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

N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine.HCl (DPPE) is a diphenylmethane analog of tamoxifen that antagonizes the intracellular binding of histamine to growth-regulatory sites, a proportion of which represents P450 enzymes, in microsomes and nuclei. We previously reported increased response rates and decreased myelotoxicity in patients with prostate and other cancers who received an intensive dose/schedule of DPPE plus single-agent chemotherapy. We now report the results of a study of DPPE combined with a standard dose/schedule of doxorubicin in twenty-three patients with metastatic breast cancer, sixteen of whom had received prior non-anthracycline chemotherapy. DPPE (6 mg/kg) was infused intravenously (i.v.) over 80 minutes. Doxorubicin (60 mg/m2) was administered i.v. over the last 20 minutes of the DPPE infusion. Treatment was repeated every 3 weeks (maximum, 7 cycles). Patients achieving complete response (CR) were followed off treatment until relapse. All patients were evaluable for toxicities and efficacy. Sixteen patients (69%; 95% C.I. = 47-87%) responded (7 CR and 9 PR). Eleven responders, including 6 with CR, had prior chemotherapy. Five responders (2CR, 3PR) had a poor (ECOG 3/4) performance status pre-treatment. Median CR duration was 11 (range 5-18) months. Hematological toxicity was low; GI toxicity (nausea/vomiting/dyspepsia) appeared somewhat higher than historical experience, but responded well to anti-emetics, ranitidine, and/or dexamethasone in most patients; a mean absolute drop in left ventricular ejection fraction of 8% occurred in 17 patients who received = or > 300 mg/m2 doxorubicin. The observed response rate in DPPE/doxorubicin-treated patients appeared to be higher than historically reported for doxorubicin alone in this setting, suggesting a chemopotentiating effect of DPPE. A multi-centre trial of this regimen in an additional 32 patients with early metastatic breast cancer has been conducted by the Clinical Trials Group, National Cancer Institute of Canada, and a phase 3 study is planned.
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PMID:The intracellular histamine antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethamine.HCL, may potentiate doxorubicin in the treatment of metastatic breast cancer: Results of a pilot study. 969 12

There are no Food and Drug Administration (FDA)-approved antimicrobial agents for use in cultured American alligators (Alligator mississippiensis) destined for human consumption yet some producers administer antibiotics for prophylaxis. The cytochromes P450-dependent mixed-function oxygenases (MFO) catalyze the oxidation of xenobiotic compounds such as drugs, pesticides and polycyclic aromatic hydrocarbons. Herein, we describe the effects of oxytetracycline, ceftazidime and enrofloxacin on the MFO system of the American alligator, Alligator mississippiensis. Juvenile alligators (4 animals/treatment) were administered these antibiotics intraperitoneally in an effort to induce hepatic microsomal cytochromes P450. Alligators treated with enrofloxacin exhibited emesis and convulsive spasms within 5 min of the initial injection. Total hepatic cytochromes P450 contents were significantly decreased in oxytetracycline-and enrofloxacin-pretreated alligators. In vitro hepatic microsomal benzyloxyresorufin O-dealkylase (BROD) activity was significantly decreased by enrofloxacin pretreatment. Western blots of proteins from antibiotic-pretreated alligator hepatic microsomes incubated with several mammalian and fish cytochromes P450 (CYP) antibodies exhibited little or no induction of CYP1A1, 2B, 2C and 2E1. In vitro incubation with enrofloxacin and oxytetracycline caused a concentration-dependent decrease in alkyl-substituted phenoxazone dealkylase activities catalyzed by phenobarbital- and 3-methylcholanthrene-induced alligator hepatic microsomes.
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PMID:Antibiotic effects on cytochromes P450 content and mixed-function oxygenase (MFO) activities in the American alligator, Alligator mississippiensis. 973 49

Exatecan mesylate (DX-8951f) is a new hexacyclic camptothecin analogue with favorable attributes compared to topotecan and CPT-11, including watersolubility, greater potency against topoisomerase I, lack of esterase-dependent activation, broad antitumor activity, and low cross-resistance against MDR-1 overexpressing tumors. In preclinical studies, the compound demonstrated a favorable toxicology profile with hematologic dose-limiting toxicity and moderate gastrointestinal toxicity, linear pharmacokinetics, P450 hepatic metabolism (CYP3A4 and CYP1A2), and predominately fecal excretion. The results of six U.S. and European phase I clinical trials as well as two Japanese studies are presented including total DX-8951 and lactone DX-8951 pharmacokinetics. The toxicity profile was similar for all schedules of administration. Hematologic toxicity was dose-dependent and reversible. Neutropenia was dose-limiting in minimally pretreated patients, whereas neutropenia and thrombocytopenia were dose-limiting in heavily pretreated patients. Non-hematologic toxicity included moderate gastrointestinal toxicity (nausea, vomiting > diarrhea), transient elevation of hepatic transaminases, asthenia, and alopecia. Two cases of acute pancreatitis not predicted by preclinical toxicology were also observed. Antineoplastic activity was detected in several solid tumor types: non-small cell lung cancer, extrapulmonary small cell cancer, colorectal cancer, hepatocellular cancer, and sarcoma. Antitumor activity was seen in CPT-11 and topotecan-resistant tumors. Pharmacokinetics were linear within the dose range tested. A pharmacokinetic/pharmacodynamic model predictive of DX-8951f-induced neutropenia in individual patients was developed. The daily x5, every 3-week schedule with the drug administered as a 30-minute intravenous infusion was selected for future phase II clinical trials based on its superior antitumor activity.
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PMID:DX-8951f: summary of phase I clinical trials. 1119 1