The impact of disease‐drug interactions on drug development and clinical practice

Cai, Hualin; Chen, Xia

doi:10.1111/bcp.14469

Cited by 5 publications

(1 citation statement)

References 9 publications

(12 reference statements)

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“…Depending on the lower or higher plasma exposure, it subsequently affects the drug’s therapeutic efficacy or toxicological behavior, respectively . Alike drug–drug interaction, disease–drug interaction is also a key concern nowadays to ensure the desired therapeutic efficacy. , In this context, information on the pharmacokinetic alteration in disease state for any medication, especially for a newly approved drug in the arena of antimicrobials, is highly needed to elucidate its pharmacokinetic/pharmacodynamic correlation and is consequently beneficial to combat the growing concern on AMR.…”

Section: Introductionmentioning

confidence: 99%

Impact of Disease States on the Oral Pharmacokinetics of EIDD-1931 (an Active Form of Molnupiravir) in Rats for Implication in the Dose Adjustment

Bhardwaj,

Gour,

Ahmed

et al. 2023

Mol. Pharmaceutics

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The pharmacokinetic alteration of an antimicrobial medication leading to sub-therapeutic plasma level can aid in the emergence of resistance, a global threat nowadays. In this context, molnupiravir (prodrug of EIDD-1931) is the most efficacious orally against corona virus disease (COVID-19). In addition to drug−drug interaction, the pharmacokinetics of a drug can significantly vary during any disease state, leading to disease−drug interaction. However, no information is available for such a recently approved drug. Therefore, we aimed to explore the oral pharmacokinetics of EIDD-1931 in seven chemically induced disease states individually compared to the normal state using various rat models. Induction of any disease situation was confirmed by the disease specific study(s) prior to pharmacokinetic investigations. Compared to the normal state, substantially lowered plasma exposure (0.47-and 0.63-fold) with notably enhanced clearance (2.00-and 1.56-fold) of EIDD-1931 was observed in rats of ethanol-induced gastric injury and carbon tetrachloride-induced liver injury states. Conversely, paclitaxel-induced neuropathic pain and cisplatin-induced kidney injury states exhibited opposite outcomes on oral exposure (1.43-and 1.50-fold) and clearance (0.69-and 0.65-fold) of EIDD-1931. Although the highest plasma concentration (2.26-fold) markedly augmented in the doxorubicin-induced cardiac injury state, streptozocin-induced diabetes and lipopolysaccharide-induced lung injury state did not substantially influence the pharmacokinetics of EIDD-1931. Exploring the possible phenomenon behind the reduced or boosted plasma exposure of EIDD-1931, results suggest the need for dose adjustment in respective diseased conditions in order to achieve desired efficacy during oral therapy of EIDD-1931.

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Section: Introductionmentioning

confidence: 99%

Impact of Disease States on the Oral Pharmacokinetics of EIDD-1931 (an Active Form of Molnupiravir) in Rats for Implication in the Dose Adjustment

Bhardwaj,

Gour,

Ahmed

et al. 2023

Mol. Pharmaceutics

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Association of Psychotropic Prescriptions With Non‐Registered Indications and the Risk of Mortality in Older Adults: A Danish Nationwide Cohort Study

Ishtiak‐Ahmed,

Jensen‐Dahm,

Christensen

et al. 2024

Int J Geriat Psychiatry

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Background and ObjectivePsychotropic drug use is common in older adults, with off‐label use reported despite limited understanding of the safety outcomes compared to on‐label use. Incomplete recordings of treatment indications in the Danish National Prescription Register (DNPR) raise concerns about potential off‐label medication use, particularly among older adults. We, therefore, investigated the association between psychotropic prescriptions with non‐registered indications in DNPR and the 1‐year all‐cause mortality in older adults, including subgroups with any psychiatric disorders, depression, or dementia.MethodsRegister‐based cohort study following all older adults (≥ 65) who redeemed a first‐time (since 1995) prescription of either antidepressants, antipsychotics, or benzodiazepine during 2006–2017. Redemption of a prescription with non‐registered indications in the DNPR was the exposure. The outcome, 1‐year all‐cause mortality was analyzed using Poisson regression, estimating incidence rate ratios with 95% confidence intervals, adjusting for socio‐demographics and clinical factors.Results32% of prescriptions filled by 202,067 individuals for antidepressants, 37% of 97,387 for antipsychotics, and 22% of 130,471 for benzodiazepines had non‐registered indications. No significant differences in mortality rates were found for antidepressants and antipsychotics with non‐registered indications, while higher mortality rates were associated with benzodiazepines, mitigated when excluding individuals receiving intravenous administrations representing end‐of‐life treatment. The results remained consistent in subgroup analyses in patients with any psychiatric disorders, depression, or dementia and further stratified analyses by sex and age.ConclusionsWe found that while psychotropic prescriptions with non‐registered indications in DNPR were prevalent in older adults, they were not associated with excess mortality.

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Overview of drugs and drug targets

Chakraborty,

Vijayasree,

Das

et al. 2024

Biochemical and Molecular Pharmacology in Drug Discovery

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The impact of disease‐drug interactions on drug development and clinical practice

Abstract: How to cite this article: Cai H, Chen X. The impact of diseasedrug interactions on drug development and clinical practice. Br

Cited by 5 publications

References 9 publications

Impact of Disease States on the Oral Pharmacokinetics of EIDD-1931 (an Active Form of Molnupiravir) in Rats for Implication in the Dose Adjustment

Impact of Disease States on the Oral Pharmacokinetics of EIDD-1931 (an Active Form of Molnupiravir) in Rats for Implication in the Dose Adjustment

Association of Psychotropic Prescriptions With Non‐Registered Indications and the Risk of Mortality in Older Adults: A Danish Nationwide Cohort Study

Overview of drugs and drug targets

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