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Biomedical subjects

N Brion

Publications and source records attributed to N Brion.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Right atrial extension of an embryonal carcinoma of the testis.

A case of embryonal carcinoma of the testis extending into the inferior vena cava and the right atrium is presented. Tumor extension was demonstrated preoperatively by computed axial tomography. Successful resection of the intravascular and right atrial extension was achieved using extracorporeal circulation. It is concluded that intravascular and right atrial extension is not a contraindication to radical surgery. This type of metastasis raises the same therapeutic and prognostic problems as those raised by tumor masses in the lungs or lymph nodes found after chemotherapy for malignant nonseminomatous germ cell tumor of the testis.

Adult↗
PubMed1990

Comparison of the 5-hydroxytryptamine3 (serotonin) antagonist ondansetron (GR 38032F) with high-dose metoclopramide in the control of cisplatin-induced emesis.

To compare ondansetron (GR 38032F), a 5-hydroxytryptamine3-receptor antagonist, with metoclopramide in the prophylaxis of acute cisplatin-induced emesis, we conducted a double-blind crossover study in 97 patients scheduled to receive cisplatin (80 to 100 mg per square meter of body-surface area) for treatment of cancer. None had received chemotherapy before this trial. Among the 76 patients who satisfactorily completed both parts of the study, complete or nearly complete control of emesis (i.e., no episodes of emesis occurred, or only one or two) was achieved in 57 of 76 treatments (75 percent) with ondansetron and in 32 of 76 treatments (42 percent) with metoclopramide (P less than 0.001). Ondansetron was also more effective in controlling acute nausea, as assessed with a visual-analogue scale (P = 0.019) or a graded scale (P = 0.024). There was a significant preference among patients for ondansetron (55 vs. 26 percent; P = 0.006). Dystonic reactions were observed during three treatments with metoclopramide; both agents were otherwise well tolerated. We conclude that ondansetron is more effective than metoclopramide in the control of cisplatin-induced nausea and vomiting, and that this suggests that serotonin is an important mediator of this side effect.

Adult↗
PubMed1989

[Pharmacokinetic interaction of cefixime and 2 antacids. Preliminary results].

A crossover study was undertaken in 8 healthy volunteers to evaluate the pharmacokinetics of cefixime administered orally alone or combined with an antacid. Each subject received successively: cefixime alone, Maalox followed 30 min later by cefixime, then Maalox followed 4 hours later by cefixime and finally Alka-Seltzer followed 30 min later by cefixime. Sixteen blood samples were drawn from 0 to 24 hours after oral administration, and plasma cefixime parameters were determined, using a HPLC assay. Four parameters were used to detect a possible interaction: Cmax, Tmax, AUCO-N and AUCO-alpha. No significant difference was observed between the four parameters. Thus, poor absorption of cefixime when combined with an antacid can be ruled out.

Adult↗
PubMed1989

GR38032F, a 5HT3 receptor antagonist, in the prophylaxis of acute cisplatin-induced nausea and vomiting.

A total of 28 patients receiving cancer chemotherapy with cisplatin-containing regimens (70-120 mg/m2) participated in an evaluation of the efficacy and safety of GR38032F for the prevention of acute nausea and vomiting. GR38032F, a 5HT3 receptor antagonist, was given 30 min prior to cisplatin as an 8-mg loading dose by i.v. infusion over 15 min, followed by continuous infusion at a rate of 1 mg/h for 24 h. Efficacy was assessed by measurement of the number of episodes of retching and vomiting occurring in the 24 h after cisplatin administration and by an assessment of nausea during the same period. In all, 26 patients were evaluable for efficacy: overall, complete control was achieved in 12 patients (46%), major control (1-2 emetic episodes), in 6 (23%); minor control (3-5 episodes), in 1 (4%); control could not be achieved (failure; greater than 5 episodes) in 7 patients (27%). GR3832F was the tolerated, with no significant drug-related adverse events. These encouraging results should be confirmed in comparative trials.

Adult↗
PubMed1989

Lack of effect of terfenadine on theophylline pharmacokinetics and metabolism in normal subjects.

The pharmacokinetics of oral theophylline (250 mg) and the production of its metabolites (3-methylxanthine, 1-methyluric acid, 1,3-dimethyluric acid) were studied before and after the administration of oral terfenadine (120 mg twice daily for 16 days) in 10 healthy volunteers. Comparison of volumes of distribution, elimination half-lives, areas under the plasma concentration-time curves, plasma clearance of theophylline and elimination of theophylline metabolites indicated that terfenadine had no significant effect on theophylline pharmacokinetics and metabolism.

Adult↗
PubMed1989

Initial clinical experience with the use of subcutaneous GR43175 in treating acute migraine.

Subcutaneous GR43175 was examined in patients with acute migraine for efficacy, tolerability and safety in an open, controlled, dose-ranging study. Ten patients with acute, non-medicated, migraine (15 attacks) were assessed for severity of headache and associated symptoms (nausea, vomiting and photophobia). GR43175 plasma samples were monitored serially after dosing. Doses of 2 mg or 3 mg gave rapid relief of all migraine symptoms. Thirteen attacks (86%) had either resolved completely or improved to a mild non-migraine residual headache within 40 min. Treatment was well tolerated at all doses, the only adverse effects being transient pain on injection. Peak plasma concentrations were obtained within 10-20 min; a decline in plasma drug concentration did not result in a relapse in headache severity.

Adult↗
PubMed1989

Remission of autoimmune hemolytic anemia associated with chronic lymphocytic leukemia following splenic irradiation.

A 56-year old woman with chronic lymphocytic leukemia associated with corticosteroid-resistant autoimmune hemolytic anemia was successfully treated with splenic irradiation. Cobalt 60 in the dose of 8 Gy was delivered to the spleen, considered sufficient for therapy of B lymphocyte CALLA-phenotype. There has been no recurrence of autoimmune hemolytic anemia over a follow-up period of 28 months. The mechanism of action of splenic irradiation is discussed. This treatment might offer a simple and effective alternative to splenectomy in patients with steroid-resistant hemolytic anemia when surgical operation is contraindicated or refused.

Anemia, Hemolytic, Autoimmune↗
PubMed1989

[Antibiotic prophylaxis in cardiac surgery in France].

Prophylactic administration of antibiotics in patients undergoing cardiac surgery is now an established procedure. The interest of a short prophylaxis (less then 48 h), directed mainly against Gram positive cocci has been demonstrated. However, there is no general agreement as to the agent to be used. We thus conducted a survey of the current practice of antibiotic prophylaxis (ABP) by sending a detailed questionnaire to each of the 51 centers performing cardiac surgery in France. 48 replies (94%) were received. Monotherapy was used in 42 centers, with cephalosporins in 41 (cefamandole: 22, cefazolin: 10, cefuroxime: 4, cephalothin: 3, cefotiam: 2) and with minocycline in one center. Six centers used a combination including aminoglycoside. Mean duration of ABP was 1.8 +/- 1.2 d. First dose of antibiotic was given before cardiopulmonary (C-P) bypass intravenously. In 29 centers, AB was injected into the C-P pump. Mean dosage of cephalosporin before surgery was 25 mg/kg and total dosage was 70 mg/kg/24 h. We conclude that cephalosporins are almost exclusively chosen in France contrasting with other european countries such as the United Kingdom where the most used regimen is a combination of penicillinase-resistant penicillin and an aminoglycoside.

Aminoglycosides↗
PubMed1988

[Comparative serum pharmacokinetics of prednisone and prednisolone methylsulfobenzoate after oral administration].

Pharmacokinetic values of prednisone and prednisolone were measured in the serum of 6 healthy volunteers after oral administration of either prednisolone methylsulfobenzoate 30 mg or prednisone 30 mg. Peak serum concentrations of prednisolone obtained after dosing with prednisone occurred earlier and were higher (473 +/- 106 ng/ml) than those obtained after dosing with prednisolone methylsulfobenzoate (232 +/- 70 ng/ml; P less than 0.01). Similarly, areas under the 0-8 h concentration curves were significantly greater after dosing with prednisone than after dosing with prednisolone methylsulfobenzoate (prednisolone: P less than 0.001; prednisone: P less than 0.02). The differences may be due to prednisolone methylsulfobenzoate not being absorbed as well as prednisone. These kinetic data may warrant a reappraisal of the therapeutic equivalence of the two drugs taken for granted in France.

Administration, Oral↗
PubMed1988

Evaluation of the antimuscarinic activity of atropine, terfenadine and mequitazine in healthy volunteers.

1 The anticholinergic effects of atropine and two antihistamines (terfenadine and mequitazine) were investigated vs placebo in a double-blind study. 2 Salivary secretion, basal pupil diameter, pilocarpine (0.25%) induced miosis and heart rate were determined in eight healthy volunteers, seven male and one female, aged between 23 and 35 years. Each volunteer received all four separate courses of treatment: i.e. terfenadine 60 mg or mequitazine 5 mg twice daily for 3 days, and one single dose on the day of the trial; for the placebo or atropine courses they received the placebo twice daily during 3 days and, on the morning of test day, either the placebo again or atropine 1 mg. Pupillary diameter was measured under standardized conditions using a pupil gauge (Smith and Nephew Pharmaceuticals Ltd). 3 Atropine significantly reduced salivary output (-2.25 +/- 0.36 ml from control values of 4.17 +/- 0.42 ml, P less than 0.001) and heart rate (-9.7 +/- 3.7 beats min-1 from 77.5 +/- 2.7, P less than 0.05). These maximal effects were observed 3 h after atropine dosing for salivary secretion and 1 h for heart rate. Atropine did not affect basal pupil diameter or pilocarpine-induced miosis. 4 Mequitazine and terfenadine did not affect salivary flow, heart rate or pilocarpine-induced miosis. 5 Terfenadine and mequitazine had no anticholinergic effect in these tests involving a limited number of subjects.

Adult↗
PubMed1988

Community-acquired pneumonia. Importance of initial noninvasive bacteriologic and radiographic investigations.

During a one-year epidemiologic survey of acute community-acquired pneumonia, we prospectively investigated in 116 adult nonimmunocompromised patients (a) the importance of initial noninvasive investigations (ie, blood culture and quantitative sputum culture) and the value of the initial radiologic type of pneumonia in diagnosing of the etiologic agent, and (b) the management of pneumonia. Quantitative sputum culture or blood culture (or both) permitted bacteriologic diagnosis in 44 percent of the cases. The radiologic types found were segmental or alveolar densities in 75 patients (65 percent), patchy alveolar densities in 11 (9 percent), mixed opacities in 26 (22 percent), and interstitial infiltrates in four (3 percent). We observed that (a) the prognosis was identical whether a bacteriologic diagnosis was made or not, (b) the Gram stain, an inexpensive procedure, was as contributive for bacteriologic diagnosis as quantitative sputum culture, diagnosis as (c) blood cultures were poorly contributive in patients without severe infections, and (d) alveolar densities were associated with a bacterial infection in 90 percent of the cases of known etiology. On the basis of these results, a pragmatic strategy of initial management of community-acquired pneumonia is proposed.

Adult↗
PubMed1988

Enhancement of the therapeutic effect of cephalosporins in experimental endocarditis by altering their pharmacokinetics with diclofenac.

We studied the effect of a nonsteroidal anti-inflammatory drug, diclofenac, in rabbits on the kinetics of three cephalosporins: cefotiam, cefmenoxime and ceftriaxone, and compared the antibacterial effect of these antibiotics, given alone or with diclofenac, in experimental endocarditis. Diclofenac significantly increased (P less than .05) the area under the curve in tissue-cage fluid of ceftriaxone and cefotiam-treated animals, and the terminal half-life of ceftriaxone in their sera (3.45 +/- 0.4 vs. 2.8 +/- 0.5 hr). Diclofenac reduced urinary excretion of cefotiam only. Cefmenoxime pharmacokinetics remained unchanged by diclofenac. The alteration of ceftriaxone kinetics appeared to be due to nonrenal mechanisms and could suggest reduction of biliary excretion. In Escherichia coli endocarditis, diclofenac enhanced the concentration (P less than .05) of cefotiam (23 +/- 16 vs. 8.9 +/- 5 micrograms/g) and ceftriaxone (13.2 +/- 3 vs. 8.5 +/- 4 micrograms/g) in infected vegetations, but not that of cefmenoxime. The antibacterial effect of ceftriaxone increased with diclofenac (5.5 +/- 1 vs. 7.2 +/- 1 log10 colony forming unit/g of vegetation). In vitro, neither protein binding to rabbit serum proteins nor intrinsic activity on the E. coli strain of each antibiotic was modified by diclofenac. These results suggest that anti-inflammatory drugs could increase antibiotic efficacy by altering their pharmacokinetics. The renal and nonrenal site of interaction may be involved for drugs belonging to the same class. Results obtained in tissue-cage fluid were predictive of the interference at the infected site.

Animals↗
PubMed1988

[Transcutaneous trinitrine. Calling into question the efficacy and innocousness of its use in facilitating venous approach].

Seven infants aged 6 days to 9 months were tested for the use by rubbing of a pomade containing 1 mg trinitrine. The study was interrupted because of high blood passage of trinitrine. The authors emphasize the difficulty of any comparison with the use of this drug in adults. They indicate that there was no clinically appreciable side-effect but they advise to delay, until further studies, the use of this technique, with the only objective of improving the technique of intravenous injections or sampling.

Administration, Cutaneous↗
PubMed1987

Value of antibiotic levels in serum and cardiac vegetations for predicting antibacterial effect of ceftriaxone in experimental Escherichia coli endocarditis.

In a rabbit model of Escherichia coli endocarditis, we studied the penetration into infected vegetations and the antibacterial effect of ceftriaxone. Ceftriaxone was given at different dosages, alone or with an interfering agent, diclofenac, a nonsteroidal anti-inflammatory drug, to determine the predictive value of the antibiotic levels in serum or infected vegetations on the antibacterial efficacy. Diclofenac increased the serum terminal half-life of ceftriaxone and increased its extravascular diffusion in tissue cage fluid, as well as in infected vegetations, allowing us to obtain various antibiotic concentrations in the infected site. Two hours after the fourth injection, around the time of peak level in serum, we observed a linear relationship between (i) serum and local antibiotic levels in vegetations, (ii) local antibiotic levels in a range of 142 to 600 X MBC and bacterial titer (log10 CFU/g) in vegetations, and (iii) serum antibiotic levels in a range of 800 to 1,400X MBC and bacterial titer in vegetations. In vivo, antibacterial effect was obtained only with high antibiotic levels in vegetations (greater than or equal to 220X MBC). This was confirmed by incubating vegetations sampled from infected animals in rabbit serum containing ceftriaxone (ex vivo experiment). Given once daily at a therapeutic dosage (30 mg/kg) for 4 days, ceftriaxone exhibited good efficacy (log10 CFU/g of vegetation = 2.41 +/- 2.7 versus 7.41 +/- 0.92 in control animals) and prevented regrowth of bacteria until 24 h after the last injection. We concluded that (i) provided the dose is sufficient, a long-acting cephalosporin can prove effective in severe gram-negative infections even when given infrequently, and (ii) serum antibiotic levels around the peak value, reflecting high effective local levels, could predict the therapeutic efficacy and represent a simple test to monitor the clinical course of a severe infectious process.

Animals↗