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Biomedical subjects

F Péhourcq

Publications and source records attributed to F Péhourcq.

At least 19 recordsLinked to original sources
PubMed2004

HPLC microdetermination of flurbiprofen enantiomers in plasma with a glycopeptide-type chiral stationary phase column.

A rapid and stereospecific HPLC micromethod to quantify flurbiprofen enantiomers was developed. Both flurbiprofen enantiomers and indomethacin, used as internal standard, were extracted with methylene chloride from 100 microL of acidified plasma. The resolution of the R- and S-forms was performed on a bonded vancomycin chiral stationary phase (Chirobiotic V) with 20% of tetrahydrofuran in ammonium nitrate (100 mM, pH 5) as mobile phase. Calibration curves were linear in the range 0.5-10 microg/mL for both enantiomers. A good accuracy (< or = 5%) was obtained for all quality controls, with intra-day and inter-day variation coefficients equal or less than 7.7%. Recovery of both enantiomers was found in the range 77.4-86.3%. The lower limit of quantitation was 0.25 microg/mL for both enantiomers, without interference of endogenous components. This validated micromethod has been successfully applied for quantifying R- flurbiprofen and S- flurbiprofen in rat plasma.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Rapid high-performance liquid chromatographic measurement of buspirone in human plasma after overdose.

For toxicological purposes, a rapid reversed-phase high-performance liquid chromatographic method was developed for the determination of the anxiolytic drug, buspirone, in human plasma. A liquid-liquid procedure was used to extract this compound from plasma in the presence of an internal standard, quinupramine. The analysis was performed on a Spherisorb S5 C8 analytical column with UV detection at 240 nm. No endogenous compounds were found to interfere. A linear response was observed over the concentration range 5-100 ng/mL. A good accuracy (bias < or =7.9%) was achieved for all quality controls, with intra-day and inter-day variation coefficients equal or less than 7.6%. The limit of quantification was 5 ng/mL. Stability of buspirone in plasma stored at different temperatures was checked. This rapid method (run time <12 min) was used to manage an acute poisoning involving buspirone.

Buspirone↗
PubMed2004

Direct injection HPLC micro method for the determination of voriconazole in plasma using an internal surface reversed-phase column.

A direct plasma injection liquid chromatographic method has been developed for the determination of a new triazole antifungal agent, voriconazole, using an internal surface reversed phase column. Therapeutic drug monitoring of voriconazole is relevant for patient management, especially in the case of drug-drug interaction. The method is easy to perform and requires 10 microL of a plasma sample. The chromatographic run time is less than 9 min using a mobile phase of 17:83 v/v acetonitrile-potassium dihydrogen phosphate buffer, 100 mM, pH 6.0 and UV detection at 255 nm. The fl ow rate was 1 microL/min. A linear response was observed over the concentration range 0.5-10 microg/mL (r2 = 0.977). A good accuracy (bias < or = 7.5%) was achieved for all quality controls, with intra-day and inter-day variation coefficients inferior to 6.7%. The lower limit of quantitation was 0.2 microg/mL, without interference of endogenous components. The stability of voriconazole in plasma stored at different temperatures was checked. Finally, the possibility of direct injection of plasma samples into the column permits a reduction in reagent consumption and in analytical steps, and hence in analytical error.

Antifungal Agents↗
PubMed2004

[Pharmacokinetics in the elderly].

Physiological changes that occur in the aging process may directly affect drug pharmacokinetics. In the absence of disease or other pathologic conditions, age-related changes in pharmacokinetics principally affect drug absorption, distribution, metabolism or elimination. One factor that does change consistently with age is renal clearance, consequently a common pharmacokinetic change is reduced drug clearance, especially for drugs excreted largely unchanged by the kidneys. Alteration of the pharmacokinetics of drugs in the elderly may necessitate adjustment of dosages to prevent toxicity or inadequate therapy. As a broad generalization, dosage should be reduced in elderly patients, reflecting the general decline in body function with age.

Absorption↗
PubMed2003

Rapid high-performance liquid chromatographic measurement of amisulpride in human plasma: application to manage acute intoxication.

Amisulpride, a substituted benzamide derivative, is a second-generation (atypical) antipsychotic and is effective as maintenance therapy in patients with schizophrenia. For toxicological purpose, a rapid RP-HPLC assay was developed for the determination of amisulpride in human plasma. A linear response was observed over the concentration range 100-1000 ng/ml. A good accuracy (< or =5%) was achieved for all quality controls, with intra- and inter-day variation coefficients equal or inferior to 4.9%. The lower limit of quantification was 20 ng/ml, without interferences of endogenous components. This rapid method (run time <5 min) was used to monitor eight intoxications involving amisulpride.

Amisulpride↗
PubMed2003

High-performance liquid chromatographic method with diode array detection to identify and quantify atypical antipsychotics and haloperidol in plasma after overdose.

For toxicological purposes, an HPLC assay was developed for the simultaneous determination of haloperidol and atypical antipsychotics (risperidone, 9-hydroxyrisperidone, olanzapine, clozapine) in human plasma. After a double-step liquid-liquid extraction, compounds were separated on a C(8) column eluted with a gradient of acetonitrile and phosphate buffer 50 mM pH 3.8. A sequential ultraviolet detection was used (260, 280 and 240 nm). Calibration curves were linear in the range 10-1000 ng/ml. The limits of quantification were 5 ng/ml for all drugs. Average accuracy at four concentrations ranged from 93 to 109%. Both inter- and intra-day variation coefficients were lower than 11% for all drugs. This simple and rapid method (run time<15 min) is currently used for poison management.

Antipsychotic Agents↗
PubMed2002

Influence of a polymeric formulation of ketoprofen on its diffusion into cerebrospinal fluid in rats.

Poly(D,L)lactide nanocapsules (NCs) have been proposed as an alternative carrier for many drugs. We investigated the influence of this formulation on the pharmacokinetics of ketoprofen in the plasma and cerebrospinal fluid (CSF). Male Wistar rats were given intraperitoneal dose of ketoprofen (5 mg/kg) in a suspension of NCs or in a carboxymethylcellulose (CMC) solution (reference preparation). Blood and CSF samples were collected at different times up to 24 h after dosing. The unbound fraction of ketoprofen in plasma (f(u)) was determined using ultrafiltration. The total (C(T)) and free (C(F)) concentrations of ketoprofen in plasma and the simultaneous CSF concentrations (C(CSF)) were measured by a HPLC method and the areas under the curve (AUC(T), AUC(F), AUC(CSF)) were calculated. AUC(T) of ketoprofen-loaded NCs in plasma was similar to that of the reference solution, while AUC(F) of the former (5.41 mg/l x h) was higher than that produced by the latter (4.03 mg/l x h). Accordingly, the unbound fraction (f(u)) was higher after administration of NCs than that of the solution (2.5 and 1.8%, respectively). Finally, AUC(CSF) were identical for both formulations. These findings suggest that the binding of ketoprofen to plasma proteins is not the major factor that governs its blood-to-CSF exchanges.

Animals↗
PubMed2002

[Pharmacokinetics in the elderly].

Physiological changes that occur in the aging process may directly affect drug pharmacokinetics. In the absence of disease or other pathologic conditions, age-related changes in pharmacokinetics principally affect drug absorption, distribution, metabolism or elimination. One factor that does change consistently with age is renal clearance, consequently a common pharmacokinetic change is reduced drug clearance, especially for drugs excreted largely unchanged by the kidneys. Alteration of the pharmacokinetics of drugs in the elderly may necessitate adjustment of dosages to prevent toxicity or inadequate therapy. As a broad generalization, dosage should be reduced in elderly patients, reflecting the general decline in body function with age.

Absorption↗
PubMed2001

Chiral resolution of flurbiprofen and ketoprofen enantiomers by HPLC on a glycopeptide-type column chiral stationary phase.

Vancomycin is an amphoteric, glycopeptide, macrocyclic antibiotic. When attached to 5 microspherical silica gel, vancomycin proved to be an effective chromatographic chiral stationary phase that could be used in the reversed-phase mode. In this study, a bonded vancomycin chiral stationary phase (Chirobiotic Vtrade mark) was investigated for the chiral liquid chromatography analysis of ketoprofen and flurbiprofen. The selectivity factor (alpha) and the chiral resolution factor (RS) of Chirobiotic Vtrade mark were evaluated first as a function of the buffer pH and molarity, and second as a function of organic modifier type and composition of the mobile phase. Four organic modifiers (tetrahydrofuran, 2-propanol, 1,4-dioxane and methanol) have been tested for their selectivity. Optimized conditions using 20% of tetrahydrofuran in ammonium nitrate (100 mM, pH 5) were selected for the enantioseparation of flurbiprofen and ketoprofen from their racemic forms. At pH 5, these acidic compounds are almost negatively charged, while the chiral selector possesses a positive charge allowing it to interact electrostatistically with the analytes. Using these chromatographic conditions, the column stability was excellent over several months of experiments.

Buffers↗
PubMed2001

In vitro distribution of ketoprofen enantiomers in articular tissues of osteoarthritic patients.

The distribution of ketoprofen enantiomers in joint tissues was studied as a function of their relative tissular affinities using the multi-chamber distribution dialysis system described by Bickel et al. Selected off-cuts of synovial membrane, joint capsule, cartilage and ligament were obtained from ten patients suffering from osteoarthritis of the knee (n=3) or hip (n=7). Sörensen solution (4 ml) spiked with racemic ketoprofen (2 microg ml(-1)) was dialysed against 1 ml of the four solutions of tissue homogenates (0.4 g ml(-1)). Ketoprofen enantiomers were quantified in buffer and tissue solutions by high-performance liquid chromatography. The distribution of ketoprofen enantiomers in the Bickel's multi-compartment model indicated that there was a non-stereoselective affinity of ketoprofen enantiomers for their potential target tissues. Despite the interindividual variability in articular tissues, the concentrations (+/-S.D.) of R- and S-ketoprofen were significantly higher in synovial membrane (8.69 (4.76) microg g(-1) for S, 9.14 (5.57) microg g(-1) for R), joint capsule (5.71 (2.49) microg g(-1) for S, 5.49 (2.62) microg g(-1) for R) and ligament (6.28 (3.61) microg g(-1) for S, 6.40 (3.64) microg g(-1) for R) than in articular cartilage (3.67 (1.75) microg g(-1) for S, 3.70 (1.67) microg g(-1) for R). There were no significant differences in the distribution of R- and S-ketoprofen between the solutions of joint capsule, synovium and ligament tissues. These data may be related to differences in ketoprofen affinity for the different constituents of joints. This in vitro distribution profile is similar to that reported in vivo for other non-steroidal anti-inflammatory drugs.

Adult↗
PubMed2001

Piroxicam concentrations in plasma and synovial fluid after a single dose of piroxicam-beta-cyclodextrin.

AIMS: The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in rheumatic diseases depends on their concentrations within the joint. We determined piroxicam concentrations in plasma and synovial fluid (SF) after a single oral dose of 20 mg in the form of one tablet of piroxicam-beta-cyclodextrin. METHODS: 45 patients, aged 21 to 84 years, presenting with an effusion of the knee, related to degenerative or inflammatory joint disease, were included in this study after having given their written consent. One blood and one SF sample were drawn concomitantly in each patient from 0.5 to 48 h after NSAID administration. Piroxicam assays were performed by high performance liquid chromatography. Pharmacokinetic parameters were obtained from the mean plasma and synovial concentrations measured at various sampling times. RESULTS: The peak concentration was higher in plasma (2.51+/-0.25 microg/ml) than in SF (1.31+/-0.76 microg/ml), but the elimination half-life was much longer in SF (90.7 h) than in plasma (32.5 h). The SF/plasma area under the concentration-time curve ratio (evaluating the quantity of NSAID transferred from the blood to the joint) was equal to 0.39. CONCLUSIONS: Piroxicam contained in piroxicam-beta-cyclodextrin diffused well into the SF where its pharmacokinetic profile corresponded to that of a long half-life NSAID.

Administration, Oral↗
PubMed1999

Influence of molecular lipophilicity on the diffusion of arylpropionate non-steroidal anti-inflammatory drugs into the cerebrospinal fluid.

The diffusion of seven arylpropionic acid non-steroidal anti-inflammatory drugs (NSAIDs) into the cerebrospinal fluid (CSF) has been investigated in male Wistar rats by means of quantitative structure-activity relationship (QSAR) study. After intraperitoneal administration of each drug (5 mg/kg), blood and CSF samples were collected at different times (0.5, 1, 3, and 6 h). The fraction bound to plasma proteins (fb) was determined using ultracentrifugation. The total (CT) and free (CF) plasma concentrations and the concentrations in CSF (CCSF) were measured by a reversed-phase high performance liquid chromatographic (RP-HPLC) method. The areas under the curve of the free plasma (AUCF) and CSF (AUCCSF) concentrations were calculated according to the trapezoidal rule. The overall drug transit into CSF was estimated by the ratio RAUC (AUCCSF: AUCF). The lipophilicity of the compounds was expressed as their polycratic capacity factors (log k'w) measured in a RP-HPLC system. The RAUC ranged from 0.24 to 6.58 and fb from 91.4 to 99.8%. The compounds with an intermediate lipophilicity value (3 < logk'w < 3.6) easily entered the CSF (RAUC > 1). A parabolic relationship was found between log k'w and log RAUC, emphasizing the role of molecular lipophilicity in the diffusion into CSF. Considering the fb value of each drug in regard to this non-linear relationship, it can be hypothesized that the diffusion rate of NSAIDs into the CSF depends primarily on the lipophilicity.

Animals↗
PubMed1998

Determination of third-generation cephalosporins by high-performance liquid chromatography in connection with pharmacokinetic studies.

The third-generation cephalosporins are semisynthetic beta-lactam antibiotics, including several oral and parental agents with extended activity against Gram-negative pathogens. They are generally determined either by microbiological techniques or by high-performance liquid chromatography (HPLC). The major drawback or bioassays is the lack of specificity, especially when a biotransformation of the cephalosporin molecule leads to active metabolites, or when the antibacterial therapy is based on association with drugs. Thus, for many years, numerous reversed-phase HPLC procedures have been proposed to overcome these difficulties. This review presents different HPLC methods proposed for the quantification in biological fluids of fourteen third-generation cephalosporins, ranged between parenteral and oral compounds. The sensitivity and specificity of these chromatographic procedures are discussed with regard to the pharmacokinetic properties of the antibiotics studied.

Animals↗
PubMed1997

Relationship between lipophilicity and binding to human serum albumin of arylpropionic acid non-steroidal anti-inflammatory drugs.

A possible relationship between lipophilicity and binding to human serum albumin was investigated for 11 arylpropionate non-steroidal anti-inflammatory drugs. The lipophilic parameter was determined by a reversed-phase high-performance liquid chromatographic procedure as the capacity factor (k'). The binding of arylpropionic acids to human serum albumin was studied in vitro by equilibrium dialysis. For each compound, a Scatchard analysis was performed considering two classes of binding sites characterized by high- and low-affinity constants, K1 and K2, respectively. A linear relationship was found between lipophilicity and binding parameters, n1K1 (r = 0.88, P < 0.0005) and n2K2 (r = 0.96, P < 0.0002). These results suggest the role of hydrophobic interactions in the binding of arylpropionic acids to human serum albumin.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Prednisolone concentrations in cerebrospinal fluid after oral prednisone. Preliminary data.

Penetration of prednisolone across the blood-brain barrier was studied in 17 patients (ten women and seven men) with a mean age of 64 +/- 17 years admitted for nerve root pain warranting a lumbar puncture. One blood sample and one cerebrospinal fluid sample were obtained concomitantly from each patient, two hours (n = 7), four hours (n = 5) or six hours (n = 5) after an oral dose of 40 mg of prednisone. Prednisolone was assayed in all samples using high performance liquid chromatography and its binding to plasma proteins was determined using ultrafiltration. Total plasma prednisolone levels declined over time from 597 +/- 174 ng/ml two hours post-dose to 422 +/- 106 ng/ml four hours post-dose and 250 +/- 85 ng/ml six hours post-dose. Plasma levels of free prednisolone were 95 +/- 21 ng/ml, 59 +/- 17 ng/ml, and 18 +/- 14 ng/ml, respectively, at the same time points. Prednisolone was detectable in all cerebrospinal fluid samples, in levels of 14 +/- 2 ng/ml after two hours, 29 +/- 9 ng/ml after four hours and 17 +/- 7 ng/ml after six hours. These data demonstrate that equilibration of plasma and cerebrospinal fluid levels is achieved after six hours.

Administration, Oral↗
PubMed1996

Influence of lipophilicity on the diffusion of cephalosporins into the cerebrospinal fluid.

The aim of this quantitative structure-activity relationship (QSAR) study was to investigate the influence of lipophilicity on the diffusion of cephalosporins into the cerebrospinal fluid (CSF). The lipophilicity was expressed as the chromatographic capacity factor (log k'w) determined by high-performance liquid chromatography in a reversed-phase system. The penetration of eight cephalosporins into CSF was studied in male Wistar rats receiving the drugs intramuscularly (1.5 mg/kg). One hour after administration, CSF and blood samples were collected, and concentrations of free drug were measured in CSF (CCSF) and in plasma (CP). A significant parabolic relationship was sought between lipophilicity (log k'w) and the capacity of diffusion across the blood-brain barrier expressed as log (CCSF/CP). The cephalosporins exhibiting a moderate lipophilicity diffused well into CSF. A pharmacokinetic study was performed at 1, 2 and 4 h after administration of three cephalosporins: cefazolin, ceftriaxone and cefsulodin. These compounds were choosen according to their lipophilicities (low, moderate and high values, respectively). The AUC0-4h for both free plasma (AUCP) and cerebrospinal fluid (AUCCSF) concentrations were determined. The AUCCSF/AUCP ratio presented a maximum value for a strongly albumin bound cephalosporin, ceftriaxone. In our experimental conditions, the ideal lipophilicity (log k'w) range for diffusion of cephalosporins from plasma into CSF was between 1.6 and 1.8.

Animals↗