Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A single-dose study was conducted to determine concentrations of trovafloxacin (CP-99,219) achieved in the cerebrospinal fluid (CSF) relative to those in the serum of healthy subjects after intravenous infusion of alatrofloxacin (CP-116,517), the alanyl-alanyl prodrug of trovafloxacin. Twelve healthy subjects were administered single doses of alatrofloxacin at a trovafloxacin equivalent of 300 mg as an intravenous infusion over 1.0 h. CSF samples were taken by lumbar puncture at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 24 h after the start of the infusion; each subject was sampled at only one time point. Serum samples were taken from each subject at the time of CSF collection. A mean concentration of 5.8 microg of trovafloxacin per ml was present in serum 1.0 h after the start of the infusion. CSF/serum ratios ranged from 0.14 to 0.33 in the postdistribution phase (5 to 24 h postinfusion), with a mean ratio of 0.25. The most common adverse events were dizziness, nausea, and rash and were mild or moderate in intensity. The potency of trovafloxacin against susceptible organisms, coupled with its rapid penetration of CSF following the intravenous administration of alatrofloxacin, suggests that it may be useful in the treatment of bacterial meningitis in humans.
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PMID:Penetration of trovafloxacin into cerebrospinal fluid in humans following intravenous infusion of alatrofloxacin. 917 87

CEP-2563 dihydrochloride (CEP-2563) is a soluble lysinyl-beta-alanyl ester of CEP-751, a potent inhibitor of the trk family of receptor tyrosine kinases and the platelet-derived growth factor (PDGF) receptor tyrosine kinase. CEP-2563 was developed because of the limited aqueous solubility of CEP-751. Preclinical models have demonstrated that both CEP-751 and CEP-2563 have antitumor activity in a variety of tumors. A Phase I clinical trial involving 18 patients was conducted to determine the toxicity profile, maximum tolerated dose (MTD), toxicity profile, and pharmacokinetics of CEP-2563 in patients with advanced solid tumors refractory to standard therapy. CEP-2563 was administered over 1 hour via a central venous catheter once daily for five consecutive days every three weeks. A rapid dose titration strategy with initial single patient cohorts and 100% dose escalations was used. With the appearance of drug-related toxicity, escalations were decreased to 50% or 25% and cohorts were expanded to 3 or 6 patients until establishment of the MTD. Dose escalation rapidly proceeded to 320 mg/m(2)/d. The dose limiting toxicities (DLTs) observed were grade 3 hypotension and grade 2 allergic reaction. Other toxicities included anemia, thrombocytopenia, anorexia, asthenia, diarrhea, fatigue, headache, nausea, vomiting, and rash. Pharmacokinetic analysis showed that CEP-2563 is reliably converted to CEP-751. This study demonstrated that single agent CEP-2563 therapy is feasible with acceptable toxicities. The recommended phase II dose is 256 mg/m(2)/d. Rapid dose escalation with single patient cohorts was a safe and efficient method of conducting this phase I trial.
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PMID:Phase I clinical trial of CEP-2563 dihydrochloride, a receptor tyrosine kinase inhibitor, in patients with refractory solid tumors. 1529 15