Evaluation of the effects of ontogenetic or maturation functions and chronic heart failure on the model analysis for the dose-response relationship of warfarin in Japanese children

Tamura, Rika; Watanabe, Nao; Nakamura, Saki; Yoshimura, Naoki; Ozawa, Sayaka; Hirono, Keiichi; Ichida, Fukiko; Taguchi, Masato

doi:10.1007/s00228-019-02652-x

Cited by 1 publication

(3 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dose is the daily dose of warfarin (mg/d), SIZE is the hypothetical body size, WT is the individual body weight in kg and 0.559 is the allometric index value reported in our previous study. 7) Calculation of Estimated Glomerular Filtration Rate (eGFR) The eGFR value was calculated by using the Schwartz formula. 11)…”

Section: Anticoagulant Index :Pt-inr /(Dose /Size)mentioning

confidence: 99%

“…We previously demonstrated that the rational pediatric dosage of warfarin can be welldescribed by a body size (SIZE) parameter that includes an allometry exponent of weight. 6,7) The SIZE parameter is useful to describe the response to warfarin in pediatric patients. We encountered the interaction between warfarin and rifampicin via PXR in a pediatric patient with congenital heart disease in whom rifampicin was used for infective endocarditis (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…9) We previously reported that the combined administration of bosentan reversibly reduced the warfarin anticoagulant effects to 87.5% in pediatric patients. 6,7) Thus, we proposed paying attention to the changes in response to warfarin after the withdrawal of bosentan or switching to other drugs. On the other hand, the PXR activation effects of macitentan are thought to be negligible in clinical settings because the EC 50 value for PXR activation is higher than the therapeutic plasma concentrations of macitentan.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of Concomitant Administration of PXR Ligand Drugs on the Anticoagulant Effects of Warfarin

Mito

Hirono

Ide

et al. 2022

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

We encountered cases in which the anticoagulant effects of warfarin (CYP2C9 substrate) were reversibly attenuated by the concomitant administration of rifampicin or bosentan, which are potent pregnane X receptor (PXR) ligands. The purpose of the present study is to report the previous case with rifampicin, and to evaluate the changes in the warfarin anticoagulant effects when withdrawing or switching bosentan treatment. The former is a case study of a 4-year-old girl undergoing warfarin treatment. The latter is a longitudinal study of 20 pediatric patients receiving stable warfarin treatment. The prothrombin time and international normalized ratio (PT-INR) values were extracted from the medical records and normalized by the daily-dose per body size as an index for the warfarin anticoagulant effects. Rifampicin treatment resulted in a 52.0% decrease in the anticoagulant index. On the other hand, 10 of 20 patients started bosentan and their anticoagulant index was reduced by a median of 2.00. Bosentan was withdrawn in 4 of 20 patients and their anticoagulant index increased by a median of 3.67. Six of 20 patients switched from bosentan to macitentan, which is considered not to activate PXR in clinical settings. However, switching from bosentan to macitentan resulted in a median of 2.25 reduction of the anticoagulant index rather than recovery of the response to warfarin. This study suggests not only the possibility of heterogeneity in the response to PXR activation and deactivation, but also the importance of long-term monitoring of drug-drug interactions when switching from bosentan to macitentan.

show abstract

Section: Anticoagulant Index :Pt-inr /(Dose /Size)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%