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At least 397 records · Page 22Linked to original sources
PubMed2003

Radiotherapy in conjunction with intravenous infusion of 180 mg of disodium pamidronate in management of osteolytic metastases from breast cancer: clinical evaluation, biochemical markers, quality of life, and monitoring of recalcification using assessments of gray-level histogram in plain radiographs.

PURPOSE: To evaluate the clinical improvement and radiographically monitor the effect of local radiotherapy in conjunction with disodium pamidronate (DP) on metastatic osteolytic disease. METHODS AND MATERIALS: Thirty-three patients with osteolytic metastasis from advanced breast cancer received radiotherapy with a 6-MV linear accelerator up to a dose of 30 Gy (3 Gy/fraction, 5 d/wk) combined with 24 monthly sessions of a 180-mg DP infusion. Conventional X-rays were obtained during the first six sessions of DP treatment, retaining the same settings for each exposure. The analysis of the image attributes was based on measuring the first-order statistics of the mean value and energy of gray-level histograms in the osteolytic region. RESULTS: The 6-month measurements compared with baseline showed statistically significant differences (p < 0.01, Wilcoxon test) in energy of gray-level histogram (-10.8%), mean value of gray-level histogram (+9.5%), pain score (-5.8 points), Eastern Cooperative Oncology Group status (-2.4 points), urine hydroxyproline/creatinine ratio (-41.7%), urine calcium/creatinine ratio (-58.8%), and bone alkaline phosphatase (-42.4%). Quality of life as determined by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (version 3) also improved. During follow-up, 88% of patients had complete and 12% partial responses (International Union Against Cancer radiologic criteria). On multivariate analysis, greater changes in the mean value of the gray-level histogram and negative nodal status were predictors for a reduction in the number of skeletal complications after therapy. Flu-like syndrome occurred in 13 patients (39%) and was well managed with mild antipyretics. CONCLUSION: Image-processing in plain radiographs offers an objective way to assess recalcification. The image-processing indexes, along with the measurements of performance status, quality of life, and biochemical markers, improved significantly. Local radiotherapy combined with long-term high-dose DP up to 180 mg is tolerable and has a high therapeutic response.

Adult↗
PubMed2003

Spurious values of serum electrolytes due to admixture of intravenous infusion fluids.

Blood samples may be collected subsequent to the establishment of a working i.v. line. When collected incorrectly, such blood samples can yield spurious results of serum electrolyte and chemistry determinations. We present such a case and, further, show that serum chemistry values can be altered by contamination with i.v. fluids in the emergency patient and that such alterations can be of sufficient magnitude to affect treatment. Recommendations are given regarding aspiration of blood samples from working i.v. lines to minimize the risk of spurious measurements.

Acid-Base Equilibrium↗
PubMed1992

[Pharmacokinetics of methohexital given by constant rate intravenous infusion].

The pharmacokinetic characteristics of a constant rate methohexitone infusion were studied in young ASA 1 patients undergoing maxillofacial surgery. They were randomly assigned to two groups; group M patients (n = 7) were given 9 mg.kg-1.h-1 of methohexitone for one hour, and group MF patients (n = 7) 9 mg.kg-1.h-1 of methohexitone with 7 micrograms.kg-1.h-1 of fentanyl, also for one hour. Blood samples for determining methohexitone concentrations were obtained at various times, from before the start of the methohexitone infusion up to 19 h afterwards. In twelve patients, a two-compartment model was appropriate to characterize the decrease of methohexitone concentration; for the other two (one in each group), a three-compartment model was applied. There were no statistically significant differences between the two groups. Elimination half-life in group M was 3.22 +/- 1.96 h, and total plasma clearance 8.54 +/- 2.8 ml.kg-1.min-1. The wide variations in pharmacokinetic parameters between subjects may explain some unpredictable variations in duration of action of methohexitone. Fentanyl did not modify methohexitone pharmacokinetics, which remained of the first order. However, it potentiated the barbiturate's action: extubation was only possible after stopping the infusion for 39.4 min +/- 22 min in group MF, and 15.4 min +/- 6 min in group M (p less than 0.01). At that time, plasma concentrations were respectively 3.12 +/- 0.99 mg.l-1 (group MF) and 5.71 +/- 2.09 mg.l-1 (group M), (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1999

Safety of rapid intravenous infusion of valproate loading doses in epilepsy patients.

IV valproate may be given to patients requiring rapid elevation of serum valproate or for patients unable to take oral medication. Previously we established the loading dose of IV valproate needed to achieve serum concentrations of > 100 ug/ml. This study evaluated the safety of rapid infusion of valproate to achieve high therapeutic levels. Twenty-four infusions of IV valproate were carried out electively in twenty-one patients with epilepsy (ages 2-54 years). The dose ranged from 21-28 mg/kg (mean 24.2 mg/kg). Target infusion rates were 3 or 6 mg/kg per min, yielding an infusion duration of 4.17 or 8.34 min. ECG was monitored; blood pressure was measured before and after infusion. Post infusion serum valproate concentrations were 64-204.1 ug/ml (mean 132.6). There were no significant changes in blood pressure and no ECG abnormalities observed. Transient pain occurred at the site of injection in five patients, associated with redness in two. This appeared to related to the concentration of valproic acid in the infusion fluid. We conclude that a loading dose of IV valproate can be administered safely and rapidly. This finding enables further studies evaluating IV valproate as a non-sedative anticonvulsant in the management of status epilepticus.

Adolescent↗
PubMed1996

Modeling solute sorption into plastic tubing during organ perfusion and intravenous infusions.

The uptake of solutes into plastic infusion and perfusion tubing has been well documented, but the kinetics of the uptake process is not well-defined. Three mathematical models have been developed to describe the outflow fraction concentration--time profiles for solutes sorbed into the plastic tubing during infusion and perfusions. The models are referred to as model 1, convection--diffusion; model 2, convention-- interfacial resistance--diffusion; ad model 3, convection--interfacial resistance--infinite sink models. In each model, plug flow is assumed and, in order to minimize the number of variables required, solutions are limited to early times when the plastic behaves as an infinite sink. Initial conditions of (i) no solution in the tubing and (ii) a preloading of tubing with drug solution are considered for each of the three models. Two parameters, one being the transit time of solution through tubing (tmin) and the other a measure of the affinity and diffusivity of the solute in the plastic (SN), are sufficient to describe the outflow concentration--time profiles for solutes with sorption into tubing being limited by diffusion in the plastic (model 1). A single parameter, which is the effective interfacial permeability coefficient (H), is sufficient to describe the outflow concentration--time profiles for solutes with sorption into tubing being limited by an aqueous--plastic interfacial barrier (model 3). The three parameters (tmin, SN, and H) are required when uptake into tubing is limited by a combination of diffusion into plastic and an interfacial resistance (model 3). Each model has a characteristic outflow concentration--time profile determined by the relative magnitude of diffusivity of the solute in the plastic to that across the interfacial barrier. The sorption of nitroglycerin and isosorbide dinitrate are adequately described by the convection--diffusion model (model 1 (ii)) whereas the convection--interfacial resistance--diffusion model (model 2 (ii)) is required to describe the sorption of diazepam and chlorpromazine.

Adsorption↗
PubMed1997

Effects of intravenous infusion of lidocaine on its pharmacokinetics in conscious instrumented dogs.

In this study, potential alterations in hepatic blood flow, plasma protein binding, hepatic tissue binding, and enzyme activities induced by LD iv infusion of lidocaine (LD) were evaluated using a chronically instrumented dog model. Four conscious female mongrel dogs (19.0-23.5 kg) were each given, on days 1 and 10, a 5-min infusion of a mixture of unlabeled LD at approximately 2 mg/kg and 14C-labeled LD at approximately 25 microCi and, on day 8, a 12-h constant rate iv infusion of LD (approximately 76 microg/kg/min). During LD infusion, there was a 11-79% increase in total hepatic blood flow, mainly due to a 1.6-9.2-fold increase in hepatic arterial flow. Despite similar blood clearance (27.5 +/- 6.0 mL/min/kg vs 27.5 +/- 3.5 mL/min/kg), volume of distribution at steady state (1.38 +/- 0.08 L/kg vs 1.36 +/- 0.17 L/kg), and free fraction values of LD between days 1 and 10 (p > 0.05), intrinsic clearance values were consistently reduced (1224 +/- 859 mL/ min/kg vs 285 +/- 104 mL/min/kg; p = 0.034). Furthermore, hepatic tissue uptake of LD and/or its metabolites was less on day 10 than on day 1 (39.7 +/- 14.5 micromol vs 30.1 +/- 15.1 micromol; p = 0.072). The extent of N-dealkylation of LD to MEGX was unaltered, whereas sequential biotransformation of MEGX was impaired. Hence, these findings suggested that LD infusion led to a reduction of hepatic intrinsic clearance, although the change was not significant enough to alter its conventional kinetic parameters.

Animals↗
PubMed2001

In vivo cerebral pharmacokinetics and pharmacodynamics of diazepam and midazolam after short intravenous infusion administration in sheep.

The cerebral pharmacokinetics and pharmacodynamics of midazolam and diazepam were examined in chronically instrumented sheep via measurements of their arterio-venous concentration difference across the brain during and after 2-min i.v. infusions. Diazepam (30 mg) or midazolam (10 mg) were administered on 5 separate occasions to 4 sheep. For both drugs, rapid cerebral uptake occurred during the infusion, which quickly turned to elution in the postinfusion period. However, this process was more rapid for midazolam than diazepam. The cerebral pharmacokinetics of both was better described by a kinetic model with slight membrane limitation rather than flow limitation. For diazepam, the estimated brain:plasma partition coefficient was 2.67, and the first and second compartments filled with half-lives of 2.2 and 0.5 min, respectively. For midazolam, these values were 0.27, 0.26 and 1.34 min, respectively. In a subset of sheep, pulmonary arterial-arterial gradients were too small to measure suggesting limited metabolism and small distribution volumes for both drugs in the lungs. Simultaneous dynamic measurements of cerebral blood flow and algesimetry lagged behind both the arterial and sagittal sinus blood concentrations. The changes in cerebral blood flow were best described by a previously published a dynamic model that incorporated long half-lives for drug dissociation from the benzodiazepine receptor (13.3 and 5.5 min for midazolam and diazepam, respectively). Effect compartment modeling of the cerebral blood flow data showed apparent effect compartment half-lives (t1/2,keo) that were longer than the half-lives of cerebral equilibration.

Animals↗
PubMed1999

Pharmacokinetics of methotrexate in the extracellular fluid of brain C6-glioma after intravenous infusion in rats.

PURPOSE: Establishment of the pharmacokinetic profile of methotrexate (MTX) in the extracellular fluid (ECF) of a brain C6-glioma in rats. METHODS: Serial collection of plasma samples and ECF dialysates after i.v. infusion of MTX (50 or 100 mg/kg) for 4 h. HPLC assay. RESULTS: Histological studies revealed the presence of inflammation, edema, necrosis, and hemorrhage in most animals. In vivo recovery (reverse dialysis) was 10.8 +/- 5.3%. MTX concentrations in tumor ECF represented about 1-2% of the plasma concentrations. Rapid equilibration between MTX levels in brain tumor ECF and plasma. ECF concentrations almost reached steady-state by the end of the infusion (4 h), then decayed in parallel with those in plasma. Doubling of the dose did not modify MTX pharmacokinetic parameters (t1/2alpha, t1/2beta, MRT, fb, Vd, and CL(T)), except for a 1.7-fold increase of AUC(Plasma) and a 3.8-fold increase in AUC(ECF), which resulted in a 2.3-fold increase in penetration (AUC(ECF)/AUC(Plasma)). In spite of an important interindividual variability, a relationship between MTX concentrations in plasma and tumor ECF could be established from mean pharmacokinetic parameters. CONCLUSIONS: High plasma concentrations promote the penetration of MTX into brain tissue. However, free MTX concentrations in tumor ECF remain difficult to predict consistently.

Animals↗
PubMed1978

Effect of self-determined intravenous infusion of hypertonic NaCl on Na appetite of sheep.

The time delay that occurs between a rapid, systemically produced change in Na balance and a change of voluntary Na intake was examined in Na-deficient sheep with a parotid fistula. They were trained to bar press in order to replace a daily Na deficit of 300--500 mmol. During basal conditions on different days, each delivery to a drinking cup consisted of either a small or a large amount of NaHCO3 solution. In the experimental situation, the small amount of NaHCO3 was delivered to the cup, but total Na delivered was made to equal that of the large amount by automatic concurrent infusion of hypertonic NaCl intravenously with each delivery to the cup. As a control, the concurrent intravenous infusion was .15 M NaCl, which had little influence on Na balance. A significant difference in the cumulative number of deliveries between the hypertonic and isotonic NaCl infusion conditions occurred by 10--20 min. It is concluded that systemic injections of hypertonic NaCl are effective within 10 to 20 min in reducing the sodium appetite of Na-depleted animals.

Animals↗
PubMed2006

A phase II study of Yondelis (trabectedin, ET-743) as a 24-h continuous intravenous infusion in pretreated advanced breast cancer.

Yondelis (trabectedin, ET-743) is a novel marine-derived anticancer compound found in the ascidian Ecteinascidia turbinata. It is currently under phase II/III development in breast cancer, hormone refractory prostate cancer, sarcomas and ovarian cancer. Activity in breast cancer experimental models has been reported, and preliminary evidence of activity in this setting during the phase I programme has also been observed. The present study assessed the activity and feasibility of trabectedin in women with advanced breast cancer previously treated with conventional therapies. Patients with advanced disease previously treated with at least one but not more than two regimens that included taxanes or anthracyclines as palliative therapy were eligible. Trabectedin 1.5 mg m(-2) was administered as a 24-h continuous infusion every 3 weeks. Patients were kept on therapy until disease progression, unacceptable toxicity or patient refusal. Twenty-seven patients were included between April 1999 and September 2000. Their median age was 54 years (range: 36-67) and 63% of them had two metastatic sites. Twenty-two patients were performance status 1. All patients had previously received anthracyclines, and 23 out of 27 patients had received taxanes. Of 21 patients with measurable disease, three confirmed partial responses, one unconfirmed partial response and two minor responses (49 and 32% tumour shrinkage) were observed; six patients had stable disease. Median survival was 10 months (95% confidence interval: 4.88-15.18). Transient and noncumulative transaminitis was observed in most of the patients. The pharmacokinetic profile of trabectedin in this patient's population is in line with the overall data available with this schedule. The policy of dose adjustments based on the intercycle peaks of bilirubin and alkaline phosphatase appears to have a positive impact in the therapeutic index of trabectedin. Trabectedin can induce response and tumour control in previously treated advanced breast cancer, with manageable toxicity, thus warranting further development as a single agent or in combination regimens.

Adult↗