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D Noe

Publications and source records attributed to D Noe.

5 recordsLinked to original sources
PubMed2001

A Phase I clinical and pharmacological evaluation of sodium phenylbutyrate on an 120-h infusion schedule.

PURPOSE: Sodium phenylbutyrate (PB) demonstrates potent differentiating capacity in multiple hematopoietic and solid tumor cell lines. We conducted a Phase I and pharmacokinetic study of PB by continuous infusion to characterize the maximum tolerated dose, toxicities, pharmacokinetics, and antitumor effects in patients with refractory solid tumors. PATIENTS AND METHODS: Patients were treated with a 120-h PB infusion every 21 days. The dose was escalated from 150 to 515 mg/kg/day. Pharmacokinetics were performed during and after the first infusion period using a validated high-performance liquid chromatographic assay and single compartmental pharmacokinetic model for PB and its principal metabolite, phenylacetate. RESULTS: A total of 24 patients were enrolled on study, with hormone refractory prostate cancer being the predominant tumor type. All patients were evaluable for toxicity and response. A total of 89 cycles were administered. The dose-limiting toxicity (DLT) was neuro-cortical, exemplified by excessive somnolence and confusion and accompanied by clinically significant hypokalemia, hyponatremia, and hyperuricemia. One patient at 515 mg/kg/day and another at 345 mg/kg/day experienced this DLT. Toxicity resolved < or =12 h of discontinuing the infusion. Other toxicities were mild, including fatigue and nausea. The maximum tolerated dose was 410 mg/kg/day for 5 days. Pharmacokinetics demonstrated that plasma clearance of PB increased in a continuous fashion beginning 24 h into the infusion. In individuals whose V(max) for drug elimination was less than their drug-dosing rate, the active metabolite phenylacetate accumulated progressively. Plasma PB concentrations (at 410 mg/kg/day) remained above the targeted therapeutic threshold of 500 micromol/liter required for in vitro activity. CONCLUSION: The DLT in this Phase I study for infusional PB given for 5 days every 21 days is neuro-cortical in nature. The recommended Phase II dose is 410 mg/kg/day for 120 h.

Adult↗
PubMed1998

A phase I/II evaluation of oral L-2-oxothiazolidine-4-carboxylic acid in asymptomatic patients infected with human immunodeficiency virus.

A randomized double-blind, placebo-controlled study was conducted in 37 asymptomatic HIV-infected individuals (mean CD4 count 707 cells/mm3) to characterize the safety, pharmacokinetics, and effect on blood thiols of three dosage levels of a cysteine prodrug, L-2-oxothiazolidine-4-carboxylic acid (OTC; Procysteine; Clintec Technologies, Deerfield, IL). Single-dose administration of OTC resulted in measurable plasma levels at all dosages, with a mean peak plasma concentration of 734 +/- 234 nmol/mL at the highest dosage studied. After 4 weeks of administration three times daily, a statistically significant increase was seen in whole blood glutathione in the 1,500 mg and 3,000 mg dose groups compared with the placebo group. A significant increase in whole blood cysteine and peripheral blood mononuclear cell (PBMC) glutathione was not seen during the study period.

Adult↗
PubMed1998

Sequence-dependent hematological toxicity associated with the 3-hour paclitaxel/cyclophosphamide doublet.

Paclitaxel is active in metastatic breast cancer. Combination studies have demonstrated complex interactions between paclitaxel and other cytotoxic agents, including sequence-dependent cytotoxic, toxicological, and pharmacological effects. The principal objectives of this study were to determine the maximum tolerated doses of paclitaxel (3-h infusion) and cyclophosphamide (1-h infusion) administered every 3 weeks with granulocyte colony-stimulating factor (Filgrastim) and to determine if the sequence-dependent toxicological effects that have previously been observed with this combination when paclitaxel was administered over 24 h were evident when paclitaxel was administered over 3 h. Fifteen women with metastatic breast cancer were treated. Starting doses were 200 mg/m2 paclitaxel and 1600 mg/m2 cyclophosphamide, with granulocyte colony-stimulating factor (5 micrograms/kg/day) given s.c. beginning 24 h after chemotherapy. Doses of both drugs were escalated in cohorts of at least four patients. The sequence of drug administration was alternated with each consecutive patient and with each subsequent course of therapy in each individual patient, enabling the evaluation of sequence-dependent toxicological and pharmacological effects. Severe myelosuppression was the principal dose-limiting toxicity for this regimen, precluding dose escalation above 200 mg/m2 paclitaxel and 1600 mg/m2 cyclophosphamide, the maximum tolerated dose for this combination on this schedule. As has been previously demonstrated with this combination, when paclitaxel is administered over 24 h, the hematopoietic toxicity was sequence dependent. Paired analysis of toxicity data using each patient as her own control indicated more severe hematological toxicity in courses in which paclitaxel was administered first. There was no evidence of sequence-dependent effects on the pharmacokinetics of these drugs that might account for this phenomenon. The impact of drug sequencing on toxicity should be considered in the further development of combination therapy containing alkylating agents and paclitaxel, when the latter is administered over 3 h.

Adult↗
PubMed1987

Simulated lift testing using computerized isokinetics.

Eighty-four volunteer asymptomatic men between 18 and 40 years of age were evaluated as to their ability to lift. An innovative isokinetic device was used to measure lifting force. This device does not isolate any specific body part, yet it measures the muscular force of lifting an object whose speed of ascent is controlled. Two lifting methods (bent knee, straight leg) and two foot positions were used. The results indicate the bent-knee lift method and forward-foot position was the position of optimal force production. Force production increase was inversely proportional to age. The authors concluded that the isokinetic lift device has promising capabilities to produce repeatable data and may be advantageous in generating standards for rehabilitation and specific job criteria.

Adolescent↗