Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two groups of 8 monkeys were anesthetized with either BAX-3224, a new fluorinated methyl-propyl ether, or with halothane, 3 hours daily for a total of 30 hours. Vomiting incidence was 12.5 percent with BAX-3224 during both induction and recovery, compared with 3.7 percent for halothane during induction and 7 percent for halothane during recovery. Induction time did not change during the course of study with either agent. Respiration was spontaneous and cardiopulmonary function was stable. Electroretinographic (ERG) responses were consistent, flicker-light responses similar, but visual evoked responses (VER) were not present during BAX-3224 anesthesia. A 33 percent incidence of electroencephalographic (EEG) silence occurred with BAX-3224, which was consistent with absence of VER. Hematologic and serum chemistry values were similar for both agents. Serum fluoride ion concentrations, measured before exposure and 4 times during the 10-day study, did not change after administration of either agent. This finding was significant for BAX-3224, a fluorinated ether. No cardiac arrhythmias were observed during BAX-3224 anesthesia, compared with a 17 percent incidence during halothane induction. Recovery time was 32 minutes following BAX-3224 and 14 minutes after halothane. BAX-3224 produced anesthesia similar to that of halothane, did not induce changes incompatible with recovery from anesthesia, and showed great potential as a new volatile liquid anesthetic agent with excellent biologic stability.
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PMID:Comparative evaluation of a new inhalation anesthetic, BAX-3224, and halothane in Macaca speciosa. 23 98

This open-label, phase 1 study evaluated the safety, pharmacokinetics, and maximum tolerated dose of AMG 232, an investigational oral, selective mouse double minute 2 homolog inhibitor in relapsed/refractory acute myeloid leukemia (AML). AMG 232 was administered orally once daily for 7 days every 2 weeks (7 on/off) at 60, 120, 240, 360, 480, or 960 mg as monotherapy (arm 1) or at 60 mg with trametinib 2 mg (arm 2). Dose-limiting toxicities (DLTs), adverse events (AEs), pharmacokinetics, clinical and pharmacodynamic response, and expression of p53 target genes were assessed. All 36 patients received AMG 232. No DLTs occurred in arm 1, and 360 mg was the highest test dose; dose escalation was halted due to gastrointestinal AEs at higher doses. One of ten patients in arm 2 had a DLT (grade 3 fatigue); 60 mg was the highest dose tested with trametinib. Common treatment-related AEs (any grade) included nausea (58%), diarrhea (56%), vomiting (33%), and decreased appetite (25%). AMG 232 exhibited linear pharmacokinetics unaffected by coadministration with trametinib. Serum macrophage inhibitor cytokine-1 and bone marrow expression of BAX, PUMA, P21, and MDM2 increased during treatment. Of 30 evaluable patients, 1 achieved complete remission, 4 had morphologic leukemia-free state, and 1 had partial remission. Four of 13 (31%) TP53-wild-type patients and 0 of 3 (0%) TP53-mutant patients were responders. AMG 232 was associated with gastrointestinal AEs at higher doses but had acceptable pharmacokinetics, on-target effects, and promising clinical activity warranting further investigation in patients with relapsed/refractory AML. This trial was registered at www.clinicaltrials.gov as #NCT02016729.
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PMID:Phase 1b study of the MDM2 inhibitor AMG 232 with or without trametinib in relapsed/refractory acute myeloid leukemia. 3125 96