Effects of sunflower soap stocks on light lamb meat quality.

Thirty-two lambs were used to study the effect of sunflower soap stocks (SS), a by-product from the vegetable oil refinery industry, on meat chemical composition, fatty acid profile, volatile compounds, and consumer acceptability. Lambs were finished (average length of fattening period 35 ± 7.3 d, 26.8 ± 0.09 kg final BW) on a pelleted total mixed ration (TMR) with no SS (00SS) or including 15, 30 or 60 g SS/kg (15SS, 30SS, and 60SS, respectively). Sunflower soap stocks decreased the percentage of SFA, increased the proportion of -MUFA ( < 0.05), and modified the levels of several odor-active lipid-derived volatile compounds ( 0.05). Consumers were able to distinguish between control and 15SS meat samples in a triangular test ( < 0.05), but a well-defined preference for meat of any of these treatments was not exhibited ( > 0.05). Atherogenicity and saturation indexes decreased by 31% and 27%, respectively, in SS groups compared to control (linear 0.05). However, certain volatile compounds (benzene and toluene) and 10-18:1 fatty acid, known potential hazards for human health, were increased in meat from lambs fed TMR with SS. For this reason, only inclusion rates up to 15 g SS/kg TMR seem to sustain a satisfactory balance between beneficial and detrimental effects on lamb meat composition and quality.

The value of genetic polymorphisms to predict toxicity in metastatic colorectal patients with irinotecan-based regimens.

PURPOSE: We are trying to identify predictive factors of high risk of toxicity by analyzing candidate genes in the irinotecan pathways in order to identify useful tools to improve mCRC patient management under real practice conditions. METHODS: Genomic DNA was genotyped for UGT1A1 (*28, *60 and *93) from all 101 patients, and irinotecan dose was 180 mg/m(2) every second week. Clinical data were obtained by retrospective chart review. The primary endpoint is to find out whether the pharmacogenetic test in the clinical practice may predict toxicity. RESULTS: Grade 3/4 diarrhea occurred in twelve patients and required dose reduction in six patients, and neutropenia reached grade 3/4 in 19 patients (only one patient with *28/*28 genotype). The UGT1A1*93 seemed to relate with grade 3/4 neutropenia but only in the heterozygote state (G/A), p = 0.071, and UGT1A*60 showed no association with neutropenia. Twenty-eight percentage of patients required the use of G-CSF; 64.3% of them harbored *1/*28 or *28/*28 genotypes, p = 0.003. Thirty-seven (36.6%) patients required dose reduction of irinotecan and/or 5-FU owing to toxicity, mainly neutropenia and diarrhea. No significant association was detected between *28, *60 and *93 UGT1A variants and severe irinotecan-associated hematologic or GI toxicity. CONCLUSION: The impact of increased risk of toxicity attributed to the UGT1A variants may be offset by irinotecan in clinical practice by dose reduction or the use of colony-stimulating factor.

Description of the seasonal pattern in ozone concentration time series by using the strange attractor multifractal formalism.

Ozone is a secondary pollutant that, at high concentrations in urban environment, affects human health. Thus, suitable knowledge of ozone dynamics is essential for avoiding undesirable effects on the population. Ten-minute ozone concentration time series recorded at Córdoba (southern Spain) in 2007, for January, April, July and October, have been analysed by using the strange attractor multifractal formalism with the aim of describing the seasonal pattern of this pollutant. The multifractal nature of ozone concentration was detected in a study of the mass exponent functions for autumn-winter and spring-summer seasons. Multifractal spectra showed a greater heterogeneity in the low values of the time series. The presence of rare values in ozone data sets was also investigated, showing that the multifractal approach provided considerable detailed information on the time series structure that completes the statistical descriptive analysis.

Endemic linezolid-resistant Staphylococcus epidermidis in a critical care unit.

The aim of this article was to report the emergence of patient infections with linezolid-resistant Staphylococcus epidermidis (LRSE) in a tertiary university hospital. Our objectives were to determine the molecular mechanism of the resistance, set up the genetic relationship among isolates, and analyze the relations between linezolid usage, period of treatment, and emergence of resistance in the hospital. The emergence of infection with linezolid-resistant S. epidermidis affecting 20 patients in a tertiary university hospital was investigated using repetitive sequence-based PCR (rep-PCR, DiversiLab System; BioMérieux, Inc., France). The presence of the G2576T mutation of 23S rRNA was screened by pyrosequencing. We determined the pattern of linezolid usage in the hospital as a whole and in the critical care unit that was most affected. G2576T mutation of 23S rRNA was detected in all linezolid-resistant S. epidermidis studied. Of these, 90% were genetically related and had been recovered from patients admitted to the same critical care unit. There had been an increase in linezolid usage in the hospital and in the critical care unit in the 2 years prior to the emergence of resistant strains. More strict control measures in hand washing and linezolid prescription were subsequently established, but no reduction in LRSE rates have yet been observed. Linezolid-resistant S. epidermidis emerged at our hospital, probably from a single strain originating in the critical care unit. The most likely explanation is that person-to-person spread of linezolid-resistant S. epidermidis led to skin colonization and, after linezolid treatment, this resistant staphylococci became the dominant cutaneous flora causing infection in some critical patients. In order to preserve the usefulness of this antibiotic as a therapeutic agent and to avoid a situation similar to methicillin-resistant Staphylococcus aureus, judicious use of antibiotics is essential.

The impact of agricultural soil erosion on the global carbon cycle.

Agricultural soil erosion is thought to perturb the global carbon cycle, but estimates of its effect range from a source of 1 petagram per year(-1) to a sink of the same magnitude. By using caesium-137 and carbon inventory measurements from a large-scale survey, we found consistent evidence for an erosion-induced sink of atmospheric carbon equivalent to approximately 26% of the carbon transported by erosion. Based on this relationship, we estimated a global carbon sink of 0.12 (range 0.06 to 0.27) petagrams of carbon per year(-1) resulting from erosion in the world's agricultural landscapes. Our analysis directly challenges the view that agricultural erosion represents an important source or sink for atmospheric CO2.

Image-guided surgical microscope with mounted minitracker.

A new image-guided microscope using augmented reality overlays has been developed. Unlike other systems, the novelty of our design consists in mounting a precise mini and low-cost tracker directly on the microscope to track the motion of the surgical tools and the patient. Correctly scaled cut-views of the pre-operative computed tomography (CT) stack can be displayed on the overlay, orthogonal to the optical view or even including the direction of a clinical tool. Moreover, the system can manage three-dimensional models for tumours or bone structures and allows interaction with them using virtual tools, showing trajectories and distances. The mean error of the overlay was 0.7 mm. Clinical accuracy has shown results of 1.1-1.8 mm.

Tegafur and 5-fluorouracil pelvic tissue concentrations in rectal cancer patients receiving preoperative chemoradiation.

BACKGROUND AND PURPOSE: To investigate the presence of 5-Fluorouracil (5-FU) in pelvic tissue after oral administration of tegafur. To measure tegafur and 5-FU concentrations in normal rectal mucosa, perirectal fat and residual tumor in rectal cancer patients receiving preoperative chemoradiation. To correlate drug concentrations with cancer downstaging effects. PATIENTS AND METHODS: Three tissue samples taken from 16 surgical specimens after recto-sigmoid resection were analyzed. Tegafur and 5-FU concentrations were measured using high-performance liquid chromatography. 16 patients with locally advanced rectal cancer were treated with preoperative pelvic irradiation (45-50 Gy) sensitized with oral tegafur (400 mg for every 8 hours daily). Seven patients received a precharge dose of tegafur (400 mg oral every 8 hours) 24 hours before surgery. RESULTS: In 8 of the 9 patients who did not receive a precharge dose, detectable levels of tegafur were observed in fat tissue, normal mucosa and tumor, but detectable 5-FU levels were only observed in one patient. Mean concentrations (ranges) for tegafur in fat, normal mucosa and tumor in patients without the precharge dose were 72.19 (12.1-205.6), 179.53 (11.30-727.7) and 252.35 (27.9-874.6) ng/g, respectively; mean concentrations for 5-FU in the same samples were 0.95, 1.92 and 2.68 ng/g (1 patient), respectively. In patients receiving a tegafur precharge, both tegafur and 5-FU were present in all tissue samples with the exception of 2 fat samples, in which drug concentrations were undetectable. 5-FU levels were higher in tumor than other sites, with a median value of 68.24 ng/g (range 3.8-283.05 ng/g). Tegafur levels were also higher in tumor samples than other sites (mean 3446.53 ng/g, range 1044.5-7847.0 ng/g), except in 2 patients who had higher levels of tegafur in normal mucosa. CONCLUSIONS: Tegafur and 5-FU are not always present in pelvic tissues 5 to 6 weeks after oral administration of tegafur. Both drugs were present in the tissues analyzed, in relevant concentrations, 24 hours after oral administration of tegafur. The data obtained suggest a tendency (not significant) toward a correlation between levels of 5-FU present in the residual tumor and cancer downstaging.

[Prostatic stromal sarcoma in a 20-year-old patient]. / Sarcoma del estroma prostático en un paciente de 20 años de edad.

OBJECTIVE: Prostatic tumors are the most frequent malignant neoplasms in men, most of them being constituted by carcinomas; only 0.2% of malignant prostatic neoplasms are of mesenchimal origin. They are not well known, especially those of prostatic stromal phenotype. METHODS AND RESULTS: We report the case of a 20 year-old man with a prostatic stromal sarcoma. After total cystoprostatectomy a tumor measuring 8 cm could be seen, replacing almost the whole prostate. Microscopically a spindle cell neoplasia with moderate atypia and a high mitotic index entrapping few elongated prostatic ducts (adopting a phyllodes tumor morphology) was observed. CONCLUSION: The clinical behavior of these infrequent sarcomas is not well-established. Recurrences are not uncommon whereas lung and bone metastases have been described. Twelve months after surgery our patient is alive without evidence of disease.

Simple determination of capecitabine and its metabolites by liquid chromatography with ultraviolet detection in a single injection.

Capecitabine (N4-pentoxycarbonyl-5'-deoxy-5-fluorocytidine, Xeloda), a prodrug of 5-fluorouracil (5-FU), is an oral tumor-selective fluoropyrimidine carbamate approved in the treatment of colorectal and breast cancer. It has a preferential activation to 5-FU by thymidine phosphorilase (TP) in target tumor tissues through a series of three metabolic steps minimizing the exposure of normal tissues to 5-FU. It offers the potential of less gastrointestinal toxicity and advantages in terms of convenience and quality of life for the patient, in addition to cost-effectiveness as compared with intravenous 5-FU chemotherapy. We developed a high performance liquid chromatography assay for the determination of plasma capecitabine and its nucleoside metabolite concentrations and 5-FU catabolite dihydro-5-fluorouracil in a single step extraction and a single HPLC injection. The retention times of dihydro-5-fluorouracil, 5-FU, 5'-deoxy-5-fluorouridine (5'-DFUR) and capecitabine were 3.6, 4.4, 11.4 and 20.4 min, respectively and the internal standard retention times were 8.7 and 12.2 min for 5-bromouracil (5-BU) and tegafur, respectively. The limit of detection was 0.01 microg/ml for capecitabine and its nucleoside metabolites and the limit of quantification was 0.025 microg/ml. Extraction efficiency was >80% with a single solvent mixture extraction step for all analytes of interest. The assay had good precision, the within-day and between-day standard deviation of the mean (R.S.D.) being <10% in the linear range 0.025-10 microg/ml. The authors conclude that the method described here is ideally suited for the therapeutic monitoring of capecitabine and its metabolites.

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.

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.

Cost analysis of neuromuscular blocking agents in the operating room: cisatracurium, atracurium, vecuronium and rocuronium.

Cisatracurium (C), Atracurium (A), Rocuronium (R) and Vecuronium (V) are four neuromuscular blockers (NMB) used in the operating room with similar efficacy, defined as adequate muscle relaxation, but different pharmacokinetics. C and A have organ-independent elimination, A is associated with histamine release and R has a shorter onset time. The objective of this study was to economically compare these four NMB from the hospital point of view in order to facilitate drug selection. A cost analysis was performed. Only direct costs were considered and data were collected through a retrospective chart review. A total of 151 patient charts were randomly selected. Differences between patients receiving one of the four NMB were evaluated by ANOVA or Kruskal-Wallis tests. Then a multiple linear regression analysis was conducted. In the chart review, no significant difference was observed between the four groups of patients in age, weight or surgery duration (p > 0.05). Multiple regression analysis revealed that atracurium was on average PTA 237 (1 Euro = PTA 166) cheaper per surgery than any other NMB after adjusting for other factors (p < 0.01) and there is no significant difference in cost between the other three NMBs (p > 0.1). We recommend the use of rocuronium when a quick onset is needed and the patient does not have hepatic failure, cisatracurium when a haemodynamic instability is possible and atracurium in the remaining cases. If just one NMB can be included in the drug formulary we would select cisatracurium due to its pharmacological advantages over atracurium with a small increment in cost.

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.

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.

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.

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.

Expression of basic fibroblast growth factor and its receptors FGFR1 and FGFR2 in human benign prostatic hyperplasia treated with finasteride.

BACKGROUND: The development of benign prostatic hyperplasia (BPH) is an androgen-dependent process which may be mediated by a number of locally produced growth factors. One of these, the basic fibroblast growth factor (bFGF or FGF2), has a mitogenic effect on prostatic stroma. High expression levels of bFGF have been reported in BPH. FGFR1 and FGFR2 receptors, that exhibit affinity for bFGF, have been identified in normal and hyperplastic prostate. Finasteride, a 5alpha-reductase inhibitor, is an effective drug in the treatment of BPH, inducing regressive changes in the prostate of treated patients, even though its mechanisms of action are not yet completely elucidated. This study was designed to assess the effects of finasteride on the expression levels of bFGF, FGFR1, and FGFR2 in patients with BPH. METHODS: The expression levels of bFGF, FGFR1, and FGFR2 in 9 patients with prostatic hyperplasia treated with finasteride were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis of mRNA expression and were compared with those of 9 control patients with untreated BPH. RESULTS: Immunohistochemistry showed strong bFGF immunoreactivity in the prostatic stroma of untreated patients, this being somewhat weaker in the epithelium. In treated patients, epithelial immunoreactivity was practically negative, and a considerable reduction in stromal immunoreactivity was seen. These findings were also confirmed by RT-PCR. FGFR1 showed a weak immunoreactivity in the stroma and in basal epithelial cells. FGFR1 showed a weak immunoreactivity in the stroma and in basal epithelial cells. FGFR2 exhibited strong stromal immunoreactivity, becoming weaker in the basal epithelium. No differences were seen in the expression of both receptors between the groups of treated and untreated patients. CONCLUSIONS: A marked reduction in bFGF levels is seen in BPH treated with finasteride in comparison to untreated BPH. In our opinion, finasteride may act as a negative regulator of bFGF expression, counteracting the role of bFGF in the development of BPH.

Cost-effectiveness analysis of tropisetron vs. chlorpromazine-dexamethasone in the control of acute emesis induced by highly emetogenic chemotherapy in children.

OBJECTIVE: To perform a cost-effectiveness analysis (CEA) between a standard antiemetic regimen-chlorpromazine + dexamethasone (CPM-DEX)- and a 5-HT3 receptor antagonist-tropisetron (TROP)--in the control of acute emesis induced by highly emetogenic chemotherapy in children, considering two analytic perspectives: hospital and patients. METHODS: The CEA was performed by constructing a decision tree, for both analytic perspectives, of the possible outcomes of treatment with TROP (single 0.2 mg/kg i.v.) or CPM (5-15 mg i.v. infusion for 3 doses) plus DEX (2 mg/m2 i.v. bolus i.v. x2). The patients were stratified by age in two groups (2-12 and 13-17). To estimate the probability of each endpoint at the decision tree we have taken as a base a trial developed in the Department of Pediatrics. Direct medical cost of primary therapy, failure, complications and side effects were included in the cost calculations. RESULTS: From patients' analytic perspective, TROP was more cost-effective than CPM-DEX for both groups of patients. Discrepancy between both analytic perspectives in 13-17 year-old patient's group was resolved in favour of the option chosen from the patients' analytic perspective (TROP). Sensitivity analysis showed the reliability of the results. CONCLUSIONS: 1. TROP was more cost-effective than CPM-DEX. 2. Taking into account the patients' analytic perspective is essential when we compare antiemetics pharmacoeconomically. 3. It seems necessary to increase the effectiveness of TROP in pediatric patients receiving highly emetogenic chemotherapy with strategies such as the addition of a steroid.

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.

Economic evaluation of Viaflex with vial adapter in a unit-dose drug distribution system.

The cost of parenteral admixtures has an important impact on the hospital budget. Recently, a Viaflex with vial adapter (named 'minibag plus' in some countries) has been commercialized in order to facilitate parenteral admixture preparation. In the present study a preparation using Viaflex with a vial adapter has been economically compared with a preparation with a traditional Viaflex (without adapter) in a centralized unit or in nursing wards in a unit-dose drug distribution system. A cost-analysis was conducted from the hospital point of view. Direct costs were considered: these included supplies and human resources. Differences in the whole process between the two types of Viaflex were analysed. The process included: purchasing, reception, storage, medical order record, preparation in the Pharmacy Service (PS), delivery from the PS to the nursing unit, preparation by the nurse, return of unused material to the PS. Human resource costs were estimated by time counting and multiplying by the average salary. To estimate wasted material, drug and supplies delivered from the PS and returned to the PS were counted during 26 days. With the new Viaflex costs are reduced by 30% in comparison with drug dilution using the traditional Viaflex in a centralized unit of the PS, and by 13.4% in comparison with preparation with the traditional Viaflex in the nursing ward. In addition it can be estimated that contamination risk with the new Viaflex is lower than preparation in the nursing ward with the traditional Viaflex. Therefore, owing to its lower cost we recommend the use of Viaflex with vial adapter for drug dilution for those vials that are compatible with the system.