Background And Objective: Pazopanib is an oral tyrosine kinase inhibitor used in the treatment of renal cell carcinoma and soft-tissue sarcoma. At the approved dose of 800 mg once daily (QD), 16-20% of patients are being underdosed and at risk of decreased efficacy. This study aimed to show whether splitting intake moments, as a cost-neutral alternative to a dose increase, leads to an increased exposure.
Methods: We performed a cross-over trial comparing the pharmacokinetics of pazopanib 800 mg QD with pazopanib 400 mg twice daily. Pharmacokinetic sampling was performed at steady-state for both dosing schedules.
Results: Nine evaluable patients were included. At the 800 mg QD dosing schedule, median minimum plasma concentration (C), area under the concentration-time curve from 0 to 24 h (AUC), and maximum plasma concentration (C) were 23.2 mg/L (interquartile range 18.5-27.6), 773 mg h/L (557-1009), and 40.6 mg/L (36.4-56.4) compared with 41.6 mg/L (30.5-55.8, p = 0.004), 942 mg h/L (885-1419, p = 0.027), and 50.2 mg/L (46.8-72.5, p = 0.074) at 400 mg twice daily. One patient experienced a grade 3 event (i.e., diarrhea).
Conclusions: This study demonstrates that splitting intake moments of pazopanib leads to a 79% increase in C, with acceptable tolerability. Therefore, this new dosing schedule offers a cost-neutral opportunity to optimize treatment in patients with low exposure.
Clinical Trial Registration: NL6137 ( http://www.trialregister.nl ).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s40262-020-00863-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Impact of protein intake from a caloric-restricted diet on liver lipid metabolism in overweight and obese rats of different sexes.
Sci Rep
January 2025
Department of Cuisine and Nutrition, School of Tourism and Cuisine, Yangzhou University, Yangzhou, China.
In addition to being linked to an excess of lipid accumulation in the liver, being overweight or obese can also result in disorders of lipid metabolism. There is limited understanding regarding whether different levels of protein intake within an energy-restricted diet affect liver lipid metabolism in overweight and obese rats and whether these effects differ by gender, despite the fact that both high protein intake and calorie restriction can improve intrahepatic lipid. The purpose of this study is to explore the effects and mechanisms of different protein intakes within a calorie-restricted diet on liver lipid metabolism, and to investigate whether these effects exhibit gender differences.
View Article and Find Full Text PDFAssociation between serum 25-hydroxyvitamin D concentrations and urinary vitamin D metabolite concentrations measured by the NLucVDR assay.
J Steroid Biochem Mol Biol
January 2025
Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan. Electronic address:
It is well known that vitamin D is essential for human health; however, many people suffer from vitamin D deficiency or insufficiency worldwide, including in Japan. Serum 25-hydroxyvitamin D (25(OH)D) concentrations are typically measured to evaluate vitamin D status. In a previous study, we demonstrated that the concentrations of vitamin D metabolites in urine, measured using the NLucVDR assay system composed of a split-type nanoluciferase and the ligand-binding domain (LBD) of the human vitamin D receptor, correlated with serum 25(OH)D concentrations measured using liquid chromatography-mass spectrometry (LC-MS) or electrochemiluminescence immunoassays (ECLIAs).
View Article and Find Full Text PDFEffects of including a palmitic acid-enriched supplement in low and high starch diets on milk production and energy partitioning of primiparous and multiparous dairy cows between mid and late-lactation.
J Dairy Sci
January 2025
Department of Animal Science, Michigan State University, East Lansing, MI 48824. Electronic address:
The aim of our study was to assess the effects of low or high-starch diets with or without palmitic acid (C16:0) supplementation on the yield of milk, milk components, and energy partitioning of primiparous and multiparous dairy cows between mid and late-lactation. Thirty-two Holstein cows, 12 primiparous ([mean ± SD] 163 ± 33 d in milk) and 20 multiparous ([mean ± SD] 179 ± 37 d in milk), were used in a split-plot Latin square design. Parity was considered the main plot, and within each plot, treatments were then randomly assigned in a replicated 4 × 4 Latin square with 21 d periods and balanced for carryover effects.
View Article and Find Full Text PDFReducing Dietary Protein Levels with Amino Acid Supplementation in Duroc Sire Line Finishing Pigs: Growth Performances, Carcass and Meat Traits and Nitrogen Balance in Males and Females.
Animals (Basel)
December 2024
Departamento de Producción Animal y Ciencia de los Alimentos, Escuela Politécnica Superior, Universidad de Zaragoza, Carretera de Cuarte s/n, 22071 Huesca, Spain.
Crude protein (CP) reduction and amino acid (AAs) supplementation is an interesting cost-reducing strategy for environmental compliance. The objective of this work is to study productive performances of heavy Duroc X (Landrace X Large white) male and female pigs during the finishing stage under a 2% CP reduction with crystalline AA supplementation. A total of 60 entire male and 60 female pigs (means ± standard deviations: 109 ± 4.
View Article and Find Full Text PDFParticle size of wheat straw from genetically improved wheat affects the production performance and feeding behavior of Sahiwal cows.
Trop Anim Health Prod
January 2025
Sub Campus T.T Singh, University of Agriculture Faisalabad, Faisalabad, 38040, Pakistan.
The current study was designed to evaluate the effect of particle size (PS) and inclusion level of wheat straw (WS) obtained from genetically improved wheat on the performance and feeding behavior of Sahiwal cows. Twelve multiparous, mid-lactating Sahiwal cows (DIM 135 ± 25, mean ± SD; 12.8 ± 1.
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!