Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacokinetics and acute toxicity of carmustine (BCNU) have been studied in ten patients receiving high-dose combination chemotherapy with cyclophosphamide, cisplatin, and BCNU as treatment for advanced neoplasms. Patients received from 300 to 750 BCNU mg/m2 of body surface area as a 2-hour infusion. The immediate effects of this schedule of BCNU included tachycardia, hypotension, flushing, confusion, nausea, and vomiting. Hypotension was a prominent feature of high-dose BCNU administration. The pharmacokinetics of high-dose BCNU were studied via serial blood samples obtained during and following BCNU infusion. Concentrations of BCNU in total plasma and ultrafiltrable (bioavailable) plasma were determined by high-pressure liquid chromatography with UV detection. Average pharmacokinetic parameters for bioavailable plasma BCNU, calculated on the basis of a one-compartment model, include an elimination constant of 0.031 min-1 and a volume of distribution of 5.1 L/kg. Average clearance of total plasma BCNU is 77.6 ml/kg/min. When corrected to a constant dose of 1 g/m2, the average peak concentration at the end of the infusion was 7.8 microM and the area under the curve was 538 microM X min. Plasma BCNU was largely (77%) protein bound. The distribution, clearance, and protein binding of high-dose BCNU were similar to those reported for standard-dose BCNU.
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PMID:Pharmacokinetics and immediate effects of high-dose carmustine in man. 371 78

Sixteen patients with intracerebral tumors received intraarterial cisplatin, teniposide, and BCNU combined with intravenous cisplatin, teniposide, and cytosine arabinoside. Oral glycerol and intravenous mannitol were given along with the intravenous chemotherapy in an attempt to increase drug delivery to tumor by augmenting tumor blood flow. Thirteen additional patients were treated with the same regimen, but received all the chemotherapy intravenously. Of the 16 patients receiving intraarterial chemotherapy (median survival, 14 weeks), none responded, 5 (31%) were stable for > 8 weeks, 8 (50%) failed, and 3 (19%) were unevaluable due to early death. Of the 13 patients receiving all their treatment intravenously (median survival, 13 weeks), 3 (23%) responded, 1 (8%) was stable, 7 (54%) failed, and 2 (15%) were unevaluable due to early death. In the patients receiving intraarterial chemotherapy, toxicity included ipsilateral retinal toxicity (2 patients), ocular pain or headache (10), periorbital swelling and flushing (6), increased brain edema with focal neurological deficits and drowsiness (5), and catheter-related carotid artery thrombosis followed by fatal herniation (1). Myelosuppression was worse in patients who received all their treatment intravenously than in those receiving intraarterial chemotherapy (p < 0.05). Neutropenic sepsis developed in 4 patients on the intraarterial arm (1 fatal) and in 5 patients on the intravenous arm (2 fatal). Other toxic effects were similar whether or not patients received intraarterial treatment or only intravenous treatment. Overall, toxicity of this regimen was excessive, and response rates were lower than would have been expected with single agent therapy.
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PMID:Feasibility study of intraarterial vs intravenous cisplatin, BCNU, and teniposide combined with systemic cisplatin, teniposide, cytosine arabinoside, glycerol and mannitol in the treatment of primary and metastatic brain tumors. 812 May 74

We describe seven patients who developed symptoms including severe headache, circumoral paresthesia, and facial flushing during high-dose carmustine (BCNU) infusion as part of the preparative regimen for autologous peripheral blood stem cell (PBSC) transplantation for metastatic breast cancer. Five patients responded to pain medications, including partial and complete opiate receptor agonists. Premedication of subsequent doses of BCNU with corticosteroids, pain medications, or benzodiazepines lessened, but did not prevent the same symptoms from recurring. The incidence and mechanism of this toxicity are unknown, but this adverse syndrome should be considered when administering high-dose BCNU infusions.
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PMID:Headache, circumoral paresthesia, and facial flushing associated with high-dose carmustine infusion. 913 80