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Biomedical subjects

N Brion

Publications and source records attributed to N Brion.

At least 19 recordsLinked to original sources
PubMed2000

[Biosphonates in oncology].

MECHANISM OF ACTION: Tumor-induced osteolysis or lytic bone disease is mediated by osteoclast activation. Bisphosphonates inhibit bone resorption by reducing osteoclastic activity. INDICATIONS: Bisphosphonates were shown to be effective in treating cancer-related hypercalcemia. Recent large randomized clinical trials have shown the efficacy of bisphosphonates in reducing bone pain, pathological fractures and spinal cord compression for patients with multiple myeloma and breast cancer metastatic to bone. The potential survival benefit from pamidronate in patients with advanced myeloma warrants further study. FUTURE: Future clinical trials will use more potent bisphosphonates (zoledronate, ibandronate) with the ultimate goal of trying to prevent bone metastases.

Bone Neoplasms↗
PubMed2000

Estradiol pharmacokinetics after transdermal application of patches to postmenopausal women: matrix versus reservoir patches.

OBJECTIVE: A new matrix 17 beta-estradiol transdermal patch incorporating lauric acid to improve estradiol skin absorption has been designed for hormone replacement therapy. Estradiol pharmacokinetics obtained with the prototype, its industrial counterpart, a matrix-type, System 50, and a reservoir-type, Estraderm TTS 50, transdermal patch have been compared. Each device delivers 50 micrograms estradiol daily. METHODS: Twenty postmenopausal women received each of the four formulations for 3 days in a Latin-square design and with a minimum 4-day wash-out period between treatments. Estradiol plasma concentrations were measured by radioimmunoassay at 6, 12, 24, 48 and 72 h after application. RESULTS: The prototype patch and its industrial counterpart showed no significant difference in estradiol delivery, with 72-h systemic exposure to estradiol similar to that of the reservoir patch but greater than that of the reference matrix formulation, with average baseline-corrected concentrations (SEM) of 35 (4), 32 (3), 32 (2) and 19 (1.8) pg/ml, respectively. In addition, they ensured more stable delivery, with coefficients of variation of plasma estradiol concentrations (12-72 h) of 29, 41, 63 and 84%, respectively. All matrix patches demonstrated the same patients to be poor estradiol absorbers, different from those encountered with the reservoir patch type, despite an improved estradiol bioavailability with the lauric acid-containing matrix patch. CONCLUSION: Matrix patches incorporating lauric acid led to estradiol plasma levels more stable than with the reference matrix and reservoir patches, and greater than those with the reference matrix patch.

Administration, Cutaneous↗
PubMed1999

A dose-defining study of sumatriptan suppositories in the acute treatment of migraine.

In this dose-ranging, randomised, multinational, multicentre, double-blind, placebo-controlled, parallel group study, 431 patients treated a single migraine attack with study medication: sumatriptan suppository 6 mg, 12.5 mg, 25 mg, 50 mg, 100 mg, or placebo. Patients were treated in the clinic with a single dose in suppository form. All doses of sumatriptan, except 6 mg, were significantly better than placebo (p < 0.004) and achieved similar rates of headache relief within two hours of dosing. The highest response rate was in the 25 mg group (72%) compared with placebo (37%) (p < 0.001). Fewer patients required rescue medication in the active groups (1% 100 mg to 13% 6 mg) compared with placebo (17%), and more patients were able to work and function normally two hours after dosing (41%, 100 mg; 20%, placebo). The overall incidence of adverse events was similar in the placebo, 6 mg and 12.5 mg groups (14-17%) but higher in the 25 mg, 50 mg and 100 mg groups (25%, 32% and 29% respectively). Analysis of plasma sumatriptan levels indicated rapid rectal absorption for all doses (median tmax = 1.0 hr). It is concluded that sumatriptan, in doses above 6 mg, is an effective and well tolerated treatment for acute migraine. From this study doses of 12.5 mg and 25 mg sumatriptan were identified as having the best efficacy/safety profile and were evaluated further.

Adolescent↗
PubMed1998

[Anticancer chemotherapy. Prevention of complications].

OPTIMAL CHEMOTHERAPY DOSE: The goal of cancer chemotherapy is to eradicate the malignant disease while minimizing severe toxic effects. There is an optimal chemotherapy dose intensity above which palliation is adversely affected by toxicity; below this level the effect is also adverse because of a low rate of tumor response. METHODS FOR REDUCING TOXICITY: There are several methods by which one can reduce the toxicity of cancer chemotherapy, such as the application of rationally designed dosage schedules, alternative routes of administration, biochemical modulation, and the development of drug camers and analogs. Growth factors, interleukins can accelerate the recovery of the hematopoietic cell population after chemotherapy. CHEMOPROTECTORS: Chemoprotectors achieve selective protection of normal tissues. These include mercaptoethanesulfonate (Mesna) for oxazophosphorouros, the cardioprotectant iron chelator, cardioxane, the nucleophilic tripeptide glutathione, and perhaps aminothiolaminofostine. QUALITY OF LIFE: Considerable effort has been made to reduce the negative effect of chemotherapy-induced nausea and vomiting on the quality of life of cancer patients. 5 HT3 receptor antagonist plus dexamethasone led to a significantly higher rate of control of emetic episodes after chemotherapy.

Antidotes↗
PubMed1998

[Glucocorticoids and multiple myeloma. Mechanism of action, resistance and clinical use].

The fundamental and clinical backgrounds for the use of glucocorticoids in multiple myeloma are reviewed. Glucocorticoids induce apoptosis and alter the cellular cycle of malignant cells, interacting with the effects of IL-6. The number of normal or variant glucocorticoid receptors expressed by the tumoral cells and the corticoresistant secretion by stromal cells of IL-6 and its soluble receptor are implicated in resistance to glucocorticoids. Given alone or in association with vincristin and adriamycin, glucocorticoids induce major cytoreduction in tumors and is best used in refractory and relapsing diseases.

Apoptosis↗
PubMed1997

Plasma estradiol concentrations and pharmacokinetics following transdermal application of Menorest 50 or Systen (Evorel) 50.

OBJECTIVES: In order to compare the pharmacokinetics of two transdermal estrogen replacement therapy (ERT) systems designed to release 50 micrograms 17 beta-estradiol/day, two studies were performed in healthy postmenopausal volunteers. METHODS: Both studies had a cross-over design and incorporated a 1-week wash-out period between treatments. In the first study, Menorest 50 and Systen 50 (Evorel 50) were compared over four days of application in 30 women. In the second, 13 women wore each of the two systems for a total of 12 days each (three patches each for 4 days), and comparison was made during the third patch period (steady state, between days 8 and 12). Plasma 17 beta-estradiol levels were assayed using specific direct radioimmunoassays, and pharmacokinetic parameters were calculated by standard methods. All the samples of the first study were re-analysed using a different radioimmunoassay and the results of both assays were compared. RESULTS: In both studies, plasma 17 beta-estradiol levels rose at a comparable rate and reached similar peak levels with each of the two formulations. Levels then remained relatively constant throughout both evaluation periods with Menorest 50, but began to decline after 12 hours in the first study and after 30 h under steady state conditions in the second study with Systen 50. The difference between the two products was statistically significant in both studies. Analysis of pharmacokinetic parameters confirmed the greater bioavailability of Menorest 50. In addition, 17 beta-estradiol levels remained within the suggested therapeutic ranges for relief of acute symptoms and protection against osteoporosis for longer periods of time with Menorest 50 than with Systen 50. CONCLUSION: Since the acute efficacy, long-term protective effects, side effects and risks associated with ERT may depend on critical threshold plasma levels, much attention should be paid to the pharmacokinetic profiles of different formulations. The comparison of these two different radioimmunoassays demonstrates the comparability of their results.

Administration, Cutaneous↗
PubMed1997

Retinoids and metastatic renal cell carcinoma.

The treatment of metastatic renal cell carcinoma remains unsatisfactory. Several therapeutic trials with retinoids and r interferon alpha (r IFN alpha) suggest a synergic antiproliferative effect between retinoid acid and r IFN alpha. Pharmacokinetic data and the mechanism of antiproliferative effects of retinoids are discussed. The induction of growth arrest is related to the expression of specific retinoid receptors. Further investigations are required in order to target the patient population which requires this therapy.

Antineoplastic Agents↗
PubMed1996

[Non-cancer uses of methotrexate].

Methotrexate, used for nearly 40 years as an antimetabolite for cancer therapy, also has indications in dermatology, rheumatology and pneumology. When given at low dosage, it has an antiinflammatory effect although the mechanism is not totally understood. Numerous therapeutic trials have been performed in chronic inflammatory diseases such as rheumatoid arthritis in the adult, juvenile polyarthritis and corticosteroid-dependent asthma. Methotrexate is effective in severe resistant forms of rheumatoid arthritis and is used either alone or in combination with other drugs as first intention therapy because of the good tolerance, patient compliance and ease of use. The beneficial effect in severe corticosteroid-dependent asthma remains to be demonstrated. It has also been used in severe forms of psoriasis and may be useful in other diseases with an autoimmune component. Other less common indications including Crohn's disease, ectopic pregnancy and pregnancy termination require confirmation. Tolerance and compliance are generally good, even for prolonged treatments and undesirable effects are almost always reversible at withdrawal.

Adult↗
PubMed1996

Plasma concentration of estradiol following transdermal administration of Systen 50 or Menorest 50.

Circulating levels of 17 beta estradiol (E2) following the administration of fixed doses of E2, show a great variability in kinetics depending upon the product administrated, the routes of administration, and the interindividual variations in absorption and metabolism. This might have important implications both in terms of tolerance and effectiveness. Two new forms of transdermal E2 (SYSTEN Cilag and MENOREST Rhone-Poulenc Rorer) have been recently accepted in Europe for the treatment of climacteric symptoms. The present study was undertaken to compare the pharmacokinetic characteristics of plasma E2 profile under these two drugs. It was carried out in 30 healthy postmenopausal volunteers according to good clinical practice after informed consent, as a single blind, randomised, cross-over study during the classical wearing period of 4 days. Plasma E2 concentration was determined 24 hours before, 1/2 hour before and then 2, 4, 8, 12, 24, 48, 72, 84, 96 hours after the first patch administration. E2 measurement was performed using a specific direct radioimmunoassay developed in the FRH laboratories. The main criteria for this method were an intraassay coefficient of variation (CV) less than 6%, an interassay CV less than 8% in a concentration range of 15-140 pg/ml and a quantitative detection limit (LOQ) of 2.7 pg/ml with a 20% CV. The following kinetic parameters were analysed: C(max), C(mean), C96 and MRT. The bioequivalence was assessed by analysis of variance of C(max), C(mean), C96 and AuC after logarithmic transformation, complemented by Westlake test (95%). Data show that these two products are identical in terms of C(max) but C(mean), C96 and AuC are statistically greater when MENOREST 50(R) is administered; furthermore, E2 levels decrease more rapidly and more deeply with SYSTEN 50 than MENOREST 50. The differences of pharmacokinetic profiles after administration of two different forms of the same dose of 50 micrograms transdermal 17 beta estradiol might have important medical consequences.

Administration, Cutaneous↗
PubMed1995

Pharmacokinetics of amoxicillin coadministered with a saline-polyethylene glycol solution in healthy volunteers.

The pharmacokinetics of orally administered amoxicillin were investigated in 12 healthy volunteers in a crossover design. They received either a placebo or a saline-polyethylene glycol solution (SPG) for 4 d, the last dose being given simultaneously with 1 g amoxicillin; blood samples were drawn for the next 12 h. Amoxicillin kinetics were similar in the two treatments but small differences in some pharmacokinetic parameters reached significance. The mean +/- SD area under the curve was lower with SPG (43.8 +/- 6.8 against 47.8 +/- 8.2 mg h L-1, p < 0.05) but the treatments were equivalent according to Westlake's test (95% confidence interval = 14.95%). Analysis of SPG against placebo amoxicillin absorption kinetics after fitting the data to a Weibull model revealed a longer duration of the absorption, a slower rate of absorption, and a different shape of the curve. No clinical consequences are expected from these minor variations but possible mechanisms could be relevant to other drugs.

Adult↗
PubMed1995

A population pharmacokinetic study of alminoprofen penetration into synovial fluid.

The pharmacokinetics of alminoprofen in plasma and synovial fluid (SF) at steady state (300 mg t.i.d.) was studied in 45 patients with knee effusion. Plasma and SF samples, one each per patient, were obtained. Six groups were made according to the time of sampling after ingestion of the 13th dose: 1 h (n = 7), 2 h (n = 7), 4 h (n = 7), 6 h (n = 10), 8 h (n = 6), 12 h (n = 8). A three-compartment model was used to describe alminoprofen kinetics in plasma and SF, with two parameterizations, a 'classical' and a 'physiological' one. The non-linear mixed effect model approach was used to estimate the mean and variance of the pharmacokinetic parameters. The mean +/- SE of the estimates (coefficient of variation of interindividual variability as a percentage) were volume of distribution, 11.0 +/- 1.711 (12%); elimination rate constant, 0.236 +/- 0.025 h-1 (18%); absorption rate constant 2.80 +/- 0.31 h-1 (464%), clearance of influx into SF, 0.29 +/- 0.14 mL min-1; clearance of efflux into plasma, 0.56 +/- 0.25 mL min-1. These two clearances were not significantly different, which indicates that passive diffusion occurs in both directions. The mean +/- SD alminoprofen concentration versus time curve in plasma and SF at steady state was simulated and showed that the mean +/- SD maximal concentration in SF was 8.1 +/- 6.3 mg L-1 and was obtained 4 h after dose administration.

Absorption↗
PubMed1993

Cefotiam concentrations in the sinus fluid of patients with chronic sinusitis after administration of cefotiam hexetil.

Cefotiam hexetil is a prodrug of cefotiam. The concentrations of cefotiam in plasma and sinus secretions were determined in 18 patients (10 males, 8 females, aged 39.3 +/- 13.0 years) with chronic sinusitis. All patients received two 200 mg oral doses of cefotiam hexetil 12 h apart and were divided into four groups according to the time which elapsed between the last dose and collection of secretion samples. The last dose was given 2 h (group I), 3 h (group II), 4 h (group III) or 6 h (group IV) before sinus puncture. Cefotiam concentrations were measured by high-pressure liquid chromatography and microbiological assay, results being very similar with both methods. Mean concentrations of cefotiam with the standard deviation in sinus exudates were 1.04 +/- 0.60 mg/l at 2 h (n = 6), 1.04 +/- 0.33 mg/l at 3 h (n = 4), 0.75 +/- 0.74 mg/l at 4 h (n = 4) and < 0.10 mg/l at 6 h (n = 4). Mean sinus fluid concentrations were higher than mean plasma concentrations in all groups. These results suggest that cefotiam concentrations higher than the MICs for common pathogens are found in sinus secretions up to 4 h after oral administration of cefotiam hexetil.

Adult↗
PubMed1993

Influence of local radiotherapy on penetration of fluconazole into human saliva.

The pharmacokinetics of fluconazole (50 mg, single oral dose) in saliva and plasma were determined for five healthy subjects and five patients who underwent radiotherapy (dose, > 45 Gy over a 6-week period) in the salivary gland area and suffered from oropharyngeal candidiasis. Saliva was collected after electrical stimulation. Fluconazole was measured by liquid chromatography. From healthy volunteers and patients, saliva and plasma were sampled from 0 to 24 h. Although fluconazole penetration kinetics were significantly slowed down in irradiated patients, saliva concentrations of fluconazole were higher than those in the plasma, except at 1 h. In the postdistribution phase, the saliva/plasma concentration ratio was in the range of 1.2 to 1.4, and there was no significant difference between healthy subjects and patients. The saliva concentration of fluconazole was over 1 mg/liter throughout the entire interval 2 to 24 h after drug intake. From these results, the clinical efficacy of fluconazole for oropharyngeal candidiasis is not expected to be less than that in subjects with normal salivary glands, provided that salivary secretion remains.

Administration, Oral↗
PubMed1993

Pharmacokinetics and bactericidal activities of one 800-milligram dose versus two 400-milligram doses of intravenously administered pefloxacin in healthy volunteers.

Pefloxacin pharmacokinetics and serum bactericidal activities (SBA) against Escherichia coli and Staphylococcus aureus were compared after intravenous infusion of either a single 800-mg dose or twice-daily 400-mg doses into 16 healthy volunteers. Plasma pefloxacin concentrations were measured for up to 60 h, and SBAs were determined 1, 12, and 24 h after the start of the infusion. The mean areas under the concentration-versus-time curve for plasma were not different (138 versus 136 h.mg/liter). The mean clearances, volumes of distribution, and half-lives were also comparable. The mean (+/- standard deviation) maximal concentration after the 800-mg infusion was 12.11 +/- 1.35 versus 6.51 +/- 0.73 mg/liter after the first 400-mg infusion and 7.42 +/- 0.76 mg/liter after the second 400-mg infusion. Mean trough concentrations at 24 h were significantly different: 2.77 +/- 0.63 (800 mg) versus 1.93 +/- 0.49 (400 mg twice) mg/liter (P = 0.0007). Mean SBAs against E. coli after 800 mg of pefloxacin were higher than 1/128 (1 h), 1/32 (12 h), and 1/16 (24 h). Mean SBAs against S. aureus under the same conditions were higher than 1/64 (1 h), 1/16 (12 h), and 1/8 (24 h). Mean SBAs at 1 and 12 h were significantly higher after the 800-mg infusion than after the 400-mg infusion but were similar at 24 h for both regimens. Comparison of SBAs according to National Committee for Clinical Laboratory Standards criteria showed a similar adequacy at 24 h for both regimens against both strains. Administration of 800 mg of pefloxacin once a day is bioequivalent to 400 mg twice a day, and bactericidal activity of the 800-mg infusion is not less than that of two 400-mg infusions.

Adult↗
PubMed1992

Effect of a macrolide (spiramycin) on the pharmacokinetics of L-dopa and carbidopa in healthy volunteers.

In one well-equilibrated parkinsonian patient treated with combined L-dopa and carbidopa (Sinemet), we have observed changes in treatment efficacy while receiving spiramycin (Rovamycine) for an intercurrent respiratory infection. A preliminary study of the pharmacokinetics of L-dopa and its main metabolites 3-O-methyldopa (3-OMD) and dihydroxyphenylacetic acid (dopac) in two parkinsonian patients treated with Sinemet has revealed a marked decrease in the AUC0-360 of these two metabolites after a 3-day course of Rovamycine. In order to confirm this interaction, we have studied the modifications of the pharmacokinetics of L-dopa, 3-OMD, dopac, and carbidopa in eight male healthy volunteers after a single dose of Sinemet 250 (L-dopa, 250 mg and carbidopa, 25 mg) before and after a 3-day course of Rovamycine. Our study confirms this interaction. After spiramycin, we observed a marked reduction in AUC0-360 for L-dopa (p less than 0.001), 3-OMD (p less than 0.001), and carbidopa (p less than 0.001), and an increase in AUC0-360 for dopac (p less than 0.01). The L-dopa elimination half-life was increased (p less than 0.012); differences in peak plasma concentrations did not attain statistical significance. We think that these modifications in L-dopa pharmacokinetics after spiramycin are due to nonabsorption of carbidopa secondary to modified gastrointestinal motility.

Adult↗
PubMed1992

[Pulmonary and bronchial kinetics of cefuroxime after a single 500 mg intramuscular injection].

Thirty-two patients (28 males; mean age 56 +/- 10 years) who were undergoing bronchopulmonary exeresis surgery were included in this study of the pulmonary (pulm), bronchial (br), and plasma (pl) kinetics of cefuroxime after a single 500 mg intramuscular injection. Twenty-nine bronchial specimens and 38 pulmonary and plasma specimens were taken on average at the following times after the cefuroxime injection: 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 10 h. Cefuroxime was assayed using HPLC on ground tissues, with a correction for contamination by blood. Peak concentrations (C) were found after one hour (Cpl = 11.6 +/- 0.8 micrograms/ml; Cpulm = 7.3 +/- 3.3 micrograms/g; Cbr = 3.7 +/- 1.5 micrograms/g) with the following residual values after 8 hours: Cpl = 0.94 +/- 1.04 micrograms/ml, Cpulm = 0.49 +/- 0.45 micrograms/g, Cbr = 0.15 +/- 0.07 micrograms/g (means +/- 1 SD). Elimination kinetics were monoexponential and similar in plasma, lung tissue and bronchial tissue (elimination half-lives: 1.74 h, 1.66 h, and 1.56 h, respectively), suggesting that all three elements belong to the same pharmacokinetic compartment. Mean intrapolated area-under-the-curve values (AUC) were 33.58 micrograms.ml-1.h (plasma), 20.08 micrograms.g-1.h (lung), and 10.22 micrograms/g-1.h (bronchus). The AUCpulm/AUCpl and AUCbr/AUCpl ratios were 0.60 and 0.30, respectively, in agreement with mean values of tissue level/simultaneous plasma level ratios (lung: 0.59; bronchus: 0.33).

Adult↗