PubMed Health⌕ Search

Biomedical subjects

B Diquet

Publications and source records attributed to B Diquet.

At least 55 records · Page 3Linked to original sources
PubMed1993

Clinical pharmacokinetics of zidovudine: inter and intraindividual variability and relationship to long term efficacy and toxicity.

The variability of the pharmacokinetics of zidovudine after its oral administration to 36 AIDS patients has been investigated by measuring the plasma and urine levels of zidovudine and its metabolite on Days 1 and 35 of continuous treatment. A two-phase absorption model was first defined from well-documented data in 12 subjects. The population characteristics of the kinetic parameters for both days were estimated by a nonparametric method. On Day 1, the mean (coefficient of variation) volume of distribution of zidovudine was 94.41 (90%), its mean half-life was 0.81 h (107%) and its mean oral clearance was 117 l.h-1 (57%) and on Day 35, these values were, respectively, 1121 (139%), 0.75 h (181%) and 295 l.h-1 (196%). The results confirm the large interindividual and intraindividual variation in zidovudine kinetics. The four covariates included in the population analysis (body weight, serum haemoglobin, creatinine and bilirubin) did not show clear relationship to the kinetic parameters. Thirty-four subjects were follow-up clinically for 99 days to 367 days after initiation of zidovudine therapy. The relationship between individual kinetic parameters (determined by Bayesian estimation), mean concentration profiles and outcome was studied through survival analysis. Long-term efficacy was defined as the prevention of opportunistic infections, which occurred in 13 patients. No clinical or kinetic variables, nor the individual zidovudine concentration profiles were found to predict the occurrence of an opportunistic infection. Toxicity was defined as a 20%-decrease in serum haemoglobin, which occurred in 13 patients. A significant relationship between mean daily concentration and toxicity was found, with an hazard of occurrence of toxicity 4.3-times larger when the mean steady stade concentration was 0.8 mg.l-1 than 0.6. The results indicate that zidovudine dosage should be individualised.

AIDS-Related Complex↗
PubMed1993

Comparative study of availability of prednisolone after intestinal infusion of prednisolone metasulfobenzoate and prednisone.

The role of intestinal absorption in the differential availability of prednisone (PN) and prednisolone metasulfobenzoate (PO-MS), which might account for clinical resistance to PO-MS, has been studied by an infusion technique. In a randomized cross-over design trial, a solution in isotonic saline of PN or PO-MS (115 mg.l-1 was infused at 5 ml.min-1 for 2 h, into a 25 cm segment of jejunum in 8 healthy fasting subjects. The intestinal content was partly collected and the flow rate at the end of the test segment was determined by using a water movement marker (PEG 4000). Plasma, intestinal and urine concentrations of PN and PO were determined by liquid chromatography. From the data on PO, the active molecule, the systemic availability of PO-MS was significantly smaller than of PN, with the respective mean AUCs being 1.71 and 3.60 mg.h-1. The difference was associated with smaller mean Cmax, 0.20 vs 0.64 mg.l-1, higher mean tmax, 2.94 vs 2.06 h and lower mean ka, 0.98 vs 2.18 l/h after PO-MS. No significant difference was found in the half-life or renal clearance of the formulations tested. The mean MRT was significantly increased after PO-MS, 6.82 vs 5.30 h. The observed difference probably reflected a difference in intestinal absorption. The mean absorption in the test segment of PO-MS was significantly smaller at 17.4 vs 85.5% for PN. The ester form may be a limiting factor in the intestinal absorption of PO.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Benzodiazepines reverse the anti-immobility effect of antidepressants in the forced swimming test in mice.

The present study provides evidence that, in mice subjected to the forced swimming test, the anti-immobility effect of the tricyclic antidepressants, desipramine and imipramine (16-32 mg/kg) was antagonized by the acute co-administration of a benzodiazepine, diazepam (0.25-2 mg/kg) and lorazepam (0.125 mg/kg). This effect cannot be accounted for by variations in plasma and/or brain levels of each compound since brain and plasma concentrations of desipramine and plasma levels of diazepam and desmethyldiazepam, measured immediately after the swimming test, were not significantly modified by the co-administration. Diazepam (2 mg/kg) also counteracted the reduction of time spent immobile induced by the MAO inhibitors, toloxatone (256 mg/kg) and selegiline (4 mg/kg) and the 5-HT1A receptor agonist, 8-OH-DPAT (1 mg/kg), but not by the psychostimulant, caffeine (32 mg/kg). The sedative neuroleptic, thioridazine (4 mg/kg) was also found to reverse the anti-immobility effect of desipramine whereas the non-benzodiazepine anxiolytics, alpidem (8 mg/kg) and buspirone (0.5 mg/kg) did not. These results indicate that the observed interactions were unlikely to be accounted for by a reduction of the stressful aspect of the situation whereas the participation of some motor or sedative component could not be totally ruled out.

Analysis of Variance↗
PubMed1992

Sensitive micromethod for column liquid chromatographic determination of fluoxetine and norfluoxetine in human plasma.

A rapid, selective and sensitive micromethod has been developed for the determination of fluoxetine (FLU) and its demethylated metabolite norfluoxetine (N-FLU) using a 250-microliters plasma sample and column liquid chromatography with ultraviolet detection at 226 nm. The limit of detection is 2.0 ng/ml for both FLU and N-FLU. Peak-height ratios are linear over a concentration range of 10-800 and 10-1000 ng/ml for FLU and N-FLU, respectively. Acceptable coefficients of variation are demonstrated for both within-run and day-to-day assays. Selected drugs were checked for interference. The method, which requires a very small volume of plasma, is sensitive enough for pharmacokinetic studies in animals, clinical pharmacology studies and drug monitoring in children or adult patients.

Chromatography, Liquid↗
PubMed1991

Sensitive one-step extraction procedure for column liquid chromatographic determination of fluvoxamine in human and rat plasma.

A normal-phase column liquid chromatographic assay for fluvoxamine, a recently introduced atypical antidepressant, has been developed. Prior to analysis, aliquots of alkalinized plasma were extracted with n-hexane. These extracts were then injected into a 5-microns Resolve spherical silica column. Fluvoxamine and the internal standard, clovoxamine, were detected at a wavelength of 254 nm. Standard curves were linear over the concentration range 2-400 ng/ml. Acceptable coefficients of variation were obtained for both within-run and day-to-day studies. The estimated limit of detection is 0.5 ng/ml, and selected drugs checked for coadministration show no analytical interference. This assay was used to evaluate the pharmacokinetics of fluvoxamine in rats.

Animals↗
PubMed1991

Virological markers in the cerebrospinal fluid from HIV-1-infected individuals.

We analysed 127 specimens of cerebrospinal fluid (CSF) from 118 HIV-1-infected individuals at different stages of infection. Intrathecal antibody synthesis was evident in 23 samples tested and was more frequently directed against HIV than against rubella virus, herpes simplex virus, varicella zoster virus or cytomegalovirus. HIV was isolated from only 14% of the 127 CSF specimens, but from 82% of CSF-paired blood samples. HIV antigen was detected in 12% of CSF specimens and 44% of paired plasma samples. Twenty specimens analysed using the polymerase chain reaction (PCR) detected proviral DNA in 75% of CSF specimens. The low rate of virus recovery from CSF was caused by neither the freezing of specimens prior to culture nor therapy. In contrast, virus isolation from CSF was significantly associated with CSF cell count. Virus isolation and antigen detection in CSF were not correlated with either the Centers for Disease Control disease stage or the peripheral CD4+ lymphocyte count, whereas viraemia was significantly associated with a low CD4+ lymphocyte count. Moreover, virus isolation and antigen detection in CSF were not associated with symptoms of subacute HIV encephalitis, suggesting that these markers are not of potential value in the diagnosis of HIV-specific neurologic complications. The value of PCR in this field merits further investigation.

AIDS Dementia Complex↗
PubMed1991

Pharmacokinetics of primaquine in healthy volunteers.

The pharmacokinetics of primaquine were investigated in 8 healthy subjects (4 males and 4 females). The volunteers received 15 mg base of primaquine daily for 14 days. The results showed that the concentration-time profiles in whole blood and in plasma were similar. The mean values (+/- SD) of area under the curve (AUC) of the last dose were significantly decreased when compared to the values of the first dose both in whole blood and in plasma (909.96 +/- 603.07, 1,147.05 +/- 684.8 ng.hr/ml respectively in whole blood with p = 0.007 and 1,255.11 +/- 531.59, 1,603.66 +/- 505.45 ng.hr/ml respectively in plasma with p = 0.023). The decrease in the concentration-time profile of the last dose was due to enhancement of drug elimination with significant increase in clearance after the last dose (4.871 +/- 1.741 and 6.443 +/- 2.514 ml/min/kg respectively in whole blood with p = 0.007, 3.199 +/- 1.197 and 4.422 +/- 2.068 ml/min/kg respectively in plasma with p = 0.016).

Absorption↗
PubMed1991

Pharmacokinetics of prednisone and prednisolone in bullous pemphigoid patients.

The purpose of this prospective study was to attempt to evaluate a possible relationship between corticosteroids pharmacokinetics parameters and clinical efficacy in bullous pemphigoid (BP) patients. Sixteen BP patients took part in the study. Prednisone (Cortancyl, Laboratoire Roussel) was given orally (1 mg/kg/day) in a single morning dose. Eleven blood samples were collected over 24 h for the pharmacokinetic studies on day 1 (first day of treatment) and on day Y (after the clinical evaluation). Efficacy was evaluated as the number of new skin blisters on day 1 and on day X which was either the day of cure, i.e. no blisters (responders), or the day of treatment failure, i.e. persistence of blisters (non-responders). Prednisolone (PO) was assayed using high-performance liquid chromatography (HPLC). Areas under the plasma concentration time curves (AUC) and plasma half-lives were estimated using a model independent approach. In responder patients, PO AUC values were 6,225.5 +/- 575.5 ngh/ml, range 3,933-9,080.5 on day 1 and 5,687 +/- 535 ngh/ml, range 4,513.5-9,828.5 on day Y. There was a significant correlation (0.87) between the number of skin blisters on day 1 and the time required for their resolution. The pharmacokinetics and clinical data suggest that a "therapeutic" AUC value was necessary to achieve clinical efficacy and that the duration of treatment depended on the number of blisters on day 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Lack of interaction between disulfiram and alprazolam in alcoholic patients.

Certain interactions between disulfiram and benzodiazepines, especially diazepam and chlordiazepoxide, have previously been reported. The influence of disulfiram on the pharmacokinetics of alprazolam, a triazolobenzodiazepine, metabolized by hepatic microsomal oxidation, has been evaluated in 11 chronic alcoholic patients (6 males, 5 females) undergoing treatment for the alcohol withdrawal syndrome. Each patient received alprazolam 2 mg on the first day (control) followed by two weeks of treatment with disulfiram 0.5 g/d, and then further oral dose of alprazolam 2 mg. No significant change was found in any of the kinetic parameters. Thus, a therapeutic dose of disulfiram did not significantly alter the clearance or half-life of alprazolam in chronic alcoholic patients.

Adult↗
PubMed1990

Self-inhibiting action of nortriptyline's anti-immobility effect at high plasma and brain levels in mice.

Animals were treated acutely with 0, 2.5, 5, 10, 20 and 40 mg/kg nortriptyline (NT) 30 min before the tail suspension test (TST). They were sacrificed after test for evaluation of plasma and brain levels of NT. The anti-immobility effect increased with increasing doses and concentrations of the drug, reaching statistical significance (P less than 0.01, Dunnett test) at a dose of 20 mg/kg, 865 ng/ml in plasma and 11 micrograms/g in brain tissue. The anti-immobility effect was, however, blocked with the highest, non-toxic, concentrations. Results seem to indicate a biphasic curvilinear relationship between plasma and brain levels of NT and behaviour in mice.

Animals↗
PubMed1990

[Cross resistance to mefloquine and halofantrine in a case of P. falciparum malaria contracted in Sierra Leone].

Malaria caused by P. falciparum occurred during prophylaxis with mefloquine upon return from Sierra Leone (zone II). A typical and not recognized, with negative results of initial hematological examinations. Diagnosed on D.26 with parasitemia of 0.2%. Successful treatment of clinical symptoms with halofantrine but increased anemia and positive parasitemia at D.7. Successful treatment with chloroquine. Chemosensitivity tests confirmed sensitivity to chloroquine, threshold sensitivity to quinine (IC50 = 297), resistance to mefloquine (IC50 = 76) despite high levels in bloods, and to halofantrine (IC50 = 7-laboratory normal value = 1). This cross-resistance of P. falciparum originating from Sierra Leone to mefloquine-halofantrine seems to be the first observation of this danger in Africa. Prescription of chloroquine is still imperative in zone 11 countries.

Adult↗
PubMed1990

[Pharmacokinetic parameters of prednisone and prednisolone in healthy volunteers].

A cross-over, double-blind, randomized trial with 8 healthy volunteers was undertaken to compare prednisolone and prednisone pharmacokinetics after a single oral dose (1 mg/kg) of prednisone (Cortancyl) and prednisolone sodium metasulfobenzoate (Solupred). Maximum prednisolone concentrations measured after ingestion of prednisone are higher (535 +/- 32 ng/ml) and occur earlier than after taking prednisolone sodium metasulfobenzoate (198 +/- 114 ng/ml) (p less than 0.001). The areas under the curve are significantly larger after prednisone than after prednisolone sodium metasulfobenzoate (p less than 0.02). These findings suggest a decreased systemic availability of prednisolone after prednisolone sodium metasulfobenzoate (Solupred) administration and show, from a strictly pharmacokinetic point of view, that equimolar doses of prednisone and prednisolone sodium metasulfobenzoate are not equivalent therapies.

Adult↗