FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2912785940> ?p ?o ?g. }

• W2912785940 endingPage "S357" @default.
• W2912785940 startingPage "S357" @default.
• W2912785940 abstract "IntroductionRezafungin (RZF) is a new echinocandin being developed to treat patients with systemic fungal infections and to prevent invasive fungal infections in allogeneic hematopoietic stem cell transplant (HSCT) recipients and other patients at high risk of infection. RZF is differentiated by stable and efficacy-driving pharmacokinetics (PK) that allow for once-weekly dosing. Several in vitro studies have been conducted to assess the potential for rezafungin to alter the PK of other drugs. Based on the results, possible interactions were identified in which the risk of drug-drug interactions (DDIs) could not be ruled out relative to the assumed Ph3 dose of 400 mg once weekly and known PK exposure in healthy subjects. Clinical in vivo evaluations of drug interaction potential were performed proactively.MethodsThis was an open-label, inpatient study of 26 healthy subjects to assess DDIs between RZF and probe drugs selected for known interactions with CYP enzymes and transporters (and consequently commonly used in evaluations of PK interaction), as well as drugs likely to be coadministered with RZF. A loading dose of RZF 600 mg was administered on the first dosing day, to approximate a steady state plasma concentration of multiple once-weekly 400-mg doses, followed by 400-mg doses on days 10 and 15. Probe drugs were administered as part of a cocktail containing ≥2 drugs, once prior to and once after receiving RZF on a schedule designed to allow for washout between doses and to limit interactions with other drugs (Figure 1).Samples were analyzed to determine RZF, tacrolimus, repaglinide, metformin, rosuvastatin, pitavastatin, caffeine, efavirenz, midazolam and digoxin concentrations in plasma (except for tacrolimus which was in whole blood) to characterize the PK profile of each analyte. PK exposure parameters (area under curve [AUC] and maximum concentration [Cmax]) were calculated from the plasma concentration-time profiles by noncompartmental analysis.ResultsWhen rezafungin was dosed concomitantly with metformin, pitavastatin, caffeine, efavirenz, midazolam, digoxin, tacrolimus, repaglinide, and rosuvastatin, no relevant change in systemic concentrations of these probe drugs was observed (Figure 2).PK exposure of all drugs were similar with or without RZF. Maximum changes in mean Cmax or AUC were <25% for all drugs when given with or without RZF and unlikely to be clinically signficant.ConclusionNo meaningful PK interactions occurred between RZF and the 9 probe drug substrates tested, providing evidence that no RZF dose adjustment is expected when co-administered with these commonly used drugs. Rezafungin (RZF) is a new echinocandin being developed to treat patients with systemic fungal infections and to prevent invasive fungal infections in allogeneic hematopoietic stem cell transplant (HSCT) recipients and other patients at high risk of infection. RZF is differentiated by stable and efficacy-driving pharmacokinetics (PK) that allow for once-weekly dosing. Several in vitro studies have been conducted to assess the potential for rezafungin to alter the PK of other drugs. Based on the results, possible interactions were identified in which the risk of drug-drug interactions (DDIs) could not be ruled out relative to the assumed Ph3 dose of 400 mg once weekly and known PK exposure in healthy subjects. Clinical in vivo evaluations of drug interaction potential were performed proactively. This was an open-label, inpatient study of 26 healthy subjects to assess DDIs between RZF and probe drugs selected for known interactions with CYP enzymes and transporters (and consequently commonly used in evaluations of PK interaction), as well as drugs likely to be coadministered with RZF. A loading dose of RZF 600 mg was administered on the first dosing day, to approximate a steady state plasma concentration of multiple once-weekly 400-mg doses, followed by 400-mg doses on days 10 and 15. Probe drugs were administered as part of a cocktail containing ≥2 drugs, once prior to and once after receiving RZF on a schedule designed to allow for washout between doses and to limit interactions with other drugs (Figure 1). Samples were analyzed to determine RZF, tacrolimus, repaglinide, metformin, rosuvastatin, pitavastatin, caffeine, efavirenz, midazolam and digoxin concentrations in plasma (except for tacrolimus which was in whole blood) to characterize the PK profile of each analyte. PK exposure parameters (area under curve [AUC] and maximum concentration [Cmax]) were calculated from the plasma concentration-time profiles by noncompartmental analysis. When rezafungin was dosed concomitantly with metformin, pitavastatin, caffeine, efavirenz, midazolam, digoxin, tacrolimus, repaglinide, and rosuvastatin, no relevant change in systemic concentrations of these probe drugs was observed (Figure 2). PK exposure of all drugs were similar with or without RZF. Maximum changes in mean Cmax or AUC were <25% for all drugs when given with or without RZF and unlikely to be clinically signficant. No meaningful PK interactions occurred between RZF and the 9 probe drug substrates tested, providing evidence that no RZF dose adjustment is expected when co-administered with these commonly used drugs." @default.
• W2912785940 created "2019-02-21" @default.
• W2912785940 creator A5001728425 @default.
• W2912785940 creator A5056848374 @default.
• W2912785940 creator A5090249918 @default.
• W2912785940 date "2019-03-01" @default.
• W2912785940 modified "2023-09-24" @default.
• W2912785940 title "No Relevant Pharmacokinetic (PK) Interaction between Rezafungin and Nine Probe Drugs: Results from a Drug-Drug Interaction (DDI) Study" @default.
• W2912785940 doi "https://doi.org/10.1016/j.bbmt.2018.12.579" @default.
• W2912785940 hasPublicationYear "2019" @default.
• W2912785940 type Work @default.
• W2912785940 sameAs 2912785940 @default.
• W2912785940 citedByCount "5" @default.
• W2912785940 countsByYear W29127859402019 @default.
• W2912785940 countsByYear W29127859402021 @default.
• W2912785940 countsByYear W29127859402022 @default.
• W2912785940 crossrefType "journal-article" @default.
• W2912785940 hasAuthorship W2912785940A5001728425 @default.
• W2912785940 hasAuthorship W2912785940A5056848374 @default.
• W2912785940 hasAuthorship W2912785940A5090249918 @default.
• W2912785940 hasBestOaLocation W29127859401 @default.
• W2912785940 hasConcept C112705442 @default.
• W2912785940 hasConcept C150903083 @default.
• W2912785940 hasConcept C207001950 @default.
• W2912785940 hasConcept C2777288759 @default.
• W2912785940 hasConcept C2780035454 @default.
• W2912785940 hasConcept C71924100 @default.
• W2912785940 hasConcept C86803240 @default.
• W2912785940 hasConcept C97320921 @default.
• W2912785940 hasConcept C98274493 @default.
• W2912785940 hasConceptScore W2912785940C112705442 @default.
• W2912785940 hasConceptScore W2912785940C150903083 @default.
• W2912785940 hasConceptScore W2912785940C207001950 @default.
• W2912785940 hasConceptScore W2912785940C2777288759 @default.
• W2912785940 hasConceptScore W2912785940C2780035454 @default.
• W2912785940 hasConceptScore W2912785940C71924100 @default.
• W2912785940 hasConceptScore W2912785940C86803240 @default.
• W2912785940 hasConceptScore W2912785940C97320921 @default.
• W2912785940 hasConceptScore W2912785940C98274493 @default.
• W2912785940 hasIssue "3" @default.
• W2912785940 hasLocation W29127859401 @default.
• W2912785940 hasOpenAccess W2912785940 @default.
• W2912785940 hasPrimaryLocation W29127859401 @default.
• W2912785940 hasRelatedWork W1990964652 @default.
• W2912785940 hasRelatedWork W2049819497 @default.
• W2912785940 hasRelatedWork W2071747460 @default.
• W2912785940 hasRelatedWork W2104446368 @default.
• W2912785940 hasRelatedWork W2227061539 @default.
• W2912785940 hasRelatedWork W2325795327 @default.
• W2912785940 hasRelatedWork W2588064125 @default.
• W2912785940 hasRelatedWork W2889241014 @default.
• W2912785940 hasRelatedWork W2912785940 @default.
• W2912785940 hasRelatedWork W4205993769 @default.
• W2912785940 hasVolume "25" @default.
• W2912785940 isParatext "false" @default.
• W2912785940 isRetracted "false" @default.
• W2912785940 magId "2912785940" @default.
• W2912785940 workType "article" @default.