journal
https://read.qxmd.com/read/38700454/st-john-s-wort-extract-with-a-high-hyperforin-content-does-not-induce-p-glycoprotein-activity-at-the-human-blood-brain-barrier
#21
JOURNAL ARTICLE
Myriam El Biali, Michael Wölfl-Duchek, Matthias Jackwerth, Severin Mairinger, Maria Weber, Karsten Bamminger, Stefan Poschner, Ivo Rausch, Natalie Schindler, Irene Hernández Lozano, Walter Jäger, Lukas Nics, Nicolas Tournier, Marcus Hacker, Markus Zeitlinger, Martin Bauer, Oliver Langer
St. John's wort (SJW) extract, a herbal medicine with antidepressant effects, is a potent inducer of intestinal and/or hepatic cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp), which can cause clinically relevant drug interactions. It is currently not known whether SJW can also induce P-gp activity at the human blood-brain barrier (BBB), which may potentially lead to decreased brain exposure and efficacy of certain central nervous system (CNS)-targeted P-gp substrate drugs. In this study, we used a combination of positron emission tomography (PET) imaging and cocktail phenotyping to gain a comprehensive picture on the effect of SJW on central and peripheral P-gp and CYP activities...
May 2024: Clinical and Translational Science
https://read.qxmd.com/read/38700326/acute-pharmacodynamic-responses-to-sitagliptin-drug-induced-increase-in-early-insulin-secretion-in-oral-glucose-tolerance-test
#22
JOURNAL ARTICLE
Amber L Beitelshees, Elizabeth A Streeten, Zhinous Shahidzadeh Yazdi, Hilary B Whitlatch, Braxton D Mitchell, Alan R Shuldiner, May E Montasser, Simeon I Taylor
DPP4 inhibitors are widely prescribed as treatments for type 2 diabetes. Because drug responses vary among individuals, we initiated investigations to identify genetic variants associated with the magnitude of drug responses. Sitagliptin (100 mg) was administered to 47 healthy volunteers. Several endpoints were measured to assess clinically relevant responses - including the effect of sitagliptin on glucose and insulin levels during an oral glucose tolerance test (OGTT). This pilot study confirmed that sitagliptin (100 mg) decreased the area under the curve for glucose during an OGTT (p = 0...
May 2024: Clinical and Translational Science
https://read.qxmd.com/read/38700290/pharmacokinetic-interactions-between-fexuprazan-a-potassium-competitive-acid-blocker-and-nonsteroidal-anti-inflammatory-drugs-in-healthy-males
#23
RANDOMIZED CONTROLLED TRIAL
Heejae Won, Eunwoo Kim, Jihye Chae, Hyejung Lee, Joo-Youn Cho, In-Jin Jang, Jae-Yong Chung, Min-Gul Kim, SeungHwan Lee
Fexuprazan, a novel potassium-competitive acid blocker, is expected to be used for the prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) induced ulcer. This study aimed to evaluate pharmacokinetic (PK) interactions between fexuprazan and NSAIDs in healthy subjects. A randomized, open-label, multicenter, six-sequence, one-way crossover study was conducted in healthy male subjects. Subjects randomly received one of the study drugs (fexuprazan 40 mg BID, celecoxib 200 mg BID, naproxen 500 mg BID, or meloxicam 15 mg QD) for 5 or 7 days in the first period followed by the combination of fexuprazan and one of NSAIDs for the same days and the perpetrator additionally administered for 1-2 days in the second period...
May 2024: Clinical and Translational Science
https://read.qxmd.com/read/38700272/concentration-qtc-modeling-of-sitravatinib-in-patients-with-advanced-solid-malignancies
#24
JOURNAL ARTICLE
Adam Dickinson, Yong Liu, Artem Uvarov, Thomas Peyret, J F Marier, Curtis Chin, Jonathan Q Tran
Sitravatinib (MGCD516) is an orally available, small molecule, tyrosine kinase inhibitor that has been evaluated in patients with advanced solid tumors. Concentration-corrected QT interval (QTc; C-QTc) modeling was undertaken, using 767 matched concentration-ECG observations from 187 patients across two clinical studies in patients with advanced solid malignancies, across a dose range of 10-200 mg, via a linear mixed-effects (LME) model. The effect on heart rate (HR)-corrected QT interval via Fridericia's correction method (QTcF) at the steady-state maximum concentration (Cmax,ss ) for the sitravatinib proposed therapeutic dosing regimen (100 mg malate once daily [q...
May 2024: Clinical and Translational Science
https://read.qxmd.com/read/38700261/a-systematic-review-and-meta-analysis-of-the-impacts-of-germline-pharmacogenomics-on-severe-toxicity-and-symptom-burden-in-adult-patients-with-cancer
#25
REVIEW
Senthil Lingaratnam, Mahek Shah, Joseph Nicolazzo, Michael Michael, John F Seymour, Paul James, Smaro Lazarakis, Sherene Loi, Carl M J Kirkpatrick
The clinical application of Pharmacogenomics (PGx) has improved patient safety. However, comprehensive PGx testing has not been widely adopted in clinical practice, and significant opportunities exist to further optimize PGx in cancer care. This systematic review and meta-analysis aim to evaluate the safety outcomes of reported PGx-guided strategies (Analysis 1) and identify well-studied emerging pharmacogenomic variants that predict severe toxicity and symptom burden (Analysis 2) in patients with cancer. We searched MEDLINE, EMBASE, CENTRAL, clinicaltrials...
May 2024: Clinical and Translational Science
https://read.qxmd.com/read/38700236/effects-of-the-selective-ampa-modulator-nbi-1065845-on-the-pharmacokinetics-of-midazolam-or-ethinyl-estradiol-levonorgestrel-in-healthy-adults
#26
RANDOMIZED CONTROLLED TRIAL
Swan Lin, Adrian Ionescu, Jessica Maynard-Scott, Mike Kennedy, David P Walling, Maura Furey, Jaskaran B Singh
This parallel-arm, phase I study investigated the potential cytochrome P450 (CYP)3A induction effect of NBI-1065845 (TAK-653), an investigational α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor potentiator in phase II development for major depressive disorder. The midazolam treatment arm received the sensitive CYP3A substrate midazolam on Day 1, followed by NBI-1065845 alone on Days 5-13; on Day 14, NBI-1065845 was administered with midazolam, then NBI-1065845 alone on Day 15. The oral contraceptive treatment arm received ethinyl estradiol-levonorgestrel on Day 1, then NBI-1065845 alone on Days 5-13; on Day 14, NBI-1065845 was administered with ethinyl estradiol-levonorgestrel, then NBI-1065845 alone on Days 15-17...
May 2024: Clinical and Translational Science
https://read.qxmd.com/read/38651744/a-pharmacokinetic-study-comparing-the-biosimilar-hec14028-and-dulaglutide-trulicity%C3%A2-in-healthy-chinese-subjects
#27
JOURNAL ARTICLE
Xianglei Gao, Yujing Di, Yuan Lv, Yingcai Luan, Yang Xiong, Yuli Xu, Yusheng Li, Linfeng Guo, Xiaoping Li, Li Deng, Yulei Zhuang, Jie Hou
This study aimed to evaluate the pharmacokinetics (PKs), safety, and immunogenicity of the biosimilar HEC14028 compared to reference Trulicity® (dulaglutide) in healthy male Chinese subjects. This study was a single-center, randomized, open, single-dose, parallel-controlled comparative Phase I clinical trial, including a screening period of up to 14 days, a 17-day observation period after administration, and a 7-day safety follow-up period. A total of 68 healthy male subjects were randomly assigned (1:1) to the test group (HEC14028) and the reference group (dulaglutide) (single 0...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38651283/postmarket-safety-communications-on-drugs-approved-in-japan-a-25-year-analysis
#28
JOURNAL ARTICLE
Yusuke Tanaka, Mototsugu Tanaka, Haruna Miyazawa, Ryohei Terashima, Makoto Miyazawa, Mutsuhiro Ikuma, Yoshihiko Tomita
Drug safety communications (DSCs) are essential tools for communicating important postmarket serious drug safety information to healthcare professionals and patients. Previous studies characterized DSCs issued by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA); however, knowledge about the activities of the Pharmaceuticals and Medical Devices Agency (PMDA)/the Ministry of Health, Labor and Welfare (MHLW) is limited. This study characterized DSCs by the PMDA/MHLW in comparison with previously reported DSCs by the FDA and the EMA...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38637962/response-to-dpyd-genotyping-panels-impact-of-population-diversity
#29
LETTER
Andrea Gaedigk, Amy J Turner, Cyrine E Haidar, Philip E Empey, Steven M Offer
No abstract text is available yet for this article.
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38634429/clinical-assessment-of-momelotinib-drug-drug-interactions-via-cyp3a-metabolism-and-transporters
#30
JOURNAL ARTICLE
Yu Liu Ho, Pete Gorycki, Geraldine Ferron-Brady, Paul Martin, Georgios Vlasakakis
Momelotinib-approved for treatment of myelofibrosis in adults with anemia-and its major active metabolite, M21, were assessed as drug-drug interaction (DDI) victims with a strong cytochrome P450 (CYP) 3A4 inhibitor (multiple-dose ritonavir), an organic anion transporting polypeptide (OATP) 1B1/1B3 inhibitor (single-dose rifampin), and a strong CYP3A4 inducer (multiple-dose rifampin). Momelotinib DDI perpetrator potential (multiple-dose) was evaluated with CYP3A4 and breast cancer resistance protein (BCRP) substrates (midazolam and rosuvastatin, respectively)...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38634417/dpyd-genotyping-panels-impact-of-population-diversity
#31
LETTER
Guilherme Suarez-Kurtz
No abstract text is available yet for this article.
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38629592/efficacy-safety-and-pharmacokinetics-of-isoniazid-affected-by-nat2-polymorphisms-in-patients-with-tuberculosis-a-systematic-review
#32
REVIEW
Thanakorn Surarak, Supatat Chumnumwat, Wichit Nosoongnoen, Pramote Tragulpiankit
N-acetyltransferase 2 (NAT2) genetic polymorphisms might alter isoniazid metabolism leading to toxicity. We reviewed the impact of NAT2 genotype status on the pharmacokinetics, efficacy, and safety of isoniazid, a treatment for tuberculosis (TB). A systematic search for research articles published in Scopus, PubMed, and Embase until August 31, 2023, was conducted without filters or limits on the following search terms and Boolean operators: "isoniazid" AND "NAT2." Studies were selected if NAT2 phenotypes with pharmacokinetics or efficacy or safety of isoniazid in patients with TB were reported...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38629502/influence-of-novel-cyp2c-haplotype-on-proton-pump-inhibitor-pharmacokinetics-in-children
#33
JOURNAL ARTICLE
Kathryn E Kyler, Andrea Gaedigk, Susan Abdel-Rahman, Vincent S Staggs, Robin E Pearce, Paul Toren, J Steven Leeder, Valentina Shakhnovich
In this brief report, we provide an analysis of the influence of a novel CYP2C haplotype (CYP2C:TG) on proton pump inhibitor (PPI) pharmacokinetics (PK) in children. The CYP2C:TG haplotype has been proposed to be associated with increased CYP2C19 activity. We sought to determine if this CYP2C:TG haplotype resulted in similar alterations in metabolism for proton pump inhibitors, which are primarily metabolized by CYP2C19. In a cohort of 41 children aged 6-21 participating in a PPI pharmacokinetic study, effects of the CYP2C:TG allele were assessed by fitting two linear regression models for each of the six PK outcomes assessed, the second of which accounted for the presence of the CYP2C:TG allele...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38629484/expert-survey-on-real-world-data-utilization-and-real-world-evidence-generation-for-regulatory-decision-making-in-drug-lifecycle-in-korea
#34
JOURNAL ARTICLE
Hankil Lee, Hyeon-Soo Ahn, Sol Kwon, Hye-Young Kang, Euna Han
As the importance of utilizing real-world data (RWD)/real-world evidence (RWE) for supporting regulatory scientific decision-making continues to grow, experiences and inputs from experts become crucial for developing a systematic and practice-oriented plan for the use of fit-for-purpose RWD/RWE. This study aimed to survey relevant experts from government agencies, industries, and academia to identify prerequisites for the drug life cycle in Korea. The questionnaire comprised the following: (A) the definition and categories of RWD/RWE, (B) the suitability and feasibility of using RWD/RWE at each authorization stage by the types of RWD, and (C) the challenges and solutions for the use of RWD/RWE...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38618871/sources-of-pharmacokinetic-and-pharmacodynamic-variability-and-clinical-pharmacology-studies-of-antiseizure-medications-in-the-pediatric-population
#35
REVIEW
Patricia D Maglalang, Jiali Wen, Christoph P Hornik, Daniel Gonzalez
Multiple treatment options exist for children with epilepsy, including surgery, dietary therapies, neurostimulation, and antiseizure medications (ASMs). ASMs are the first line of therapy, and more than 30 ASMs have U.S. Food and Drug Administration (FDA) approval for the treatment of various epilepsy and seizure types in children. Given the extensive FDA approval of ASMs in children, it is crucial to consider how the physiological and developmental changes throughout childhood may impact drug disposition. Various sources of pharmacokinetic (PK) variability from different extrinsic and intrinsic factors such as patients' size, age, drug-drug interactions, and drug formulation could result in suboptimal dosing of ASMs...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38618722/physiologically-based-modeling-reveals-different-risk-of-respiratory-depression-after-fentanyl-overdose-between-adults-and-children
#36
JOURNAL ARTICLE
Shilpa Chakravartula, Bradlee Thrasher, John Mann, Anik Chaturbedi, Xiaomei Han, Albert Dahan, Jeffry Florian, David Strauss, Zhihua Li
Despite a rapid increase in pediatric mortality rate from prescription and illicit opioids, there is limited research on the dose-dependent impact of opioids on respiratory depression in children, the leading cause of opioid-associated death. In this article, we extend a previously developed translational model to cover pediatric populations by incorporating age-dependent pharmacokinetic, pharmacodynamic, and physiological changes compared to adults. Our model reproduced previous perioperative clinical findings that adults and children have similar risk of respiratory depression at the same plasma fentanyl concentration when specific endpoints (minute ventilation, CO2 tension in the blood) were used...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38594824/randomized-placebo-controlled-double-blind-phase-i-trial-of-co-administered-pyronaridine-and-piperaquine-in-healthy-adults-of-sub-saharan-origin
#37
RANDOMIZED CONTROLLED TRIAL
Andrea Kuemmerle, Denis Gossen, Annick Janin, Andrew Stokes, Nada Abla, Maja Szramowska, Ulrike Lorch, Myriam El Gaaloul, Isabelle Borghini-Fuhrer, Stephan Chalon
Drug resistance to sulfadoxine-pyrimethamine and amodiaquine threatens the efficacy of malaria chemoprevention interventions in children and pregnant women. Combining pyronaridine (PYR) and piperaquine (PQP), both components of approved antimalarial therapies, has the potential to protect vulnerable populations from severe malaria. This randomized, double-blind, placebo-controlled (double-dummy), parallel-group, single site phase I study in healthy adult males or females of Black sub-Saharan African ancestry investigated the safety, tolerability, and pharmacokinetics of PYR + PQP (n = 15), PYR + placebo (n = 8), PQP + placebo (n = 8), and double placebo (n = 6) administered orally once daily for 3 days at the registered dose for the treatment of uncomplicated malaria...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38591811/pharmacokinetics-and-pharmacodynamics-of-mibavademab-a-leptin-receptor-agonist-results-from-a-first-in-human-phase-i-study
#38
RANDOMIZED CONTROLLED TRIAL
Andrew Gewitz, Jeanne Mendell, Yuhuan Wang, Charles Harris, Benjamin A Olenchock, Simona Podgrabinska, Wenjun Zheng, An Zhao, Hao Pan, Frédéric Vanhoutte, John D Davis
Mibavademab (previously known as REGN4461), a fully human monoclonal antibody, is being investigated for the treatment of conditions associated with leptin deficiency. Here, we report pharmacokinetics (PKs), pharmacodynamics, and immunogenicity from a phase I study in healthy participants (NCT03530514). In part A, lean or overweight healthy participants were randomized to single-ascending-dose cohorts of 0.3, 1.0, 3.0, 10, and 30 mg/kg intravenous (i.v.), or 300 and 600 mg subcutaneous doses of mibavademab or placebo...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38581109/the-association-of-cyp2c19-lof-alleles-with-adverse-clinical-outcomes-in-stroke-patients-taking-clopidogrel-an-updated-meta-analysis
#39
REVIEW
Mohitosh Biswas, Md Shahadat Hossain, Tahsin Ahmed Rupok, Md Sabbir Hossain, Chonlaphat Sukasem
The aggregated risk of recurrent stroke in stroke/transient ischemic attack (TIA) patients carrying CYP2C19 LoF alleles who take clopidogrel has not been investigated recently, and the available research is limited. This study aimed to perform an updated meta-analysis to assess the association between CYP2C19 LoF alleles and the risk of recurrent stroke in patients taking clopidogrel. Databases were searched for the literature on eligible studies. The end points were recurrent stroke, composite vascular events, and bleeding events...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38572980/advancing-the-utilization-of-real-world-data-and-real-world-evidence-in-clinical-pharmacology-and-translational-research-proceedings-from-the-ascpt-2023-preconference-workshop
#40
REVIEW
Jing Liu, Karen Rowland-Yeo, Almut Winterstein, Simon Dagenais, Qi Liu, Jeffrey S Barrett, Rui Zhu, Cyrus Ghobadi, Amita Datta-Mannan, Joy Hsu, Sujatha Menon, Mariam Ahmed, Pooja Manchandani, Paulien Ravenstijn
Real-world data (RWD) and real-world evidence (RWE) are now being routinely used in epidemiology, clinical practice, and post-approval regulatory decisions. Despite the increasing utility of the methodology and new regulatory guidelines in recent years, there remains a lack of awareness of how this approach can be applied in clinical pharmacology and translational research settings. Therefore, the American Society of Clinical Pharmacology & Therapeutics (ASCPT) held a workshop on March 21st, 2023 entitled "Advancing the Utilization of Real-World Data (RWD) and Real-World Evidence (RWE) in Clinical Pharmacology and Translational Research...
April 2024: Clinical and Translational Science
journal
journal
41994
2
3
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.