FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W46526311> ?p ?o ?g. }

• W46526311 endingPage "3057" @default.
• W46526311 startingPage "3057" @default.
• W46526311 abstract "3057 Background: CI-1033 is a pan-erbB tyrosine kinase inhibitor. In phase 1 oral (PO) studies, dose limiting toxicities were primarily gastrointestinal (GI), which supported the exploration of IV dosing to achieve higher drug exposures. Methods: Forty-eight patients (pts) with advanced nonhematologic malignancies received IV CI-1033 via 30 min infusions (10–500 mg) on a 3-day weekly (MWF) schedule. PK samples were collected on Days 1 and 8 and evaluated using compartmental analysis (NONMEM ADVAN3). Results: 28M/20F, ECOG PS 0 & 1, median age 54 (42–73), tumors: lung 11, colorectal 10, mesothelioma 9, melanoma 4, unknown primary 2, others 12. Despite a 5 to 10-fold increase in IV Cmax and a 3-fold increase in AUC compared to PO at equivalent doses, treatment-related GI AEs were notably less frequent with this IV regimen than with once weekly dosing of PO CI-1033 (100–1000 mg; n=55; Proc. ASCO 2001,283:72a). The incidences of the most common GI AEs when given IV were Gr 1–2 nausea (15%), vomiting (11%), diarrhea (7%) vs 60%, 40%, and 49%, respectively, with PO dosing. Whereas Gr 3 GI AEs occurred in 2% of pts on the PO study, none were reported in the IV study to date. The incidences of Gr 3 hypersensitivity were comparable for IV and PO regimens (each 2%). Systemic exposure was dose proportional with bi-phasic elimination. The initial distribution phase had a 2 to 3 minute half-life while the terminal elimination phase half-life was approx 3 hrs. Central volume of distribution (18.5 liters) approximated extravascular water volume. Systemic clearance was rapid at 3 L/min. Systemic exposure was not dependent upon age, gender, race, renal function, body weight or surface area in this IV study. Conclusions: Gastrointestinal AEs were less frequent following IV dosing relative to PO dosing at comparable systemic exposures and hence higher drug exposures could be acheived by the IV route. Oral bioavailability of CI-1033 is about one-third that observed following IV dosing. The clinical significance of the higher drug exposures achieved by the IV route is yet to be determined but warrants further investgation. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer" @default.
• W46526311 created "2016-06-24" @default.
• W46526311 creator A5004546542 @default.
• W46526311 creator A5021617351 @default.
• W46526311 creator A5023878438 @default.
• W46526311 creator A5024946496 @default.
• W46526311 creator A5039144013 @default.
• W46526311 creator A5041062966 @default.
• W46526311 creator A5048726993 @default.
• W46526311 creator A5049076838 @default.
• W46526311 creator A5057204740 @default.
• W46526311 creator A5060651469 @default.
• W46526311 date "2004-07-15" @default.
• W46526311 modified "2023-10-14" @default.
• W46526311 title "Phase I pharmacokinetic (PK) and safety study of intravenous (IV) CI-1033 in patients with advanced solid tumors" @default.
• W46526311 doi "https://doi.org/10.1200/jco.2004.22.90140.3057" @default.
• W46526311 hasPublicationYear "2004" @default.
• W46526311 type Work @default.
• W46526311 sameAs 46526311 @default.
• W46526311 citedByCount "1" @default.
• W46526311 crossrefType "journal-article" @default.
• W46526311 hasAuthorship W46526311A5004546542 @default.
• W46526311 hasAuthorship W46526311A5021617351 @default.
• W46526311 hasAuthorship W46526311A5023878438 @default.
• W46526311 hasAuthorship W46526311A5024946496 @default.
• W46526311 hasAuthorship W46526311A5039144013 @default.
• W46526311 hasAuthorship W46526311A5041062966 @default.
• W46526311 hasAuthorship W46526311A5048726993 @default.
• W46526311 hasAuthorship W46526311A5049076838 @default.
• W46526311 hasAuthorship W46526311A5057204740 @default.
• W46526311 hasAuthorship W46526311A5060651469 @default.
• W46526311 hasConcept C112705442 @default.
• W46526311 hasConcept C126322002 @default.
• W46526311 hasConcept C197934379 @default.
• W46526311 hasConcept C22979827 @default.
• W46526311 hasConcept C2777288759 @default.
• W46526311 hasConcept C2778496288 @default.
• W46526311 hasConcept C2780580376 @default.
• W46526311 hasConcept C2780852908 @default.
• W46526311 hasConcept C2781413609 @default.
• W46526311 hasConcept C29730261 @default.
• W46526311 hasConcept C71924100 @default.
• W46526311 hasConcept C90924648 @default.
• W46526311 hasConceptScore W46526311C112705442 @default.
• W46526311 hasConceptScore W46526311C126322002 @default.
• W46526311 hasConceptScore W46526311C197934379 @default.
• W46526311 hasConceptScore W46526311C22979827 @default.
• W46526311 hasConceptScore W46526311C2777288759 @default.
• W46526311 hasConceptScore W46526311C2778496288 @default.
• W46526311 hasConceptScore W46526311C2780580376 @default.
• W46526311 hasConceptScore W46526311C2780852908 @default.
• W46526311 hasConceptScore W46526311C2781413609 @default.
• W46526311 hasConceptScore W46526311C29730261 @default.
• W46526311 hasConceptScore W46526311C71924100 @default.
• W46526311 hasConceptScore W46526311C90924648 @default.
• W46526311 hasIssue "14_suppl" @default.
• W46526311 hasLocation W465263111 @default.
• W46526311 hasOpenAccess W46526311 @default.
• W46526311 hasPrimaryLocation W465263111 @default.
• W46526311 hasRelatedWork W2015416409 @default.
• W46526311 hasRelatedWork W2051764329 @default.
• W46526311 hasRelatedWork W2074629895 @default.
• W46526311 hasRelatedWork W2151288869 @default.
• W46526311 hasRelatedWork W2156337883 @default.
• W46526311 hasRelatedWork W2375012438 @default.
• W46526311 hasRelatedWork W2378568667 @default.
• W46526311 hasRelatedWork W2382265168 @default.
• W46526311 hasRelatedWork W2385131479 @default.
• W46526311 hasRelatedWork W2414579301 @default.
• W46526311 hasVolume "22" @default.
• W46526311 isParatext "false" @default.
• W46526311 isRetracted "false" @default.
• W46526311 magId "46526311" @default.
• W46526311 workType "article" @default.