AI Article Synopsis
Article Abstract
Purpose: Drug-drug interaction (DDI) potentials of lusutrombopag, a thrombopoietin receptor agonist, on the activity of cytochrome P450 (CYP) 3A and of cyclosporine, which inhibits P-glycoprotein and breast cancer resistance protein, on lusutrombopag pharmacokinetics were assessed via clinical studies and physiologically based pharmacokinetic (PBPK) modeling.
Methods: The effect of lusutrombopag on midazolam (a CYP3A probe substrate) pharmacokinetics was assessed in 15 healthy subjects receiving a single midazolam 5-mg dose with or without coadministration of lusutrombopag 0.75 mg for 6 days (first dose: 1.5-mg dose). The effect of cyclosporine on lusutrombopag pharmacokinetics was assessed in 16 healthy subjects receiving a single lusutrombopag 3-mg dose with or without a single cyclosporine 400- to 600-mg dose. PBPK modeling was employed to extrapolate the effect of lusutrombopag at the clinical dose (3 mg once daily) on midazolam pharmacokinetics.
Results: In the clinical study, mean ratios (90% confidence intervals [CIs]) of with/without lusutrombopag for maximum plasma concentration (C) and area under the plasma concentration-time curve (AUC) of midazolam were 1.01 (0.908-1.13) and 1.04 (0.967-1.11), respectively, indicating no effect of lusutrombopag on midazolam pharmacokinetics. PBPK modeling suggested no effect of lusutrombopag at the clinical dose on midazolam pharmacokinetics. Mean ratios (90% CIs) of with/without cyclosporine for lusutrombopag C and AUC were 1.18 (1.11-1.24) and 1.19 (1.13-1.25), respectively, indicating a slight increase in lusutrombopag exposure.
Conclusions: In consideration with in vitro data, the in vivo and in silico results suggested no clinically significant DDI potential of lusutrombopag with other medical products via metabolic enzymes and transporters.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661413 | PMC |
| http://dx.doi.org/10.1007/s00228-020-02960-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
[Clinical research progress of lusutrombopag for the treatment of thrombocytopenia in chronic liver disease].
Zhonghua Gan Zang Bing Za Zhi
October 2024
Senior Department of Infectious Diseases, the Fifth Medical Center of PLA General Hospital, Beijing100039, China Department of Immunology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi830054, China.
Thrombocytopenia is one of the common complications with the hematologic system in patients with chronic liver disease, which often causes poor quality of life and high risk of bleeding, thereby affecting their diagnosis, treatment, and prognosis. Platelet transfusion can improve the patient's declining platelet count to a certain extent, but it has problems such as high price and being easy to cause immune rejection. Thrombopoietin (TPO), as an important cytokine that affects platelet production, can bind to TPO receptors and activate megakaryocytes to produce platelets.
View Article and Find Full Text PDFAsymmetric Transfer Hydrogenation of Ketones Improved by PNN-Manganese Complexes.
J Org Chem
September 2024
College of Science, Hebei Agricultural University, Baoding 071001, China.
Chiral manganese(I) complexes that contain carbocyclic-fused 8-amino-5,6,7,8-tetrahydroquinolinyl groups that are appended with distinct -R substituents have proven to be effective catalysts in the asymmetric transfer hydrogenation (ATH) of a wide range of ketones (48 examples). Notably, proved to be the most productive catalyst, allowing an outstanding turnover number of 8300 with catalyst loadings as low as 0.01 mol %.
View Article and Find Full Text PDFFinal Results from the First European Real-World Experience on Lusutrombopag Treatment in Cirrhotic Patients with Severe Thrombocytopenia: Insights from the REAl-World Lusutrombopag Treatment in ITalY Study.
J Clin Med
July 2024
Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Roma, Italy.
Management of severe thrombocytopenia poses significant challenges in patients with chronic liver disease. Here, we aimed to evaluate the first real-world European post-marketing cohort of cirrhotic patients treated with lusutrombopag, a thrombopoietin receptor agonist, verifying the efficacy and safety of the drug. In the REAl-world Lusutrombopag treatment in ITalY (REALITY) study, we collected data from consecutive cirrhotic patients treated with lusutrombopag in 19 Italian hepatology centers, mostly joined to the "Club Epatologi Ospedalieri" (CLEO).
View Article and Find Full Text PDFUpdate on the Use of Thrombopoietin-Receptor Agonists in Pediatrics.
Hamostaseologie
August 2024
Department of Neonatology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
This review summarizes the rationale and current data on the use of thrombopoietin receptor agonists (TPO-RAs) for treating severe thrombocytopenia in infants, children, and adolescents. It focuses on substances that have been approved by the U.S.
View Article and Find Full Text PDFLusutrombopag Reduces the Risk of Hemoperitoneum Caused by Percutaneous Radiofrequency Ablation for Hepatocellular Carcinoma Compared with Platelet Transfusion.
Dig Dis
October 2024
Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
Introduction: Patients with liver cirrhosis develop thrombocytopenia and an increased risk of bleeding events after invasive procedures. Lusutrombopag, a thrombopoietin receptor agonist, can increase the platelet count. This study assessed whether lusutrombopag reduces the risk of hemoperitoneum following percutaneous radiofrequency ablation for hepatocellular carcinoma, compared with platelet transfusion.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!