Biomedical subjects

A Aldaz

Publications and source records attributed to A Aldaz.

11 recordsLinked to original sources

PubMed2001

Separation methods for camptothecin and related compounds.

This paper reviews working procedures for the analytical determination of camptothecin and analogues. We give an overview of aspects such as the chemistry, structure-activity relationships, stability and mechanism of action of these antitumor compounds. The main body of the review describes separation techniques. Sample treatment and factors influencing high-performance liquid chromatography development are delineated. Published high-performance liquid chromatographic methods are summarized to demonstrate the variability and versatility of separation techniques and a critical evaluation of separation efficiency, detection sensitivity and specificity of these methods is reported.

Antineoplastic Agents, Phytogenic↗

PubMed2001

Simple and rapid determination of carboplatin in plasma by high-performance liquid chromatography. Error pattern and application to clinical pharmacokinetic studies.

Carboplatin is an antitumor agent widely employed in cancer chemotherapy. A specific and selective method for the determination of carboplatin in human plasma and its applications to pharmacokinetic investigations is described. One ultrafiltration step, through a Centrifree micropartition system (Amicon) at 2000 g for 10 min, is the only requirement as sample treatment. The resulting solution is injected into an Inertsil ODS-2 (5 microm, 25 cm x 4.6 mm I.D.) analytical column. The mobile phase consisted of 0.1 M potassium dihydrogenphosphate with 1 mM dipotassium edetate adjusted to a pH between 3 and 3.5. The limit of quantitation was 1 mg/l. The method showed good recovery (100.68+/-5.49%) and precision: the within-day relative standard deviation (RSD) for carboplatin (3-350 mg/l) was 2.07% and the between-day RSD for carboplatin, in the previously described range, was 1.31%. We determined the assay error pattern for proper weighting of serum level data in pharmacokinetic models. The selectivity (discrimination between the parent drug and platinum-containing species such as carboplatin metabolites), simplicity and speed of this assay for free carboplatin quantitation should facilitate pharmacokinetic investigations and therapeutic drug monitoring.

Antineoplastic Agents↗

PubMed2001

Influence of chloride ion on electrochemical degradation of phenol in alkaline medium using bismuth doped and pure PbO2 anodes.

Electrochemical method at laboratory scale for the treatment of biorefractory solutions with high phenol content--1000 ppm is described. Total degradation of phenol was obtained at alkaline pH when NaCl was present using Bi-doped and pure lead dioxide electrodes. A filter press cell of 63 cm2 geometric area was used for this purpose. Measurements of chemical oxygen demand (COD), phenol, carbon monoxide, carbon dioxide, and volatile organic compounds (VOCs) have been used to characterise the electrochemical process for phenol elimination. It is worth noting that in the absence of NaCl, the charge efficiency of COD removal was independent of the current density in the range studied (50-100 mA cm(-2)) Moreover, when NaCl was present, the current efficiency for COD and phenol removal increase as the chloride concentration increases. Chloroform was the only halocompound detected at the end of reaction. For both electrodes, Bi-doped and pure lead dioxide, the chloroform concentration at the end of the electrolysis decreases, working at low current densities and for low chloride concentrations.

Anions↗

PubMed2000

Simple and rapid determination of irinotecan and its metabolite SN-38 in plasma by high-performance liquid-chromatography: application to clinical pharmacokinetic studies.

Irinotecan (CPT-11) is an anticancer agent widely employed in the treatment of colorectal carcinoma. A simple, rapid and sensitive high-performance liquid chromatographic method for the simultaneous determination of CPT-11 and its metabolite SN-38 in plasma, and their preliminary clinical pharmacokinetics are described. Both deproteinisation of plasma specimens (100 microl) and addition of the internal standard, camptothecin (CPT), are achieved by incorporating to samples 100 microl of a solution of CPT (1 microg/ml) in acetonitrile-1 mM orthophosphoric acid (90:10); 200 microl of this acidified acetonitrile solution, drug-free, is also added to accomplish complete deproteinisation: this procedure reduces sample preparation time to a minimum. After deproteinisation, samples are treated with potassium dihydrogenphosphate (0.1 M) and injected into a Nucleosil C18 (5 microm, 250 x 4.0 mm) column. Mobile phase consists of potassium dihydrogenphosphate (0.1 M)-acetonitrile (67:33), at a flow-rate of 1 ml/min. CPT-11, SN-38 and CPT are detected by fluorescence with excitation wavelength set at 228 nm and emission wavelengths of CPT-11, SN-38 and CPT fixed, respectively, at 450, 543 and 433 nm. The limits of quantitation for CPT-11 and SN-38 are 1.0 and 0.5 ng/ml, respectively. This method shows good precision: the within day relative standard deviation (RSD) for CPT-11 (1-10000 ng/ml) is 5.17% (range 2.15-8.27%) and for SN-38 (0.5-400 ng/ml) is 4.33% (1.32-7.78%); the between-day RSDs for CPT-11 and SN-38, in the previously described ranges, are 6.82% (5.03-10.8%) and 4.94% (2.09-9.30%), respectively. Using this assay, plasma pharmacokinetics of CPT-11, SN-38 and its glucuronidated form, SN-38G, have been determined in one patient receiving 200 mg/m2 of CPT-11 as a 90 min intravenous infusion. The peak plasma concentration of CPT-11 at the end of the infusion is 3800 ng/ml. Plasma decay is biphasic with a terminal half-life of 11.6 h. The volume of distribution at steady state (Vss) is 203 l/m2, and the total body clearance (Cl) is 14.8 l/h x m2. The maximum concentrations of SN-38 and SN-38G reach 28.9 and 151 ng/ml, respectively.

Area Under Curve↗

PubMed2000

Effects of hepatic function on vancomycin pharmacokinetics in patients with cancer.

Vancomycin is widely used in the prophylaxis and treatment of infections in neutropenic patients with cancer. The objective of this study was to analyze liver damage effects on vancomycin pharmacokinetics and determine the necessity for liver function evaluation when selecting vancomycin dosing schedules in these patients. A population pharmacokinetic analysis was performed using the global two-stage method. To this purpose serum vancomycin concentrations from 154 cancer patients were measured and individual vancomycin pharmacokinetic parameters were estimated by the Sawchuk and Zaske method. Mean and standard deviation of the vancomycin pharmacokinetic parameters were estimated for various subgroups of patients classified according to the degree of liver damage. Then a multiple linear regression analysis was performed to select the best predictive models for vancomycin clearance (Clvan) and steady state distribution volume (V). Results revealed that Clvan is not influenced by liver failure. Differences in V between patients with and without hepatic failure were initially observed, but these disappeared when patients with ascites were excluded. In conclusion, vancomycin dosing schedule does not need to be modified for patients with liver failure, with the exception of patients with ascites.

Adolescent↗

PubMed2000

Potential interaction between methotrexate and omeprazole.

OBJECTIVE: To report a case of delayed elimination of high-dose methotrexate (MTX) associated with concomitant omeprazole administration. CASE SUMMARY: Delayed MTX elimination was observed in an 11-year-old white boy who concomitantly received high-dose MTX and omeprazole. The patient's serum creatinine and liver function tests were normal during treatment and follow-up. The only medication we suspected of inhibiting MTX elimination was omeprazole 20 mg every 12 hours. Twenty-four hours after the first high-dose MTX cycle (15 g), omeprazole was discontinued. Thereafter, the patient received one high-dose MTX cycle without omeprazole every month for five months; MTX elimination was normal throughout MTX cycles 2 to 5. DISCUSSION: MTX is actively secreted in the distal tubules. The renal hydrogen/potassium adenosine triphosphatase (H+/K(+)-ATPase) pump makes the urine more acidic, by secreting hydrogen ions into the renal tubule and reabsorbing potassium ions. Active tubular secretion of MTX requires the activity of this pump because MTX is excreted with hydrogen ions. Omeprazole can inhibit renal elimination of the hydrogen ion and block the active tubular secretion of MTX. Therefore, the elimination half-life of MTX increases, which may result in potentially toxic concentrations of MTX. At a pH of approximately 5, as found in the renal tubules, pantoprazole is more slowly activated than omeprazole, reducing the incidence of unwanted reactions with sulfhydryl groups and adverse effects occurring outside of the gastric hydrogen pump. CONCLUSIONS: Based on the Naranjo probability scale, a probable drug interaction was observed. Omeprazole may delay MTX elimination; therefore, when prescribing MTX, an alternative to omeprazole should be considered.

Child↗

PubMed1999

Simple and sensitive determination of 5-fluorouracil in plasma by high-performance liquid chromatography. Application to clinical pharmacokinetic studies.

5-Fluorouracil (5-FU) is an antineoplastic agent widely employed in the treatment of many types of cancer. Recent studies have proved the need for individual adjustment of 5-FU dosage based on pharmacokinetics. A simple and sensitive high-performance liquid chromatographic method for the determination of 5-FU in plasma and their preliminary clinical pharmacokinetics is described. After sample acidification with 20 microl of orthophosphoric acid (5%), the drug is extracted from plasma using n-propanol-diethyl ether (16:84). The organic layer is evaporated to dryness, the residue dissolved in 100 microl of mobile phase and 20 microl of this mixture is injected into a LiChrospher 100RP-18 (5 microm, 250 x 4.0 mm) analytical column. Mobile phase consisted of potassium dihydrogenphosphate (0.05 M, adjusted to pH 3). The limit of quantitation was 2 ng/ml. The method showed good precision: the within-day relative standard deviation (RSD) for 5-FU (10-20,000 ng/ml) was 3.75% (2.57-5.93); the between-day RSD for 5-FU, in the previously described range, was 5.74% (4.35-7.20). The method presented here is accurate, precise and sensitive and it has been successfully applied for 5-FU pharmacokinetic investigation and therapeutic drug monitoring.

Chemical Precipitation↗

PubMed1999

Use of thiobacillus ferrooxidans in a coupled microbiological-electrochemical system for wastewater detoxification

We have developed a mixed system, electrochemical-microbiological, that can be used for detoxifying organic compounds present in wastewater. In this system, organic matter oxidation takes place at the anode of an electrochemical reactor while ferric iron reduction takes place at the cathode. We have used a growing culture of Thiobacillus ferrooxidans to regenerate the ferric ions consumed. The culture is used as the catholyte (solution in the cathode compartment) of the system and is therefore permanently subjected to an electric field. We have verified that, under our working conditions, the culture is able to oxidize ferrous ions for long periods of time (up to 15 days) depending on the intensity of the applied current. We have checked the performance of this system in methanol oxidation. Our results show that it decreases the energy cost by 35% when com- pared with the pure electrochemical system traditionally used. Copyright 1999 John Wiley & Sons, Inc.

Journal Article↗

PubMed1999

Relationship between pharmacokinetic parameters of gentamicin and patient characteristics and/or clinical data in patients with solid organ tumours.

Gentamicin monitoring and the selection of the initial dosage are generally based on the relationship between pharmacokinetic parameters of gentamicin (GPP) and patient characteristics and/or clinical data (PC). However, the number of studies about this relationship in cancer patients is limited. Therefore, the main objective of the present study was to evaluate the relationship between GPP and PC in cancer patients and to identify different subgroups within this group of patients with unique relationship models between GPP and PC. A total of 198 cancer patients were included in the study. Firstly, GPP were estimated by the Sawchuk and Zaske regression method. Then, a linear regression analysis was performed to investigate the relationship between GPP and PC, and lastly subgroups with unique models were identified by comparing their regression models. The results revealed that the variable which was the best predictor of the distribution volume of gentamicine was the dosing weight (DW = IBW + (ABW-IBW), ABW being the actual body weight and IBW the ideal body weight). Creatinine clearance (CLCR) measured by a 24-hour urine collection (CLCRu) was the best predictor of gentamicin clearance (CL). When this value is not available, the CLCR estimated by the formula of Crockcroft and Gault (C-G), can be used. When the C-G formula was used, unique models to predict CL from CLCR were identified for patients who were obese, patients who had received high-dose chemotherapy and, for subjects who had never developed aplasia following chemotherapy. Whichever the model used, the results showed that some variability in pharmacokinetic parameters of gentamicin was not explained by the models, especially in some groups of patients.

Creatinine↗

PubMed1998

Population pharmacokinetic parameters of gentamicin in patients with solid tumors: estimation by one- and two-stage methods.

Gentamicin monitoring has been improved with the introduction of Bayesian methods but the usefulness depends on the quality of the population parameters (PP) used. The objective of this study was to determine PP of gentamicin in patients with solid tumors. A total of 198 adult patients with cancer were included in the analysis. Population parameters were estimated by both a two-stage and a one-stage method (NPEM, Non Parametric Expectation Maximization). Individual parameters (IP) were estimated by the Sawchuk-Zaske method and by nonlinear regression. The estimated distribution volume and clearance of gentamicin (mean +/- SD) were 18.37 +/- 5.021 (0.30-0.32 l/kg of dosing weight) and 3.34 +/- 1.6 l/h, respectively. No significant differences between IP or PP obtained by the different methods were found. The results indicated a wide variability of gentamicin pharmacokinetics making monitoring necessary and that patients with solid tumors may have larger gentamicin volume and slower clearance than normal patients. These observations imply that different population pharmacokinetic parameters should be used for this group of patients.

Adult↗

PubMed1995

Cost-evaluation model for clinical trials in a hospital pharmacy service.

A cost-evaluation model was applied to clinical trial protocols to estimate their cost for the hospital pharmacy service. The steps taken in the drug management of clinical research were identified. Fixed costs (common to all clinical trials) and variable costs (peculiar to each clinical trial) were determined for each step. The number of patients, the number of operations, the planned services (receptions, storage, drug dispensing), the timing and difficulty of the study (randomization) were included in the variable costs. The economic assessment of these items was based on the costs of the materials and means used, the cost of staff time and finally the cost of drug storage during the clinical trial. This model was applied to 24 clinical trials carried out in the University Clinic of Navarra. 83% of all pharmacy costs of a clinical trial were variable. Drug dispensing, stock management and return drugs account for 94% of the time expended. The approximate cost of the pharmacy providing investigational services was $1,766 per trial or $174 per patient. Drug storage costs were not an important source of expenditure among the variable costs (7.4%). The best way to determine the cost of a trial is to calculate the number of operations.

Clinical Trials as Topic↗