuals across many states. 155 samples were received, and liquid chromatography-high resolution mass spectrometry tests for a panel of nitro...

Proton-pump inhibitors, PPIs, are widely prescribed and are available over the counter for prolonged reduction of stomach acid production and related disorders. PPIs irreversibly inhibit the hydrogen/potassium ATPase in gastric parietal cells. Recent retrospective studies have described an association between PPI use and depression. However, there is conflicting evidence that PPI therapy improves depressive symptoms. Considering the widespread use and over the counter availability of these drugs...

Hypoglycemia is a common issue in diabetes pharmacotherapy, with seasonal variations potentially influencing its occurrence. It has been reported that blood glucose levels exhibit seasonal variation, suggesting that seasonal factors may influence the occurrence of hypoglycemia. In this study, we examined the seasonal patterns of drug-related hypoglycemia according to causative drug categories using the Japanese Adverse Drug Event Report database. We assessed a total of 545,012 adverse event repo...

BackgroundLevetiracetam has been widely used as a treatment option for different types of epilepsy in both adults and children. Because of its large between-subject variability, several population pharmacokinetic studies have been performed to identify its pharmacokinetic covariates, and thus facilitate individualised therapy. ObjectiveThe aim of this review was to provide a synopsis for population pharmacokinetic studies of levetiracetam and explore the identified influencing covariates. Meth...

RelevanceManagement of symptoms like anxiety, delirium and agitation cannot be neglected in COVID-19 patients. Antipsychotics are usually used for the pharmacological management of delirium, and confusion and behavioral disturbances. The selection of concomitant COVID-19 medications and antipsychotics should be evidence-based and closely monitored ObjectiveTo systematically review evidence-based available on drug-drug interactions between COVID-19 treatments and antipsychotics. Evidence Review...

BackgroundAnticholinergic medications are widely used, however their use in older people has been linked to cognitive decline, dementia and increased mortality. This systematic review examines the literature investigating relationships between anticholinergic burden and risk of dementia, cognitive impairment, and outcomes in dementia. MethodsCochrane database and PubMed searches using the terms "anticholinergic" and "dementia" or "cognition" were performed up to May 2023. Outcomes included: (i)...

AimTo estimate the association between patterns of anticholinergic, benzodiazepine, and Z-drug medication use and change in cognitive function in middle-aged and older adults. MethodThis prospective cohort study used data from the first three waves of The Irish Longitudinal Study on Ageing (TILDA), including community-dwelling adults aged [&ge;]50 years followed for up to four years (n=7,027). Cognitive function was assessed using the Mini Mental State Examination, animal naming test, and word...

IntroductionPrescriptions involving multiple drugs issued by healthcare professionals are frequently at the origin of drug-drug interactions. These interactions represent a major cause of poor adherence, therapeutic failure, or potentially serious adverse events that may compromise the patients vital prognosis. In Cameroon, drug interactions have been studied on several occasions in hospital settings but only rarely in community pharmacies. This motivated our study, which aimed to analyse the ri...

AimsNitazoxanide is a broad-spectrum antiviral with potential application in a number of viral infections. Its use is limited by gastrointestinal side effects associated with increasing dose. In this study, we investigated the possibility of enhancing the exposure of its active metabolite, tizoxanide, through pharmacokinetic interaction with atazanavir/ritonavir. MethodThis was a crossover drug-drug interaction study, 18 healthy participants received a single dose of 1000 mg of nitazoxanide alo...

The safety, tolerability, pharmacokinetics, age-related effects of single (SD) and repeat (RD) doses of CMS121, a novel small molecule fisetin derivative, were evaluated in healthy adult volunteers. The effects of food were also evaluated in healthy young adult subjects. SD of up to 1800 mg or RD up to 900 mg/day for 7 days was generally well tolerated, with the majority of TEAEs mild in severity. Generally, the pharmacokinetics of CMS121 and its metabolites were well characterized and increased...

BackgroundPrescription opioids account for more than 40% of opioid induced mortalities. With the trend towards increased opioid prescribing set to continue rising, opioid-based adverse drug reactions, (ADRs) and their associated human and financial cost present a major global public health concern. The review examined the relationship between CYP2D6 phenotypes and opioid metabolising. The aim was to establish whether screening for CYP2D6 phenotypes would improve existing opioid dosing strategies...

IntroductionHealth information exchanges (HIEs) provide the capability to electronically move health care information among different health care information systems and store these data for downstream use cases. However, use of data from HIEs for postmarketing surveillance of medical products is not previously explored. ObjectivesTo conduct a pilot descriptive study characterizing data from MyHealth Access Network - a statewide HIE for Oklahoma, to understand its utility for conducting pharmac...

This study employed physiologically based pharmacokinetic (PBPK) modelling to compare the extent of fetal exposure between oral and long-acting injectable (LAI) aripiprazole and olanzapine. Adult and pregnancy PBPK models were developed and validated with relevant clinical data. Relevant indices of fetal exposure during pregnancy were predicted from concentration-time data at steady-state dosing for both oral and LAI formulations. Fetal Cmax for aripiprazole was 59-78% higher with LAI than oral,...