Article
Oncology
Rene J. Boosman, Thomas P. C. Dorlo, Nikki de Rouw, Jacobus A. Burgers, Anne-Marie C. Dingemans, Michel M. van den Heuvel, Lizza E. L. Hendriks, Bonne Biesma, Joachim G. J. Aerts, Sander Croes, Ron H. J. Mathijssen, Alwin D. R. Huitema, Rob Ter Heine
Summary: Pemetrexed is an important component in the first-line treatment of patients with non-squamous non-small cell lung cancer, but its use is limited in patients with renal impairment due to hematological toxicity. Research aimed to explore the relationship between pemetrexed exposure and toxicity in renal impairment patients, finding that the approved dose may result in a high probability of severe neutropenia in this population, suggesting the need for alternative dosing regimens for safe administration.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Anesthesiology
Thomas Stoehr, Pieter J. Colin, Joachim Ossig, Marija Pesic, Keith Borkett, Peter Winkle, Michel M. R. F. Struys, Frank Schippers
Summary: The study demonstrated that no dose adjustments are required in patients with hepatic or renal impairment when using remimazolam, and no unexpected adverse events related to remimazolam were observed in these patients.
BRITISH JOURNAL OF ANAESTHESIA
(2021)
Article
Pharmacology & Pharmacy
Nikki de Rouw, Rene J. Boosman, Alwin D. R. Huitema, Luuk B. Hilbrands, Elin M. Svensson, Hieronymus J. Derijks, Michel M. van den Heuvel, David M. Burger, Rob ter Heine
Summary: Population pharmacokinetic analysis of pemetrexed showed that renal function significantly influences drug clearance, with up to 84% of total clearance attributed to renal function. This finding highlights the importance of considering renal impairment in patients receiving pemetrexed therapy. Additionally, a three-compartment model may contribute to prolonged drug exposure during elimination phases.
CLINICAL PHARMACOKINETICS
(2021)
Article
Pharmacology & Pharmacy
Lingling Ye, Xiang You, Jie Zhou, Chaohui Wu, Meng Ke, Wanhong Wu, Pinfang Huang, Cuihong Lin
Summary: A PBPK model was used to assess the pharmacokinetics of daptomycin in children with renal impairment, showing increased exposure levels in children with varying degrees of renal impairment, indicating the need for further dose adjustments of daptomycin.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Mitsuo Higashimori, Kensuke Ishikawa, Michael Gillen, Diansong Zhou
Summary: A physiologically based pharmacokinetic (PBPK) model was developed to predict the systemic exposure of glycopyrronium in patients with severe renal impairment, showing a potential increase in AUC without the need for dose adjustment.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Teresa Garcia-Martinez, Maria Dolores Belles-Medall, Maria Garcia-Cremades, Raul Ferrando-Piqueres, Victor Mangas-Sanjuan, Matilde Merino-Sanjuan
Summary: This study aimed to develop a population pharmacokinetic/pharmacodynamic model of daptomycin and establish optimal dose recommendations in patients with normal and impaired renal function. The results indicate that bactericidal effects for Gram+ strains can be achieved with specific daily doses based on body weight and renal function. By evaluating the impact of different dosing regimens on treatment outcomes, the study provides insights for optimizing the use of daptomycin.
Review
Biochemistry & Molecular Biology
Sarah Hanigan, Jeong M. Park
Summary: Drug transporters, metabolic enzymes, and renal clearance play significant roles in the pharmacokinetics of DOACs. Current recommendations for the management of pharmacokinetic DOAC DDIs lack considerations for concomitant renal dysfunction. Empiric dose adjustments based on pharmacokinetic data alone should be avoided, and future research on identification of DOAC therapeutic ranges and target patient populations is needed.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2022)
Article
Infectious Diseases
Alexia Chauzy, Salim Bouchene, Vincent Aranzana-Climent, Jonathan Clarhaut, Christophe Adier, Nicolas Gregoire, William Couet, Claire Dahyot-Fizelier, Sandrine Marchand
Summary: Understanding antibiotic concentration-time profiles in the CNS is crucial for treating severe CNS infections. A PBPK model was developed to predict brain concentration-time profiles of antibiotics and simulate the impact of pathophysiological changes on CNS profiles. The model described well the pharmacokinetic profiles of metronidazole in plasma, ECF, and CSF.
Article
Pharmacology & Pharmacy
Yi Li, Jianda Lu, Yue Kang, Xiaoyong Xu, Xin Li, Yuancheng Chen, Kun Wang, Xiaofen Liu, Yaxin Fan, Hailan Wu, Yu Wang, Jiali Hu, Jicheng Yu, Jufang Wu, Beining Guo, Yingyuan Zhang, Xin Zeng, Ming Zhao, Jun Xue, Jing Zhang
Summary: The optimal dosing regimen for patients with severe renal impairment was found to be 0.5 g nemonoxacin every 48 hours, which showed higher probability of target attainment and cumulative fraction of response against Streptococcus pneumoniae and Staphylococcus aureus. Other dosage regimens were found to be insufficient in covering the pathogens even if minimum inhibitory concentration was at 1 mg/L.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Infectious Diseases
Saskia E. Zieck, Suzanne L. de Vroom, Frouke Ph. Mulder, Gitte van Twillert, Ron A. A. Mathot, Suzanne E. Geerlings, Reinier M. van Hest
Summary: This study aimed to investigate whether the PK/PD target of ceftazidime is attained in adult patients on general wards with adequate and impaired renal function receiving regular and guideline-recommended reduced doses of ceftazidime. The results showed that the PK/PD target of ceftazidime (50% T > MIC) was achieved in most patients with adequate or impaired renal function, when applying the clinical breakpoint MIC for Pseudomonas aeruginosa of 8 mg/L.
Article
Pharmacology & Pharmacy
Hengli Zhao, Yilin Wei, Kun He, Xiaoyu Zhao, Hongli Mu, Qing Wen
Summary: This study developed a physiologically based pharmacokinetic (PBPK) model to predict the pharmacokinetics of Janagliflozin in T2DM patients. The results showed that the exposure of Janagliflozin increased with the severity of cirrhosis, while it remained stable regardless of the severity of renal impairment. This suggests that dose adjustment may not be critical for these patients, but a risk benefit assessment is recommended.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Vivek Purohit, Yeamin Huh, Jessica Wojciechowski, Anna Plotka, Stephanie Salts, Jeremias Antinew, Angela Dimitrova, Timothy Nicholas
Summary: This article presents the pharmacokinetics and safety study of Ritlecitinib in participants with hepatic and renal impairment. Two innovative approaches, statistical analysis and in silico simulation, were used to analyze the data. The results show that patients with renal impairment do not require dose modification of Ritlecitinib. These analyses provide reference data and adequate pharmacokinetic models for drug development in special populations.
Review
Pharmacology & Pharmacy
Sharayu Govardhane, Pravin Shende
Summary: This article reviews the modulation of delivery systems using subarachnoid space for the treatment of central nervous system ailments and highlights the use of nanocarrier systems for subarachnoid delivery. It also discusses the potential applications of nanomedicine in treating brain conditions.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Ruijuan Xu, Hong Tang, Lin Chen, Weihong Ge, Jin Yang
Summary: The study successfully utilized a PBPK model to predict the pharmacokinetic profiles of apixaban under different conditions, and found that exposure to apixaban varies with interacting drugs or renal impairment. The results suggest that different populations may require different dosages when using apixaban.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Chengjie Ke, Xiang You, Cuihong Lin, Jiarui Chen, Guimu Guo, Wanhong Wu, Lingling Ye, Pinfang Huang
Summary: A physiologically based pharmacokinetic (PBPK) model was developed to predict pregabalin (PGB) dosage for pediatric patients with renal impairment (RI). The model was validated and used to simulate the disposition of PGB in the healthy population and adults with RI. The results showed that the model accurately predicted the exposure to PGB in different populations and suggested optimal dosage regimens for pediatric patients with varying degrees of RI.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)