Ye Yuan, Liang Li, Justin Earp, Lian Ma, Venkatesh Atul Bhattaram, Vishnu Sharma, Alexander Tong, Yaning Wang, Jiang Liu, Hao Zhu
The application of model-informed drug development (MIDD) has revolutionized drug development and regulatory decision making, transforming the process into one that is more efficient, effective, and patient centered. A critical application of MIDD is to facilitate dose selection and optimization, which play a pivotal role in improving efficacy, safety, and tolerability profiles of a candidate drug. With the surge of interest in small interfering RNA (siRNA) drugs as a promising class of therapeutics, their applications in various disease areas have been extensively studied preclinically...
March 1, 2024: Journal of Clinical Pharmacology
Sung-Ling Tang, Kai-Yi Wang, Wen-Kai Hsiao, Chi-Kang Lin
Ensuring the safety of analgesics during lactation is crucial for women of childbearing potential. Available data regarding the transfer of nalbuphine for postoperative acute pain via breast milk are limited to the postmarketing experience. This lactation study aimed to assess nalbuphine and dinalbuphine sebacate concentrations in breast milk from lactating women with postoperative pain treated with dinalbuphine sebacate extended-release injection (150 mg dinalbuphine sebacate/2 mL Naldebain). Breast milk was collected throughout the 5-day posthospitalization interval from 20 mothers injected with one dose of extended-release dinalbuphine sebacate intramuscularly...
March 1, 2024: Journal of Clinical Pharmacology
Huijuan Wang, Junyan Wang, Bin Lin, Huifen Zhang, Yangyang Sun, Yuanyuan Wu, Weifeng Ye, Jing Miao
Perampanel (PER) is a new type of antiseizure medication used for partial or generalized seizures. However, the plasma concentration shows obvious individual variability in children. The present study aims to ascertain the effect of age, comedications, and cytochrome P450 (CYP) 3A4/5 polymorphisms on PER exposure in Chinese pediatric patients with epilepsy. Clinical data were retrospectively collected in a tertiary children's hospital medical records system from January 2021 to December 2022. The influence factors on the daily dose, plasma concentration, and concentration-to-dose ratio (CDR) of PER were investigated...
February 21, 2024: Journal of Clinical Pharmacology
Haiping Yao, Yanyan Wang, Yan Peng, Zhixiong Huang, Guoping Gan, Zhu Wang
Ceftazidime/avibactam (CAZ/AVI) is a combination of a well-known third-generation, broad-spectrum cephalosporin with a new beta-lactamase inhibitor that has been approved for the treatment of various infectious diseases (especially multidrug-resistant Gram-negative bacterial infections) by the Food and Drug Administration (FDA). The current study extensively assessed CAZ/AVI-related adverse events (AEs) in the real world through data mining of the FDA Adverse Event Reporting System (FAERS) database to better understand toxicities...
February 20, 2024: Journal of Clinical Pharmacology
Xian Ping, Guopeng Wang, Dongmei Gao
The aim of this study was to use a combination of physiologically based pharmacokinetic (PBPK) modeling and urinary glucose excretion (UGE) modeling to predict the time profiles of pharmacokinetics (PK) and UGE for the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMP). Additionally, the study aims to explore the compensatory effect of SGLT1 in renal glucose reabsorption (RGR) when SGLT2 is inhibited. The PBPK-UGE model was developed using physicochemical and biochemical properties, renal physiological parameters, binding kinetics, glucose, and Na+ reabsorption kinetics by SGLT1/2...
February 16, 2024: Journal of Clinical Pharmacology
John N van den Anker
No abstract text is available yet for this article.
February 14, 2024: Journal of Clinical Pharmacology
Nikita Gupta, Mitali Paryani, Snehal Patel, Aditi Bariya, Anshu Srivastava, Yashwant Pathak, Shital Butani
Idiopathic pulmonary fibrosis (IPF) is a continuous, progressive, and lethal age-related respiratory disease. It is characterized by condensed and rigid lung tissue, which leads to a decline in the normal functioning of the lungs. The pathophysiology of IPF has still not been completely elucidated, so current strategies are lagging behind with respect to improving the condition of patients with IPF and increasing their survival rate. The desire for a better understanding of the pathobiology of IPF and its early detection has led to the identification of various biomarkers associated with IPF...
February 12, 2024: Journal of Clinical Pharmacology
Islam R Younis, Fan Wang, Ahmed A Othman
This work aimed to assess the feasibility of using population pharmacokinetics (popPK) to generate virtual healthy control groups in organ impairment studies. Data from 11 organ impairment studies containing 18 organ impairment arms and 13 healthy control groups across 7 drugs were analyzed. Area under the concentration-time curve (AUC) and maximum concentration (Cmax ) were calculated from popPK-simulated individual concentration-time profiles for participants in the healthy control groups, accounting for the participant's specific covariate(s) (N = 1000 replicates)...
February 12, 2024: Journal of Clinical Pharmacology
Scott R Penzak, Marilyn Bulloch
β-Phenyl-γ-aminobutyric acid (phenibut) is an analog of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) that was first synthesized in Russia in the early 1960s. It is marketed as a nootropic (smart drug) to improve cognitive performance, and to treat generalized and social anxiety, insomnia, and alcohol withdrawal. The use of phenibut is legal in the USA and it is widely available online without a prescription. Increased public awareness of phenibut has led to a growing number of reports of acute intoxication and withdrawal...
February 10, 2024: Journal of Clinical Pharmacology
Nastya Kassir, David McDougall, Denison Kuruvilla, Sean Kim, Shaun Kumar, Ahmadur Rahman, Thorsten Ruf, Sravanthi Cheeti, Wendy Ankrom
Pralsetinib is a highly potent oral kinase inhibitor of oncogenic RET (rearranged during transfection) fusions and mutations. Pralsetinib received approval from the United States Food and Drug Administration for the treatment of patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC), and received accelerated approval for the treatment of patients with RET fusion-positive thyroid cancer. Exposure-response (ER) analyses of efficacy were performed separately in patients with thyroid cancer and in patients with NSCLC, but data for all patients were pooled for the safety analysis...
February 9, 2024: Journal of Clinical Pharmacology
Wenwen Du, Xiaoxing Wang, Dan Zhang, Xianbo Zuo
The determination of the appropriate initial dose for tacrolimus is crucial in achieving the target concentration promptly and avoiding adverse effects and poor prognosis. However, the trial-and-error approach is still common practice. This study aimed to establish a prediction model for an initial dosing algorithm of tacrolimus in patients receiving a lung transplant. A total of 210 lung transplant recipients were enrolled, and 26 single nucleotide polymorphisms (SNP) from 18 genes that could potentially affect tacrolimus pharmacokinetics were genotyped...
February 8, 2024: Journal of Clinical Pharmacology
Yuan Yuan, Shenghua He, Huanxia Liu, Yuanhong He, Ruifeng Zhou, Yuan Yao, Ke Yin, Chunrong Lyu
This study intended to investigate the impact of long-term tenofovir fumarate (TDF) antiviral regimen on renal function in human immunodeficiency virus (HIV)-infected patients with low-risk of kidney injury. The observational study involving 100 HIV-infected patients without underlying diseases who achieved virological suppression and immunological recovery after sustained antiviral regimen of TDF+ lamivudine+ efavirenz (TLE) for 3.19 years. Renal function, including estimated glomerular filtration rate (eGFR), blood and urine β2 microglobulin, and other parameters, was assessed every 3 months over a period of 2...
February 7, 2024: Journal of Clinical Pharmacology
Stephen J Balevic, Daniel Weiner, Christoph P Hornik, Michael Cohen-Wolkowiez, Daniel Gonzalez, Xiaoming Wang, Meixiang Xu, Sherif Z Abdel-Rahman, Erik Rytting
The use of indomethacin to delay delivery in preterm labor (PTL) is widely accepted; however, the optimal dosage of indomethacin in pregnancy is unknown. Here, we perform population pharmacokinetic (PK) and pharmacodynamic (PD) analyses, characterize the plasma disposition of indomethacin in pregnant women with PTL, and relate indomethacin exposure to delayed delivery and maternal/neonatal safety. We analyzed plasma and urine samples collected from a multicenter, prospective, opportunistic PK/PD study of indomethacin in pregnant women 12-32 weeks gestation admitted with PTL...
February 5, 2024: Journal of Clinical Pharmacology
Jinpeng Lu, Xinyi Lin, Haiwen Teng, Yansong Zheng
Hepatocellular carcinoma (HCC) is often diagnosed in advanced stages. Following sorafenib, lenvatinib (LENV) has been approved as a first-line treatment option for unresectable HCC. In the past few years, at least 9 large-scale cohort studies have examined the efficacy and safety of LENV compared to atezolizumab plus bevacizumab (ATE/BEV) in unresectable HCC, but there is currently no direct meta-analysis conducted for a comprehensive consolidation. To provide the most updated meta-analysis of the clinical efficacy and safety of ATE/BEV versus LENV for patients with unresectable HCC...
February 4, 2024: Journal of Clinical Pharmacology
Marya Antônya Werdan Romão, Leonardo Pinto, Ricardo Carvalho Cavalli, Geraldo Duarte, Natália Valadares de Moraes, Khaled Abduljalil, Fernanda de Lima Moreira
Nifedipine is used for treating mild to severe hypertension and preventing preterm labor in pregnant women. Nevertheless, concerns about nifedipine fetal exposure and safety are always raised. The aim of this study was to develop and validate a maternal-placental-fetal nifedipine physiologically based pharmacokinetic (PBPK) model and apply the model to predict maternal, placental, and fetal exposure to nifedipine at different pregnancy stages. A nifedipine PBPK model was verified with nonpregnant data and extended to the pregnant population after the inclusion of the fetoplacental multicompartment model that accounts for the placental tissue and different fetal organs within the Simcyp Simulator version 22...
February 2, 2024: Journal of Clinical Pharmacology
James Mease, Anuradha Ramamoorthy, Xinning Yang, Rajanikanth Madabushi, Elimika Pfuma Fletcher, Issam Zineh
Statins are widely prescribed and highly susceptible to pharmacokinetic (PK)-based drug-drug interactions (DDIs). To date, there has not been a comprehensive analysis of the basis upon which statin DDI recommendations in US Food and Drug Administration (FDA) prescribing information (PI) are derived. We have conducted such an analysis. We also assessed the degree of concordance of statin DDI recommendations in FDA PI and those provided in common tertiary clinical resources. We catalogued statin DDI information, including PK data and management recommendations, for statin precipitant drugs approved from 2010 to 2021, available from FDA PI and tertiary clinical resource databases...
February 1, 2024: Journal of Clinical Pharmacology
Lindsay Clegg, Ed Freshwater, Amanda Leach, Tonya Villafana, Ulrika Wählby Hamrén
Nirsevimab, a monoclonal antibody with an extended half-life, is approved for the prevention of respiratory syncytial virus (RSV) disease in all infants in Canada, the EU, Great Britain, and the USA. A population pharmacokinetics (PK) model was built to describe the PK of nirsevimab in preterm and term infants, and to evaluate the influence of covariates, including body weight and age, in infants. Nirsevimab PK was characterized by a 2-compartment model with first-order clearance (CL) and first-order absorption following intramuscular (IM) administration...
January 31, 2024: Journal of Clinical Pharmacology
Kayla R Tunehag, Blessy George, Sherbet Samuels, Karen Vo, Vikram Arya, Gelareh Abulwerdi, Gilbert J Burckart
Food effect (FE) studies characterize food-drug interactions that may alter the efficacy or safety of a drug, but these studies are not conducted in pediatric patients. Pediatric patients have substantial physiologic, anatomic, and dietary differences from adults, which may result in differences in their FE considerations. Therefore, the objective of this study was to identify oral drug products approved for use in pediatric patients aged <6 years with an FE observed in adults. Additional objectives were to summarize the therapeutic areas, pharmacokinetic effects, and labeling instructions that resulted from these studies...
January 31, 2024: Journal of Clinical Pharmacology
Leah Sera, Carrie Hempel-Sanderoff
Cannabis-based therapeutics have garnered increasing attention in recent years as patients seek alternative treatments for various medical conditions. This narrative review provides a comprehensive overview of the science behind the medical use of cannabis, focusing on the medical evidence for commonly treated conditions. In addition, the review addresses the practical considerations of using cannabis as a therapeutic agent, offering insights into dosing strategies, variations in cannabinoid formulation, and individual patient responses...
December 25, 2023: Journal of Clinical Pharmacology
Lyudmila Yermukhanova, Kerbez Kimatova, Rysty Nazarbayeva, Zhanar Dostanova, Gulshara Aimbetova
The human body is subservient to the age-related changes that affect not only the outer appearance, but also organs and tissues. They also concern the processes of pharmacokinetics and dynamics. This means that the absorption, distribution and metabolism of drugs used by an elderly patient will be slowed down. Therefore, it becomes necessary to prescribe a special dosing regimen for older people. An actual problem is also that with age, many patients require more drugs than young people. This increases the risk of side effects, because many drugs are difficult to combine with each other...
December 21, 2023: Journal of Clinical Pharmacology
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