1. Safflower injection (SI) is extracted from Chinese herbal medicine safflower that comprises many active components. Warfarin is a common anticoagulant and has exhibited drug interactions with several herbal products. This study aimed to investigate the effects of SI on pharmacodynamics and pharmacokinetics of warfarin in rats. 2. Wistar rats were randomly divided into blank control group, SI group, warfarin control group and SI + warfarin group, respectively. In SI and SI + warfarin groups, rats were injected with SI (1.6 mL/kg/d, i.p.) for 14 days. Warfarin (0.2 mg/kg) was given orally on the eighth day. Saline was given as control. The blood samples were collected at various time points. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. UPLC-MS/MS was used to determine the plasma concentrations of S(R)-warfarin, and the pharmacokinetic parameters were calculated. 3. PT, APTT in SI and SI + warfarin rats increased significantly compared with corresponding control rats. The pharmacokinetic parameters including C, t, AUC and AUC of S-warfarin and R-warfarin in SI + warfarin rats were higher than those in warfarin control rats. 4. These findings suggest that SI significantly increases the anticoagulant effect of warfarin by affecting its pharmacodynamic and pharmacokinetic parameters.
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http://dx.doi.org/10.1080/00498254.2017.1361051 | DOI Listing |
J Pharmacokinet Pharmacodyn
January 2025
Department of Clinical Pharmacy and Pharmacy Administration, West China school of Pharmacy, Sichuan University, Chengdu, 610064, China.
Alogliptin is a highly selective inhibitor of dipeptidyl peptidase-4 and primarily excreted as unchanged drug in the urine, and differences in clinical outcomes in renal impairment patients increase the risk of serious adverse reactions. In this study, we developed a comprehensive physiologically-based quantitative systematic pharmacology model of the alogliptin-glucose control system to predict plasma exposure and use glucose as a clinical endpoint to prospectively understand its therapeutic outcomes with varying renal function. Our model incorporates a PBPK model for alogliptin, DPP-4 activity described by receptor occupancy theory, and the crosstalk and feedback loops for GLP-1-GIP-glucagon, insulin, and glucose.
View Article and Find Full Text PDFCancer Chemother Pharmacol
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Clinical Pharmacology & Quantitative Pharmacology, BioPharmaceuticals R&D, AstraZeneca, Waltham, MA, USA.
Purpose: Durvalumab in combination with gemcitabine/cisplatin has shown a favorable benefit-risk profile in the TOPAZ-1 study for advanced biliary tract cancers (BTC). This analysis evaluated the population pharmacokinetics (PopPK) of durvalumab, and exposure-response for efficacy and safety (ERES) of TOPAZ-1.
Methods: The PopPK model for durvalumab was updated using data from 5 previously analysed studies and TOPAZ-1.
AAPS PharmSciTech
January 2025
Department of Chemistry, Center for Physical and Mathematical Sciences, Federal University of Santa Catarina, Florianópolis, SC, 88040-900, Brazil.
Developing orally administered pediatric formulations presents significant challenges due to the unique characteristics of pediatric patients. Terbinafine hydrochloride (TER), a powerful antifungal agent, is effective against various fungal infections, including Tinea capitis, which is common in children. However, its low aqueous solubility necessitates innovative pharmaceutical strategies to enhance its effectiveness.
View Article and Find Full Text PDFCancer Chemother Pharmacol
January 2025
Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Purpose: Relapsed and/or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome continue to have a poor prognosis with limited treatment options despite advancements in rational combination and targeted therapies. Belinostat (an HDAC inhibitor) and Pevonedistat (a NEDD8 inhibitor) have each been independently studied in hematologic malignancies and have tolerable safety profiles with limited single-agent activity. Preclinical studies in AML cell lines and primary AML cells show the combination to be highly synergistic, particularly in high-risk phenotypes such as p53 mutant and FLT-3-ITD positive cells.
View Article and Find Full Text PDFClin Pharmacokinet
January 2025
Division of Medicines, Department of Pharmacy, Pharmacy Service, Hospital Clinic of Barcelona, Universitat de Barcelona, Barcelona, Spain.
Population pharmacokinetic (popPK) models are an essential tool when implementing therapeutic drug monitoring (TDM) and to overcome dosing challenges in neonates in clinical practice. Since vancomycin, gentamicin, and amikacin are among the most prescribed antibiotics for the neonatal population, we aimed to characterize the popPK models of these antibiotics and the covariates that may influence the pharmacokinetic parameters in neonates and infants with no previous pathologies. We searched the PubMed, Embase, Web of Science, and Scopus databases and the bibliographies of relevant articles from inception to the beginning of February 2024.
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