ArticleClinical drug investigation2023
Effect of Daridorexant on the Pharmacokinetics of P-Glycoprotein Substrate Dabigatran Etexilate and Breast Cancer Resistance Protein Substrate Rosuvastatin in Healthy Subjects.
Article in Clinical drug investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05480475 (A Single-center, Open-label, Three-period, Fixed-sequence Design Study to Investigate the Effect of Daridorexant on the Pharmacokinetics of Dabigatran and Rosuvastatin in Healthy Male Subjects), which is not on this map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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A Single-center, Open-label, Three-period, Fixed-sequence Design Study to Investigate the Effect of Daridorexant on the Pharmacokinetics of Dabigatran and Rosuvastatin in Healthy Male Subjects
Who cites it
1 citing paper in PubMed, 2 citations in OpenAlex.
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4 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveThe dual orexin receptor antagonist daridorexant was approved in 2022 for the treatment of insomnia at doses up to 50 mg once per night. This study aimed at investigating the effect of daridorexant 50 mg at steady state on the pharmacokinetics of dabigatran, the active moiety of dabigatran etexilate, and rosuvastatin, sensitive substrates of P-glycoprotein and breast cancer resistance protein, respectively.
methodsThis single-center, open-label, fixed-sequence study enrolled 24 healthy male subjects who were dosed orally with dabigatran etexilate 75 mg on days 1 (Treatment A1) and 9 (Treatment C1) as well as rosuvastatin 10 mg on days 3 (Treatment A2) and 11 (Treatment C2). On days 7-14, daridorexant (50 mg once daily) was administered. Blood samples for the pharmacokinetics of both substrates and the pharmacodynamics of dabigatran, i.e., two coagulation tests, were collected and safety assessments performed. Noncompartmental pharmacokinetic parameters and pharmacodynamic variables were evaluated with geometric mean ratios and 90% confidence intervals of Treatment C1/C2 versus A1/A2.
resultsGeometric mean ratios (90% confidence interval) of dabigatran maximum plasma concentration and area under the plasma concentration-time curve were 1.3 (1.0-1.7) and 1.4 (1.1-1.9), respectively, whereas the time to maximum plasma concentration and terminal half-life were comparable between treatments. Pharmacodynamic variables showed a similar pattern as dabigatran pharmacokinetics in both treatments. Rosuvastatin pharmacokinetics were unchanged upon concomitant daridorexant administration. All treatments were well tolerated.
conclusionsA mild inhibition of P-glycoprotein was observed after administration of daridorexant (50 mg once daily) at steady state, whereas breast cancer resistance protein was not affected. CLINICAL
trial registrationNCT05480475; date of registration: 29 July, 2022.
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