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Biomedical subjects

F Bressolle

Publications and source records attributed to F Bressolle.

At least 19 recordsLinked to original sources
PubMed2006

Stability of amphotericin B and nystatin in antifungal mouthrinses containing sodium hydrogen carbonate.

Amphotericin B and nystatin are two polyene antibiotics that are potent antifungal agents. These drugs are active against most pathogenic fungi like Aspergillus and Candida. Mouthrinses containing these drugs are used for preventive and curative treatment of fungal infections like oral candidiasis, which can cause multiple diseases in cancer patients. Because there were no marketed antifungal mouthrinses available, their preparations were performed at the hospital and town pharmacies. To date, there are no data available on the stability of both these drugs in the form of mouthrinses. Therefore, each mouthrinse had to be prepared extemporaneously. The aim of this study was to investigate the stability of amphotericin B (Fungizone) and nystatin (Mycostatine) in the form of mouthrinses containing 1.4% sodium hydrogen carbonate. The stability of these solutions was tested at different temperatures (4-37 degrees C) with or without electric- or sunlight exposure and in two types of containers (glass and polypropylene) over a 15-day period. The admixtures were also monitored for colour change and pH. Amphotericin B and nystatin were quantified by high-performance liquid chromatography. At 4 degrees C, amphotericin B and nystatin were stable for 15 days in polypropylene. When stored in polypropylene at room temperature, with or without light protection, amphotericin B and nystatin were stable for 3 and 4 days, respectively.

Amphotericin B↗
PubMed2005

Population pharmacokinetics of mycophenolic acid in kidney transplant pediatric and adolescent patients.

Current data on mycophenolate mofetil (MMF) suggest that there is a pharmacokinetic/pharmacodynamic relationship between the mycophenolic acid (MPA) area under the curve (AUC) during treatment and both the risk of acute rejection and the occurrence of side effects. The aim of this study was to characterize the population pharmacokinetics of MPA in kidney transplant patients between the ages of 2 and 21 years and to propose a limited sampling strategy to estimate individual MPA AUCs. Forty-one patients received long-term oral MMF continuous therapy as part of a triple immunosuppressive regimen, which also included cyclosporine or tacrolimus (n=3) and corticosteroids. Therapy was initiated at a dose of 600 mg/m twice daily. The population parameters were calculated from an initial group of 32 patients. The data were analyzed by nonlinear mixed-effect modeling using a 2-compartment structural model with first-order absorption and a lag time. The interindividual variability in the initial volume of distribution was partially explained by the fact that this parameter was weight-dependent. Fifteen concentration-time profiles from 13 patients were used to evaluate the predictive performance of the Bayesian approach and to devise a limited sampling strategy. The protocol, involving two sampling times, 1 and 4 hours after oral administration, allows the precise and accurate determination of MPA AUCs (bias -0.9 microg.h/mL; precision 6.02 microg.h/mL). The results of this study combine the relationships between the pharmacokinetic parameters of MPA and patient covariates, which may be useful for dose adjustment, with a convenient sampling procedure that may aid in optimizing pediatric patient care.

Adolescent↗
PubMed2004

Simultaneous determination of dexamethasone and 6 beta-hydroxydexamethasone in urine using solid-phase extraction and liquid chromatography: applications to in vivo measurement of cytochrome P450 3A4 activity.

It has been demonstrated that the formation of the hydrophilic metabolites of dexamethasone, 6 alpha- and 6 beta-hydroxydexamethasone, correlated with cytochrome P450 (CYP) 3A4 enzyme levels. So, the 6 beta-hydroxydexamethasone/dexamethasone urinary ratio could be a specific marker for human CYP3A4 activity. We have developed a sensitive and specific high-performance liquid chromatographic method for the simultaneous quantification of urinary free dexamethasone and 6 beta-hydroxydexamethasone using 6 alpha-methylprednisolone as internal standard. This method involved a solid phase extraction of the three compounds from urine using Oasis HLB Waters cartridges with an elution solvent of ethyl acetate (2 ml) followed by diethyl ether (1 ml). Separation of the three analytes was achieved within 24 min using a reversed-phase Nova-Pak C(18) analytical column (4 microm, 300 mm x 3.9 mm i.d.). An ultraviolet detector operated at 245 nm was used with a linear response observed from 10 to 100 ng/ml for dexamethasone and from 25 to 1000 ng/ml for 6 beta-hydroxydexamethasone. Obtained from the method validation, inter-assay precision was below 15% and accuracy ranged from 95.7 to 110%. The extraction efficiency of the assay was approximately of 99% and was constant across the calibration range. The lower limit of quantitation was 10 ng/ml for dexamethasone and 25 ng/ml for 6 beta-hydroxydexamethasone; at these levels, precision was below 16% and accuracy was 99-109%. This method was applied to in vivo measure of the CYP3A4 activity.

Chromatography, Liquid↗
PubMed2003

Pharmacokinetic-pharmacodynamic modelling of recombinant human erythropoietin in athletes.

The aim of this study was to develop a pharmacokinetic model that takes into account the negative feedback loop of endogenous erythropoietin production observed after repeated recombinant human erythropoietin administration. A pharmacodynamic data analysis was performed using the changes in i) reticulocyte count, ii) serum levels of soluble transferrin receptors, and iii) soluble transferrin receptors/serum proteins ratio as an index of the therapeutic effect of the hormone. Nine athletes were included in the study; they received repeated subcutaneous administrations (50 IU x kg(-1) per day) of recombinant human erythropoietin. The mean half-life of the terminal part of the curve was 35.5 h, and the total clearance was 17 ml x h(-1) x kg(-1). The total clearance was about two times higher in athletes than in untrained subjects (5.5 - 7.5 ml x h(-1) x kg(-1)) and the half-life period of plasma erythropoietin after subcutaneous administration was five times longer compared to intravenous administration (4 to 7 h). Thus, after subcutaneous administration, the terminal part of the curve should correspond to the absorption phase, instead of to the elimination phase (flip-flop phenomenon). The pharmacodynamic relationship based on a sigmoid Emax model can be reasonably used to relate the changes observed in the markers to recombinant human erythropoietin administration. Recombinant human erythropoietin induces a delayed increase in reticulocytosis and in soluble transferrin receptor levels. In comparison with baseline, the increase of these markers became significant from the third and the tenth day after the initial administration of the hormone, respectively. These results were in accordance with the equilibration delay computed from the pharmacokinetic-pharmacodynamic data modelling (half-life of 25.7 h and 10 days, respectively). The recombinant hormone was well tolerated during this study.

Adult↗
PubMed2003

Population pharmacokinetics of ciprofloxacin in pediatric and adolescent patients with acute infections.

The aim of the present study was to characterize the population pharmacokinetics of ciprofloxacin in patients with and without cystic fibrosis ranging in age from 1 day to 24 years and to propose a limited sampling strategy to estimate individual pharmacokinetic parameters. Patients were divided into four groups according to the treatment schedule. They received ciprofloxacin by intravenous infusion (30 min) or by the oral route. The number of samples collected from each patient ranged from 1 to 12. The population parameters were computed for an initial group of 37 patients. The data were analyzed by nonlinear mixed-effect modeling by use of a two-compartment structural model. The interindividual variability in clearance (CL) was partially explained by a dependence on age and the patient's clinical status. In addition, a significant relationship was found between weight and the initial volume of distribution. Eighteen additional patients were used for model validation and evaluation of limited sampling strategies. When ciprofloxacin was administered intravenously, sampling at a single point (12 h after the start of infusion) allowed the precise and accurate estimation of CL and the elimination half-life, as well as the ciprofloxacin concentration at the end of the infusion. It should be noted that to take into account the presence of a lag time after oral administration, a schedule based on two sampling times of 1 and 12 h is needed. The results of this study combine relationships between ciprofloxacin pharmacokinetic parameters and patient covariates that may be useful for dose adjustment and a convenient sampling procedure that can be used for further studies.

Acute Disease↗
PubMed2003

Is whole body impedance a predictor of blood viscosity?

Bioelectrical impedancemetry (BIA) has received a widespread interest as a non-invasive approach to body fluid volumes. Since similar techniques have been studied to assess in vitro rheological properties of blood, we investigated the relationships between whole body impedance and blood viscosity parameters in order to determine possible predictive equations. 30 sportsmen (24.6+/-1.01 years; 73.96+/-1.62 kg; 177.73+/-1.33 cm) were enrolled into the study. Body composition was assessed with a multifrequency bioelectrical impedancemeter (Dietosystem Human IM Scan) using low intensity at the following frequencies: 1, 5, 10, 50 and 100 kHz. Viscometric measurements were done at 1000 s(-1) with a falling ball viscometer (MT 90 Medicatest). Hematocrit (Hct) was measured with microcentrifuge. A standardized exercise test was performed on a cycloergometer during 25 minutes. Physical working capacity (W170) was calculated and VO2max was evaluated with Astrand nomograms. Two hemorheological parameters were independently correlated with impedance (Z) measurements: whole blood viscosity (WBV) at 100 kHz (r=0.518; p=0.01) and Hct at 1 kHz (r=-0.485; p=0.01). Plasma viscosity was correlated multilinearly with water/fat free mass and Z at 10 kHz (r=0.441; p=0.02). In addition both WBV and Z at 100 kHz exhibited correlations with aerobic working capacity (VO2max ) with r=-0.482 and r=-0.475 (p</=0.05), respectively. A stepwise regression analysis selects Z at 100 kHz instead of WBV as a predictor of VO2max. These findings confirm our previous reports about relationships between whole body conductance for high frequency and aerobic working capacity and suggest a new approach for non-invasive evaluation of blood rheology with BIA.

Adult↗
PubMed2003

Reduction of red blood cell disaggregability during submaximal exercise: relationship with fibrinogen levels.

Effects of exercise on erythrocyte aggregation were investigated in 19 elite athletes. High shear rate viscometry (1000 s(-1) evidenced an increase in blood viscosity explained by an increase in hematocrit (+8% p<0.01) and plasma viscosity (+7% p<0.01). Erythrocyte rigidity index and erythrocyte aggregability measured using the Myrenne erythroaggregometer did not change. However, using the laser backscattering technique (SEFAM erythroaggregometer), we observed significant changes in aggregability and desaggregability after 25 min of exercise. The initial aggregation time (TA) decreased by 33% (p<0.01), while the final aggregation time decreased by 13.6% (p<0.01). TA was correlated with aerobic working capacity (r=0.73; p=0.005), which was negatively correlated with blood viscosity at rest (r=-0.57; p=0.043). A significant relationship was observed between TA and the initial fibrinogen levels (r=0.71; p<0.01). The plasma volume contraction during exercise was found to be statistically explained by the water loss proportional to the total work load. Thus, laser backscattering demonstrates an increase in aggregability and a decrease in disaggregability of red cells during exercise, proportional to baseline fibrinogen values.

Adult↗
PubMed2003

Is the feeling of heavy legs in overtrained athletes related to impaired hemorheology?

The feeling of having "heavy legs" (FHL) is commonly reported in the overtraining syndrome (OTS), i.e., the condition wherein an athlete is training excessively, yet performance deteriorates. Since FHL is also a sign of chronic venous insufficiency where it can be corrected by rheo-active drugs, and given the fact that OTS is also a hemorheologic disease associated with mild hemoconcentration, we investigated whether the FHL is associated with a hemorheologic profile. 37 athletes training 13.05+/-0.97 hr/week completed the French questionnaire of Overtraining (mean score: 11.66+/-1.96) and underwent a medical check-up including hemorheological measurements. 14 subjects quote the item: "I have the FHL". Although well matched with the 23 others for age and body composition, FHL subjects had higher plasma viscosity (1.44+/-0.05 vs 1.32+/-0.02 mPa.s; p<0.05) and a higher red cell aggregation as measured with laser backscattering (Affibio indices: final aggregation time "TF": 36.77+/-1.88 vs 44.26+/-2.37; p<0.05; aggregation index at 10 s "S10": 26.31+/-1.14 vs 21.92+/-1.19; p<0.05). The OTS score was correlated positively with plasma viscosity (r=0.549; p=0.008), whole blood viscosity (r=0.4458; p=0.03), and the following aggregability parameters: "S10" (r=0.4818; p=0.0232) and the aggregation index at 60 s "S60" (r=0.4601; p=0.0312). The OTS score was also correlated negatively with the aggregability parameters "TF" (r=-0.4432; p=0.0389) and the initial aggregation time "TA" (exponential relationship r=-0.458; p=0.03). These findings suggest that the feeling of heavy legs in overtrained athletes is related to OTS-related hemorheologic disturbances, namely mild plasma hyperviscosity and mild erythrocyte hyperaggregability.

Adult↗
PubMed2003

Hemorheological correlates of fitness and unfitness in athletes: moving beyond the apparent "paradox of hematocrit"?

UNLABELLED: Negative correlations between blood viscosity parameters and fitness have been reported, but their physiological meaning remains incompletely understood. Since rheo-active treatments are used in athletes doping, we aimed at clarifying the relationships between hematocrit (Hct), viscosity and performance by comparing aerobic capacity, overtraining questionnaire, and hemorheological parameters. SUBJECTS AND METHODS: 29 sportsmen (24.71+/-1.05 yr; 74.90+/-1.44 kg; 178.5+/-1.05 cm) underwent a standardised exercise test. Physical working capacity (W170), maximal power output (Wmax) and maximal oxygen consumption (VO2max ) were calculated. Viscometric measurements were done with a MT 90 Medicatest viscosimeter. Hct was measured with microcentrifuge. All subjects answered the overtraining questionnaire proposed by the French Society for Sports Medicine. RESULTS: The best correlate of maximal power output (Wmax) was whole blood viscosity (r=-0.383, p<0.001). The stepwise regression analysis only selected Hct as W170 determinant (r=-0.66, p<0.001). Similarly the best determinant of VO2max, expressed as a percentage of theoretical values, was Hct (r=-0.462, p=0.01). Hct/viscosity ratio (Hct/eta), a proposed index of Hct's positive influence on O2 transfer to tissues, was positively correlated to Wmax expressed as a percentage of theoretical values (r=0.487, p=0.02). The overtraining score was correlated to plasma viscosity (r=0.450, p=0.016). CONCLUSION: The best hemorheogical correlate of fitness is a low hematocrit and the best hemorheological correlate of overtraining is increased plasma viscosity.

Adult↗
PubMed2002

Influence of food and diabetes on pharmacokinetics of sodium tungstate in rat.

In this paper, the influence of food and diabetes on the pharmacokinetics of sodium tungstate in rat was investigated. The compound was administered intravenously (9 mg/kg) and orally in the form of solution (36 mg/kg). An empirical Bayes methodology was used to compute individual pharmacokinetic parameters. Sodium tungstate followed first-order kinetics, and plasma concentration versus time data were described by a two-compartment model. A significant relationship was found between the bioavailability and the status of the animals. Total plasma clearance and elimination half-life averaged 3.1 ml/min/kg and 1.6 h, respectively. Food had some effects on the extent of sodium tungstate absorption. After oral administration, the bioavailability (0.67 versus 0.85), C(max) (6.10 versus 15.2 microg/ml) and AUC (70.7 versus 105 mgh/l) were 20, 60 and 32% lower in fed than in fasted rats, respectively. The presence of cellulose and sulphate anions in rat chow could partially explain the fed state-associated reduction of tungstate bioavailability. In streptozotocin-induced diabetic fed rats, a 25% decrease occurred in AUC and F, and a 14% increase occurred in the elimination rate constant compared with healthy fed rats. These changes could be explain on the one hand, by the increase of liquid consumption and food intake, and on the other hand, by a gastroparesis in the early diabetic rats.

Animals↗
PubMed2002

Exercise-induced central retinal vein thrombosis: possible involvement of hemorheological disturbances. A case report.

Exercise-induced impairment in blood fluidity has been supposed to increase cardiovascular risk but there is no data to support this hypothesis. We report the case of a 50 yr old marathon runner who underwent a central retinal vein thrombosis after a marathon run. We investigated his rheological response to exercise compared to control subjects of previous studies. During a standardized sub-maximal exercise-test, the increase in blood viscosity (+28%) and hematocrit (+25%) exceeded the control range but the most striking differences were found for red cell aggregation (Myrenne +47%) and disaggregation thresholds (Affibio +37%). Although some of this post-exercise hyperviscosity pattern may be due to the previous vascular event, these findings may also support the hypothesis of a role for hemorheological alterations during exercise in the pathogenesis of this marathon-induced retinal thrombosis, and indicate that after such an event hemorheological adaptation to exercise remains markedly disturbed.

Blood Viscosity↗
PubMed2001

High-performance liquid chromatographic determination of cefepime in human plasma and in urine and dialysis fluid using a column-switching technique.

A high-performance liquid chromatographic method with UV absorbance was developed for the analysis of cefepime in human plasma and urine, and in dialysis fluid. Detection was performed at 280 nm. The assay procedure for cefepime in plasma involves the addition of an internal standard (cefpirome) followed by treatment of the samples with trichloracetic acid, acetonitrile and dichloromethane. To quantify cefepime in diluted urine (1:20) and in the dialysis fluid, samples spiked with the internal standard (cefpirome) were analysed using a column-switching technique. The HPLC column, Nucleosil C18, was equilibrated with an eluent mixture composed of acetonitrile-ammonium acetate (pH 4). Linear detector responses were observed for the calibration curve standards in the range 0.5 to 100 microg/ml, which spans what is currently thought to be the clinically relevant range for cefepime concentrations in body fluids. The limit of quantification was 0.5 microg/ml in the three matrices. Extraction recoveries proved to be more than 84%. Precision, expressed as %RSD, was in the range 1.5 to 9%. Accuracy ranged from 93 to 105%. This method was used to follow the time course of the concentration of cefepime in plasma, urine and dialysate outlet samples after a 10-min infusion period of 2 g of this drug in patients with acute renal failure undergoing hemodiafiltration.

Calibration↗
PubMed2001

Quantitative determination of rocuronium in human plasma by liquid chromatography-electrospray ionization mass spectrometry.

Liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) was used for the quantification of the neuromuscular blocking agent rocuronium in human plasma. Verapamil was used as internal standard. The samples were subjected to a dichloromethane liquid-liquid extraction after ion pairing of the positively charged ammonium compound with iodide prior to LC-MS. Optimized conditions involved separation on a Symmetry Shield RP-18 column (50 x 2.1 mm, 3.5 microm) using a 15-min gradient from 10 to 90% acetonitrile in water containing 0.1% trifluoroacetic acid at 250 microl/min. Linear detector responses for standards were observed from 25 to 2,000 ng/ml. The extraction recovery averaged 59% for rocuronium and 83% for the internal standard. The limit of quantification (LOQ), using 500 microl of plasma, was 25 ng/ml. Precision ranged from 1.3 to 19% (LOQ), and accuracy was between 92 and 112%. In plasma samples, at 20 and 4 degrees C, rocuronium was stable at physiological pH for 4 h; frozen at -30 degrees C it was stable for at least 75 days. The method was found suitable for the analysis of samples collected during pharmacokinetic investigations in humans.

Androstanols↗
PubMed2001

Estimation of pharmacokinetic parameters of sodium tungstate after multiple-dose during preclinical studies in beagle dogs.

In this paper, an empirical Bayes methodology was used to determine the pharmacokinetic profile of sodium tungstate in beagle dogs after multiple oral dosing using the P-PHARM computer program. The population estimation algorithm used in P-PHARM is an EM-type procedure. Sodium tungstate was administered orally, three times a day, (i) for 11 days (21 and 42 mg/kg per day) to 18 dogs (nine males and nine females) and (ii) for 13 weeks (15, 30 and 60 mg/kg per day) to 28 dogs (14 males, 14 females). Six other dogs received the compound intravenously (25 and 50 mg/kg). Plasma concentration profiles versus time were compatible with a two-compartment model and first-order kinetics. After oral administration, F (0.61+/-0.086 vs. 0.48+/-0.093), and normalized (to a 7-mg/kg dose of sodium tungstate) AUC (54+/-8.4 vs. 41.2+/-8.5 mg/l x h), C(max) (10.6+/-0.49 vs. 8.5+/-0.57 microg/ml) and C(min) (3.04+/-0.23 vs. 2.04+/-0.22 microg/ml), were higher in male than in female dogs. However, the introduction of the gender in the final model did not contribute statistically to an improvement of the fit of the population pharmacokinetic model. In males, t(1/2) elimination averaged 3.1+/-0.56 vs. 2.6+/-0.18 h in females. The duration of treatment did not modify statistically the pharmacokinetic parameters. After repeated multiple oral administration of 15-60 mg/kg per day of sodium tungstate, tungsten plasma concentrations increased in proportion to dose. No dose-dependent changes in pharmacokinetic parameters occurred.

Administration, Oral↗
PubMed2001

Salivary and plasma pharmacokinetics of topotecan in patients with metastatic epithelial ovarian cancer.

The comparative saliva/plasma pharmacokinetics of topotecan were investigated in 13 patients with metastatic epithelial ovarian cancer receiving topotecan (30-min intravenous (i.v.) infusion) on a five consecutive day schedule every 3 weeks. During the first and the second courses of treatment, each patient underwent pharmacokinetic evaluation. Quantitation of the total topotecan (lactone plus carboxylate form) was assessed by a highly specific high-performance liquid chromatographic (HPLC) method. Large patient-to-patient variations in the plasma and saliva concentrations were observed. Plasma and saliva pharmacokinetics could be described using a biexponential pattern. From the saliva data, the half-life of the terminal part of the curve was 2.64 h, it was of the same order of magnitude as the topotecan elimination half-life determined from the plasma data, 3.18 h. Topotecan concentrations were higher in the saliva than in the plasma, the saliva/plasma concentration ratio averaged 2.31 and the ratio area under the parotid saliva (AUC(s)) over plasma (AUC(p)) concentration-time curve (AUC(s)/AUC(p)) averaged 2.11. For each individual, a significant relationship was found between topotecan concentrations in the saliva and in the plasma, the coefficients of correlation ranged from 0.75 to 0.92 according to the patient. Myelosuppression, especially granulocytopenia was the most frequent toxicity encountered during the trial. The percent decrease in the leucocyte count, absolute neutrophil count and platelet count were related to the AUCp/day using sigmoidal E(max) models. The high values of the Hill constant found reflect the very steep AUC-haematoxicity relationship observed. In most cases, abdominal pain occurred in patients presenting high saliva concentrations. One patient with high salivary concentrations (mean S/P ratio=4.60) had grade 1 mucositis. In conclusion, the concentration of topotecan in saliva appeared to be useful as an indirect, non-invasive estimation of the levels of topotecan in the plasma; thus, saliva concentrations could be a good predictor of the behaviour of topotecan in the body.

Adult↗
PubMed2001

Pharmacokinetic-pharmacodynamic modeling of atracurium in intensive care patients.

The authors have studied 10 critically ill patients with acute respiratory distress syndrome who required a neuromuscular blocking drug to assist mechanical ventilation. Patients received a bolus dose of 1 mg/kg of atracurium followed by a constant infusion rate of 1 mg/kg/h of this drug for 72 hours. Neuromuscular block was monitored using an accelerograph. Blood samples were obtained over a 96-hour period. A preliminary independent analysis was done to estimate the individual pharmacokinetic parameters; data were consistent with a one-compartment model. The pharmacodynamic data analysis was then performed using the changes in train-of-four (TOF) count as an index of the therapeutic effect of atracurium. Pharmacokinetic-dynamic variables were calculated using the Sheiner model and the Hill equation. The elimination half-life of atracurium averaged 22 minutes. Mean volume of distribution and plasma clearance were 217 ml/kg and 550 ml/min, respectively. There was a significant hysteresis loop when the TOF count was plotted against predicted plasma atracurium concentrations. The mean sigmoidicity factor, gamma, was 4.04. The concentration producing 50% of the Emax was 1.36 micrograms/mL, and the mean ke0 was 0.059 min-1. Recovery time ranged from 30 to 80 minutes, and none of the patients of this study had residual paralysis.

Adult↗
PubMed2000

High-performance liquid chromatographic determination of vinorelbine in human plasma and blood: application to a pharmacokinetic study.

A sensitive and specific high-performance liquid chromatographic method with fluorescence detection (excitation wavelength: 280 nm; emission wavelength: 360 nm) was developed and validated for the determination of vinorelbine in plasma and blood samples. The sample pretreatment procedure involved two liquid-liquid extraction steps. Vinblastine served as the internal standard. The system uses a Spherisorb cyano analytical column (250x4.6 mm I.D.) packed with 5 microm diameter particles as the stationary phase and a mobile phase of acetonitrile-80 mM ammonium acetate (50:50, v/v) adjusted to pH 2.5 with hydrochloric acid. The assay showed linearity from 1 to 100 ng/ml in plasma and from 2.5 to 100 ng/ml in blood. The limits of quantitation were 1 ng/ml and 2.5 ng/ml, respectively. Precision expressed as RSD was in the range 3.9 to 20% (limit of quantitation). Accuracy ranged from 92 to 120%. Extraction recoveries from plasma and blood averaged 101 and 75%, respectively. This method was used to follow the time course of the concentration of vinorelbine in human plasma and blood samples after a 10-min infusion period of 20 mg/m2 of this drug in patients with metastatic cancer.

Aged↗