F Groen, J R Prins, M N Lub-de Hooge, H L J Winter, J G W Kosterink, D J Touw, P Mian
INTRODUCTION: Understanding the pharmacokinetics (PK) of antimicrobial drugs in pregnant women is crucial to provide effective and safe treatment. This study is part of a series that systematically reviews literature on the PK and analyzes if, based on the changed PK, evidence-based dosing regimens have been developed for adequate target attainment in pregnant women. This part focusses on antimicrobials other than penicillins and cephalosporins. METHODS: A literature search was conducted in PubMed according to the PRISMA guidelines...
March 20, 2023: Clinical Pharmacokinetics
Marloes van Hout, Pablo Forte, Thomas B Jensen, Cristina Boschini, Tine A Bækdal
BACKGROUND: Prescribing information instructs taking oral semaglutide (a glucagon-like peptide-1 analogue) in the fasting state, followed by a post-dose fasting period of ≥ 30 min. This trial compared the recommended dosing schedule with alternative schedules. METHODS: This was a randomised, single-centre, multiple-dose, open-label, five-armed, parallel-group trial in healthy subjects who received once-daily oral semaglutide (3 mg for 5 days followed by 7 mg for 5 days)...
March 17, 2023: Clinical Pharmacokinetics
Chengcong Chen, Xiaoqing Fan, Lin Zhang, Peng Xu, Huixi Zou, Xing Zhao, Manish Gupta, Yan Summer Feng, Xu Steven Xu, Xiaoyu Yan
BACKGROUND AND OBJECTIVE: The designs of first-in-human (FIH) studies in oncology (e.g., 3 + 3 dose escalation design) usually do not provide a sufficient sample size to determine the dose-response relationship for efficacy. This study aimed to assess the feasibility of using monoclonal antibody (mAb) clearance as a biomarker for efficacy to facilitate the identification of potentially efficacious doses across cancer types and drug targets. METHODS: We performed electronic searches of the [email protected] website, the European Medicines Agency website, and PubMed to identify reports of FIH trials of approved mAbs in oncology...
March 17, 2023: Clinical Pharmacokinetics
Luis Ortega-Paz, Salvatore Giordano, Davide Capodanno, Roxana Mehran, C Michael Gibson, Dominick J Angiolillo
Cardiovascular diseases are the leading cause of death worldwide. Although there have been substantial advances over the last decades, recurrent adverse cardiovascular events after myocardial infarction are still frequent, particularly during the first year of the index event. For decades, high-density lipoprotein (HDL) has been among the therapeutic targets for long-term prevention after an ischemic event. However, early trials focusing on increasing HDL circulating levels showed no improvement in clinical outcomes...
March 16, 2023: Clinical Pharmacokinetics
Mikkel Askjær Agersnap, Kim Sonne, Kim Mark Knudsen, Wladyslaw Sulowicz
No abstract text is available yet for this article.
March 13, 2023: Clinical Pharmacokinetics
Islam Younis, Elijah Weber, Cara Nelson, Brian J Kirby, Gong Shen, Deqing Xiao, Timothy R Watkins, Ahmed A Othman
BACKGROUND AND OBJECTIVE: Cilofexor is a selective farnesoid X receptor (FXR) agonist in development for the treatment of nonalcoholic steatohepatitis and primary sclerosing cholangitis. Our objective was to evaluate potential drug-drug interactions of cilofexor as a victim and as a perpetrator. METHODS: In this Phase 1 study, healthy adult participants (n = 18-24 per each of the 6 cohorts) were administered cilofexor in combination with either perpetrators or substrates of cytochrome P-450 (CYP) enzymes and drug transporters...
March 11, 2023: Clinical Pharmacokinetics
Ana Victoria Ponce-Bobadilla, Sven Stodtmann, Mong-Jen Chen, Insa Winzenborg, Sven Mensing, Jonas Blaes, Tobias Haslberger, Loic Laplanche, Ingeborg Dreher, Nael M Mostafa
BACKGROUND AND OBJECTIVE: Predicting adalimumab pharmacokinetics (PK) for patients impacted by anti-drug antibodies (ADA) has been challenging. The present study assessed the performance of the adalimumab immunogenicity assays in predicting which patients with Crohn's disease (CD) and ulcerative colitis (UC) have low adalimumab trough concentrations; and aimed to improve predictive performance of adalimumab population PK (popPK) model in CD and UC patients whose PK was impacted by ADA...
March 11, 2023: Clinical Pharmacokinetics
Eunsol Yang, Sang Chun Ji, In-Jin Jang, SeungHwan Lee
BACKGROUND AND OBJECTIVE: CYP2C19-mediated drug interactions of acid-reducing agents are clinically important given the high possibility of concomitant administration with CYP2C19 substrates. This study aimed to evaluate the effect of tegoprazan on the pharmacokinetics (PK) of a CYP2C19 substrate, proguanil, compared with vonoprazan or esomeprazole. METHODS: A two-part, randomized, open-label, two-sequence, three-period crossover study was conducted in 16 healthy CYP2C19 extensive metabolizers (eight subjects per part)...
March 10, 2023: Clinical Pharmacokinetics
Neang S Ly, Jing Li, Raffaella Faggioni, Lorin K Roskos, Marcia S Brose
BACKGROUND AND OBJECTIVE: In the USA, cabozantinib was approved for the treatment of patients aged ≥ 12 years with radioiodine-refractory differentiated thyroid cancer (DTC) who progressed on prior vascular endothelial growth factor (VEGFR)-targeted therapy based on the Phase 3 COSMIC-311 trial, which evaluated cabozantinib 60 mg/day versus placebo. Approved dosing is 60 mg/day for adults and for pediatric patients aged ≥ 12 years with body surface area (BSA) ≥ 1...
March 4, 2023: Clinical Pharmacokinetics
Prakruti S Rao, Nisha Modi, Nam-Tien Tran Nguyen, Dinh Hoa Vu, Yingda L Xie, Monica Gandhi, Roy Gerona, John Metcalfe, Scott K Heysell, Jan-Willem C Alffenaar
BACKGROUND AND OBJECTIVE: Quantifying exposure to drugs for personalized dose adjustment is of critical importance in patients with tuberculosis who may be at risk of treatment failure or toxicity due to individual variability in pharmacokinetics. Traditionally, serum or plasma samples have been used for drug monitoring, which only poses collection and logistical challenges in high-tuberculosis burden/low-resourced areas. Less invasive and lower cost tests using alternative biomatrices other than serum or plasma may improve the feasibility of therapeutic drug monitoring...
March 4, 2023: Clinical Pharmacokinetics
Angela Elma Edwina, Nada Dia, Erwin Dreesen, Thomas Vanassche, Peter Verhamme, Isabel Spriet, Lorenz Van der Linden, Jos Tournoy
Older adults, the fastest growing population, represent almost 50% of all users of direct oral anticoagulants (DOACs). Unfortunately, we have very little relevant pharmacological and clinical data on DOACs, especially in older adults with geriatric profiles. This is highly relevant as pharmacokinetics and pharmacodynamics (PK/PD) often differ substantially in this population. Hence, we need to obtain a better understanding of the PK/PD of DOACs in older adults, to ensure appropriate treatment. This review summarises the current insights into PK/PD of DOACs in older adults...
March 2, 2023: Clinical Pharmacokinetics
Eko Setiawan, Menino Osbert Cotta, Mohd-Hafiz Abdul-Aziz, Doddy Widjanarko, Hernycane Sosilya, Dwi Lily Lukas, Steven C Wallis, Suzanne Parker, Jason A Roberts
BACKGROUND: The pharmacokinetic variability of ampicillin-sulbactam in adults has not been extensively described, particularly in patients with a reduced renal function (i.e., < 60 mL/min). OBJECTIVE: This study investigated the population pharmacokinetics of ampicillin and sulbactam in patients with a wide range of renal functions and sought to define dosing approaches that have a high likelihood for optimising drug exposure. METHODS: Serial blood samples were collected from 16 adult patients receiving intravenous ampicillin-sulbactam in general wards...
February 28, 2023: Clinical Pharmacokinetics
Yan Rong, Tony Kiang
Corticosteroids (steroids) are commonly used concurrently with mycophenolic acid (MPA) as the first-line immunosuppression therapy for the prevention of rejection in solid organ transplantations. Steroids are also commonly administered with MPA in various autoimmune disorders such as systemic lupus erythematosus and idiopathic nephrotic syndrome. Despite various review articles having suggested the presence of pharmacokinetic interactions between MPA and steroids, definitive data have not yet been demonstrated...
February 27, 2023: Clinical Pharmacokinetics
Mikkel Askjær Agersnap, Kim Sonne, Kim Mark Knudsen, Wladyslaw Sulowicz
BACKGROUND: Glepaglutide is a novel, ready-to-use, long-acting, glucagon-like peptide-2 (GLP-2) analog intended for the treatment of patients with short bowel syndrome (SBS). This study investigated the impact of renal function on the pharmacokinetics and safety of glepaglutide. METHODS: In this 3-site, non-randomized, open-label study, 16 subjects were enrolled: 4 with severe renal impairment (eGFR 15 to < 30 mL/min/1.73 m2 ), 4 with end stage renal disease (ESRD) not on dialysis (eGFR < 15 mL/min/1...
February 21, 2023: Clinical Pharmacokinetics
Krina Mehta, Tingjie Guo, Piet H van der Graaf, J G Coen van Hasselt
BACKGROUND: Site-of-action concentrations for bedaquiline and pretomanid from tuberculosis patients are unavailable. The objective of this work was to predict bedaquiline and pretomanid site-of-action exposures using a translational minimal physiologically based pharmacokinetic (mPBPK) approach to understand the probability of target attainment (PTA). METHODS: A general translational mPBPK framework for the prediction of lung and lung lesion exposure was developed and validated using pyrazinamide site-of-action data from mice and humans...
February 19, 2023: Clinical Pharmacokinetics
Ling Song, Xiaoxu Wang, Jingfang Sun, Xinyu Hu, Haiyan Li, Pei Hu, Dongyang Liu
AIM: To apply model-informed drug development (MIDD) approach to support the decision making in drug development and accelerate the clinical development of janagliflozin, an orally selective SGLT2 inhibitor. METHOD: We previously developed a mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model of janagliflozin based on preclinical data to optimize dose design in the first-in-human (FIH) study. In the current study, we used clinical PK/PD data of the FIH study to validate the model and then simulate the PK/PD profiles of multiple ascending dosing (MAD) study in healthy subjects...
February 18, 2023: Clinical Pharmacokinetics
Yan Ji, Vitaly Yartsev, Michelle Quinlan, Paolo Serra, Yingbo Wang, Abhijit Chakraborty, Michelle Miller
BACKGROUND AND OBJECTIVE: Renal impairment is common in patients with cancer and can alter the PK and thus the safety and efficacy of drugs. We assessed the impact of renal impairment during treatment with ribociclib, a cyclin-dependent kinase 4/6 inhibitor, and determined dose recommendations for patients with advanced breast cancer with renal impairment. METHODS: A comprehensive assessment integrating pharmacokinetic, safety, and efficacy data from a phase I dedicated renal impairment study in non-cancer subjects and six phase I-III trials in patients with cancer was performed...
February 17, 2023: Clinical Pharmacokinetics
Antoine Tarral, Lionel Hovsepian, Thierry Duvauchelle, Yves Donazzolo, Mathilde Latreille, Mathieu Felices, Virginie Gualano, Sophie Delhomme, Olaf Valverde Mordt, Severine Blesson, Pascal Voiriot, Nathalie Strub-Wourgaft
BACKGROUND AND OBJECTIVES: Acoziborole is a novel boron-containing candidate developed as an oral drug for the treatment of human African trypanosomiasis (HAT). Results from preclinical studies allowed progression to Phase 1 trials. We aimed to determine the best dose regimen for all stages of HAT. METHODS: Acoziborole was assessed in 128 healthy adult males of sub-Saharan African origin living in France. The study included a single oral administration of a 20- to 1200-mg dose in a randomised double-blind study in cohorts of 8 (6 active, 2 placebo) to assess safety, tolerability, and pharmacokinetics...
February 10, 2023: Clinical Pharmacokinetics
Pierre Bourgoin, Jules Lecomte, Mehdi Oualha, Lionel Berthomieu, Tony Pereira, Emeline Davril, Fabien Lamoureux, Nicolas Joram, Alexis Chenouard, Thomas Duflot
No abstract text is available yet for this article.
February 8, 2023: Clinical Pharmacokinetics
Jose David Gomez-Mantilla, Fenglei Huang, Sheila Annie Peters
BACKGROUND AND OBJECTIVE: Mechanistic static and dynamic physiologically based pharmacokinetic models are used in clinical drug development to assess the risk of drug-drug interactions (DDIs). Currently, the use of mechanistic static models is restricted to screening DDI risk for an investigational drug, while dynamic physiologically based pharmacokinetic models are used for quantitative predictions of DDIs to support regulatory filing. As physiologically based pharmacokinetic model development by sponsors as well as a review of models by regulators require considerable resources, we explored the possibility of using mechanistic static models to support regulatory filing, using representative cases of successful physiologically based pharmacokinetic submissions to the US Food and Drug Administration under different classes of applications...
February 8, 2023: Clinical Pharmacokinetics
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.