Article
Clinical Neurology
Xin Liu, Gehang Ju, Xinyi Huang, Wenyu Yang, Lulu Chen, Chao Li, Qingfeng He, Nuo Xu, Xiao Zhu, Dongsheng Ouyang
Summary: This study aimed to develop a popPK model characterizing the disposition of SCIT in the Chinese population and proposed remedial strategies for non-adherence scenarios. Significant covariates impacting SCIT exposure were identified, and recommendations for dosage adjustments in different scenarios were provided based on CYP2C19 phenotypes. The study highlighted the importance of personalized medication based on patient characteristics and the utilization of popPK repository for precision dosing.
JOURNAL OF AFFECTIVE DISORDERS
(2024)
Article
Pharmacology & Pharmacy
Shujing Liu, Tao Xiao, Shanqing Huang, Xiaolin Li, Wan Kong, Ye Yang, Zi Zhang, Xiaojia Ni, Haoyang Lu, Ming Zhang, Dewei Shang, Yuguan Wen
Summary: This study aimed to establish a population pharmacokinetic model of escitalopram in Chinese psychiatric patients, identify factors influencing drug exposure, and compare the results with the therapeutic reference range through simulation. The study revealed the impact of age and CYP2C19 genotype on drug clearance. The findings suggest the need for cautious dosing regimens, especially for older patients who are poor metabolizers.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Clinical Neurology
Yun Kim, Anhye Kim, Jae-Yong Chung
Summary: A population PK/PD model was developed to characterize the delayed QT prolongation effect of escitalopram, with findings suggesting a relatively constant drug effect on QTc change over 24 hours post-dosing. The study provides useful information for monitoring electrocardiograms in patients receiving intensive care after drug administration.
JOURNAL OF AFFECTIVE DISORDERS
(2021)
Article
Chemistry, Medicinal
Pureum Kang, Chang-Keun Cho, Choon-Gon Jang, Seok-Yong Lee, Yun Jeong Lee, Chang-Ik Choi, Jung-Woo Bae
Summary: The study investigated the effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of gliclazide. The results showed that CYP2C9 and CYP2C19 genetic polymorphisms significantly affected the pharmacokinetics of gliclazide. However, the effects on plasma glucose and insulin responses were not significant, suggesting further research is needed.
ARCHIVES OF PHARMACAL RESEARCH
(2023)
Article
Medical Laboratory Technology
Pari Faraj, Astrid Hermansen, Espen Molden, Kristine Hole
Summary: The study found that a metabolic ratio of <0.24 strongly predicts the CYP2C19 poor metabolizer phenotype, offering a valuable alternative for personalized dosing of escitalopram.
THERAPEUTIC DRUG MONITORING
(2022)
Article
Microbiology
Sinenhlanhla Mtshali, Byron A. Jacobs
Summary: Physiologically based pharmacokinetic models have gained popularity in drug development and regulatory science. This study validates the model's effectiveness in predicting drug-drug interaction and the pharmacokinetics of antiretroviral and anti-TB drugs through mathematical solving and sensitivity analysis.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Ke Wang, Aimin Yang, Mai Shi, Claudia C. H. Tam, Eric S. H. Lau, Baoqi Fan, Cadmon K. P. Lim, Heung Man Lee, Alice P. S. Kong, Andrea O. Y. Luk, Brian Tomlinson, Ronald C. W. Ma, Juliana C. N. Chan, Elaine Chow
Summary: A pharmacogenetic study in East Asian population found associations between CYP2C19 polymorphisms and treatment response to sulfonylureas. Poor metabolizers of CYP2C19 had lower risk of treatment failure and were more likely to achieve the treatment target. Consideration of CYP2C19 polymorphisms could be beneficial for personalized sulfonylurea therapy.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Claudia Sommerer, Merce Brunet, Klemens Budde, Olga Millan, Lluis Guirado Perich, Petra Glander, Stefan Meuer, Martin Zeier, Thomas Giese
Summary: NFAT-regulated gene expression serves as a potential noninvasive predictive biomarker in Tac-treated renal allograft recipients, helping to detect patients at risk of acute rejection and infectious complications. High residual gene expression is associated with an increased risk of acute rejection, while low residual gene expression is linked to a higher incidence of viral complications, such as cytomegalovirus and BK virus replication. Monitoring NFAT-RGE provides additional useful information for physicians to achieve personalized Tac treatment.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Infectious Diseases
Pierre Chauvelot, Celine Dupieux-Chabert, Lelia Abad, Aubin Souche, Tristan Ferry, Jerome Josse, Frederic Laurent, Florent Valour
Summary: The study demonstrated that dalbavancin has the ability to effectively eradicate intraosteoblastic reservoir of Staphylococcus aureus in bone and joint infections. It showed significant reduction in bacterial inoculum at both low concentration and standard therapeutic doses, with similar efficacy to vancomycin but less efficient than rifampicin. Dalbavancin was found to be the only molecule significantly active at a low concentration.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Endocrinology & Metabolism
Ki Young Huh, Jun Gi Hwang, Wonjung Shin, Seungjae Baek, JaeDuk Choi, Nora Lee, Young Min Cho, Howard Lee
Summary: HM15136, a novel long-acting glucagon analogue, was shown to be safe and well tolerated in doses ranging from 10-120 μg/kg in a randomized, double-blind, placebo-controlled study. It increased blood glucose levels and suppressed the secretion of endogenous glucagon.
DIABETES OBESITY & METABOLISM
(2022)
Review
Chemistry, Medicinal
Xin Liu, Gehang Ju, Wenyu Yang, Lulu Chen, Nuo Xu, Qingfeng He, Xiao Zhu, Dongsheng Ouyang
Summary: Escitalopram (SCIT) is a widely used antidepressant and antianxiety medication with significant interindividual variability in pharmacokinetics. This study aimed to establish a parametric population pharmacokinetic (PPK) model of SCIT for personalized dosing. The impact of covariates on clearance, including CYP2C19 phenotype, weight, and age, was evaluated. It was found that dosing regimens should be tailored based on these factors. Furthermore, the exposure to SCIT among Chinese psychiatric patients was significantly higher compared to other populations, indicating a need for further investigation.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2023)
Review
Pharmacology & Pharmacy
Li Zhou, Micaela B. Reddy, Rajendar K. Mittapalli, Jing Yang, Donghua Yin
Summary: Combination therapies are commonly evaluated in the clinical development of oncology investigational agents, and the design needs to consider factors such as drug interactions and benefit/risk to study participants. This report proposes application scenarios for different trial designs and emphasizes the importance of generating robust exposure-response data for optimal dose selection.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Xinyi Huang, Chao Li, Chaopeng Li, Zhenyu Li, Xiaohui Li, Jianwei Liao, Tai Rao, Lulu Chen, Lichen Gao, Dongsheng Ouyang
Summary: The study demonstrates the differences in CYP2C19 gene frequency between Chinese and Caucasian populations, and highlights the necessity for individualized treatment with escitalopram in Chinese patients.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Ana Alarcia-Lacalle, Helena Barrasa, Javier Maynar, Andres Canut-Blasco, Carmen Gomez-Gonzalez, Maria Angeles Solinis, Arantxazu Isla, Alicia Rodriguez-Gascon
Summary: This study developed a rapid, simple and reproducible HPLC-UV method for quantifying ceftaroline in plasma samples, which was accurate and stable, successfully applied in two critically ill patients.
Review
Infectious Diseases
Cornelia B. Landersdorfer, Amanda Gwee, Roger L. Nation
Summary: Traditionally, ongoing i.v. antibiotic therapy has been believed to be superior to early i.v. to oral switch for severe infections. However, this belief may not be based on robust data and contemporary clinical studies. This review examines the rationale for an early switch and discusses barriers and perceptions related to this practice.
CLINICAL MICROBIOLOGY AND INFECTION
(2023)
Article
Pharmacology & Pharmacy
Trine Frederiksen, Johan Areberg, Arash Raoufinia, Ellen Schmidt, Tore Bjerregaard Stage, Kim Brosen
Summary: Accurate prediction of CYP2D6 phenotype from genotype information is important in pharmacotherapy. This study investigates the enzyme activity associated with different CYP2D6 alleles using population pharmacokinetic modeling. The results show that CYP2D6*2 allele has significantly lower enzyme activity, along with other alleles associated with reduced function.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Editorial Material
Pharmacology & Pharmacy
Julie Rudbech Krumborg, Nicolaj Mikkelsen, Per Damkier, Zandra Nymand Ennis, Daniel Pilsgaard Henriksen, Mads Lillevang-Johansen, Sidsel Arnspang Pedersen, Troels K. Bergmann
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Letter
Pharmacology & Pharmacy
Per Damkier, Michael Asger Andersen
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Review
Pharmacology & Pharmacy
Nicolaj Mikkelsen, Per Damkier, Sidsel Arnspang Pedersen
Summary: This review provides a clinical overview of serotonin syndrome, covering its pathophysiology, epidemiology, clinical manifestations, diagnostic criteria, differential diagnosis and treatment, as well as classifying serotonergic drugs and their mechanism of action. The emphasis is on the pharmacological context, as it is crucial for the detection and management of serotonin syndrome.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Pharmacology & Pharmacy
Ditte B. Iversen, Ann-Cathrine Dalgard Dunvald, Daniel M. Jespersen, Flemming Nielsen, Kim Brosen, Per Damkier, Helen S. Hammer, Oliver Poetz, Erkka Jaervinen, Tore B. Stage
Summary: This study investigated the inducible effect and autoinduction of flucloxacillin on CYP enzymes. Through a clinical pharmacokinetic study, it was found that flucloxacillin can induce the activity of CYP3A4. The results suggest that flucloxacillin may have clinically relevant drug-drug interactions with some narrow therapeutic range drugs that are substrates of CYP3A4.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Medicine, Research & Experimental
Trine Frederiksen, Johan Areberg, Ellen Schmidt, Tore Bjerregaard Stage, Kim Brosen
Summary: The polymorphism of the CYP2D6 gene leads to interindividual variability in CYP2D6 enzyme activity, while ethnicity could contribute to this variability. This study investigated interethnic differences in CYP2D6 activity using clinical datasets of three CYP2D6 substrates. The findings showed that African Americans had lower CYP2D6 activity compared to Asians and Whites among CYP2D6 normal metabolizers, and Asian carriers of CYP2D6 decreased function alleles tended to have higher CYP2D6 activity compared to Whites and African Americans among CYP2D6 intermediate metabolizers. The observed interethnic differences were driven by differences in CYP2D6 allele frequencies across ethnicities.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Clinical Neurology
Sandra S. S. Gylfadottir, Mustapha Itani, Alexander G. G. Kristensen, Jens R. R. Nyengaard, Soren Hein Sindrup, Troels S. S. Jensen, Nanna B. B. Finnerup, Pall Karlsson
Summary: This study assessed and compared the use of corneal confocal microscopy (CCM), intraepidermal nerve fiber density (IENFD), cold detection threshold (CDT), and warm detection threshold (WDT) in the diagnosis of diabetic polyneuropathy (DPN) in patients with type 2 diabetes. It was found that CCM had the lowest sensitivity compared with other small fiber measures.
Letter
Public, Environmental & Occupational Health
Per Damkier
PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
(2023)
Article
Public, Environmental & Occupational Health
C. L. Petersen, M. R. Hansen, T. Ohlenschlaeger, P. Damkier
Summary: This study investigated the quality of evidence and expected clinical value of treatments recommended by the Danish Medicines Council (DMC). The results showed that most recommendations by the DMC were based on low or very low-quality evidence according to GRADE ratings, and no recommendations were based on high-quality evidence. The added clinical value of the treatments was often not documented and rarely large.
Article
Pharmacology & Pharmacy
R. L. Bromley, M. Bickle Graz, M. Bluett-Duncan, C. Chambers, P. Damkier, K. Dietrich, H. Dolk, K. Grant, S. Mattson, K. J. Meador, H. Nordeng, T. F. Oberlander, A. Ornoy, A. Revet, J. Richardson, J. Rovet, L. Schuler-Faccini, E. Smearman, V. Simms, C. Vorhees, K. Wide, A. Wood, L. Yates, E. Ystrom, T. A. Supraja, J. Adams
Summary: The study aims to achieve consensus on the core neurodevelopmental outcomes, optimize methodologies, and overcome barriers in conducting pregnancy pharmacovigilance studies with neurodevelopmental outcomes. The vision is to establish a comprehensive understanding of neurodevelopmental outcomes in pregnancy pharmacovigilance through a complementary set of studies.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Oncology
N. H. Paulsen, P. Pfeiffer, M. Ewertz, S. Feddersen, H. S. Holm, T. K. Bergmann, C. Qvortrup, P. Damkier
Summary: The study aimed to compare the frequency of grade >3 FP-TOX before and after the implementation of DPYD genotyping. The results showed that the overall frequency of grade >3 FP-TOX was 27% in the DPYD genotype-guided group compared to 24% in the historical cohort. DPYD genotyping reduced the frequency of FP-related hospitalization from 19% to 0% in DPYD variant carriers. In wild-type patients, those with uracil >16 ng/mL had a higher frequency of FP-TOX than those with uracil <16 ng/mL.
Article
Obstetrics & Gynecology
Nete Lundager Klokker Rausgaard, Anne Broe, Mette Bliddal, Ellen Aagaard Nohr, Inge Olga Ibsen, Trine Lynge Albertsen, Pernille Ravn, Per Damkier
Summary: The prescription patterns of opioids during pregnancy in Denmark from 1997 to 2016 were investigated in this study. The overall use of opioids remained stable, with a decline in codeine use and a threefold increase in tramadol use. The number of pregnant women who continued to use opioids throughout pregnancy decreased, while the dosage among persistent users increased. The findings suggest a need for specific focus on opioid use in local Danish outpatient clinics and multidisciplinary pain centers during preconception and pregnancy.
EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY
(2023)
Article
Anesthesiology
Malin Erika Carmland, Melissa Dall Kreutzfeldt, Jakob Vormstrup Holbech, Peter Kolind Brask-Thomsen, Thomas Kroigard, Peter Norregaard Hansen, Hatice Tankisi, Troels Staehelin Jensen, Flemming Winther Bach, Soren Hein Sindrup, Nanna Brix Finnerup
Summary: This study investigated the efficacy of lacosamide in treating neuropathic pain, but the results were inconclusive. Although lacosamide has shown efficacy in animal models, its effect on human neuropathic pain remains uncertain.
EUROPEAN JOURNAL OF PAIN
(2023)
Article
Public, Environmental & Occupational Health
Philippe Grandjean, Alessandra Meddis, Flemming Nielsen, Iben H. Beck, Niels Bilenberg, Carly Goodman, Howard Hu, Christine Till, Esben Budtz-Jorgensen
Summary: By merging data from three birth cohort studies, the study found a statistically significant association between urine-fluoride concentrations and IQ, suggesting the need for protection against fluoride toxicity in pregnant women and children.
EUROPEAN JOURNAL OF PUBLIC HEALTH
(2023)
Article
Andrology
Ken Lund, Olav Sivertsen Garvik, Signe Marie Aagaard, Line Riis Jolving, Michael Due Larsen, Per Damkier, Bente Mertz Norgard
Summary: The study investigated the association between paternal use of non-steroid anti-inflammatory drugs and opioids before conception and adverse birth outcomes. Weak associations were found for paternal exposure to these medications and preterm birth/small for gestational age, but not for low Apgar score or major congenital malformations. The effect sizes were small and less likely to be clinically relevant.
