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J Duchier

Publications and source records attributed to J Duchier.

At least 37 records · Page 2Linked to original sources
PubMed1988

Dose and concentration-effect relations for rilmenidine.

The dose-effect and concentration-effect relations of rilmenidine, a new alpha 2 agonist, were evaluated for the hemodynamic and side-effect responses to single oral doses. Two studies were performed in a double-blind manner: study I in 8 healthy subjects and study II in 10 hypertensive patients. In the course of five 24-hour periods, each separated by at least 1 week, the following 5 treatments were administered in a random order: placebo, rilmenidine (0.5, 1, 2 and 3 mg). Blood pressure was measured with a Roche arteriosonde (study I) or a sphygmomanometer (study II). Sedation was measured using a visual analog scale. Dry mouth was assessed by measuring the salivary flow (study I) or by visual analog scale (study II). Plasma concentration of rilmenidine was assayed by gas chromatography linked with mass spectrometry. The antihypertensive and sedative effects (area under curve) were directly related to the dose and to the log of the plasma concentration of rilmenidine. In contrast to the 2- and 3-mg doses, rilmenidine (0.5 and 1 mg) did not induce orthostatic hypotension, a significant decrease in heart rate or a significant dryness of mouth. At doses of 0.5 and 1 mg, the effects of rilmenidine on sedation were not consistent in both studies: sedation was significant in study I but did not differ from placebo in study II. These studies show that rilmenidine, in common with other alpha 2 agonists, decreases blood pressure in a dose-dependent manner, in normotensive as well as in hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Pharmacokinetics of spiramycin in man.

The pharmacokinetics of spiramycin were studied after single and repeated administration by iv and oral routes. Following iv administration of a 500-mg dose in a one-hour infusion, peak serum concentrations were 1.54-3.10 mg/l. These concentrations are higher than MICs of spiramycin for various infectious agents. Eight hours after the end of infusion, the mean serum concentration was close to 0.25 mg/l. Spiramycin is rapidly and widely distributed throughout the body and achieves high ratios of tissue to serum concentrations in bucco-dental, pulmonary and prostatic tissues and skin. The distribution half-life of spiramycin was 10 min. The steady-state volume of distribution (Vdss) and the tissue distribution volume were 5.6 and 4.5 l/kg. The absolute bioavailability of spiramycin was 36% (S.D. +/- 14). Oral doses of spiramycin between 1 and 2 g resulted in linear increase in the peak serum levels and areas under the serum concentration-time curve. Spiramycin does not appear to undergo important metabolic conversion and is mainly excreted via the biliary route. Indeed, in man, the urinary excretion of active compounds represents only 7.6 to 20% of the administered dose. Spiramycin had a terminal elimination half-life of approximately 5 h. Renal clearance (144 ml/min) was much lower than non-renal clearance (887 ml/min). The total body clearance of spiramycin in young adults was 1.42 l/min (S.D. +/- 0.5) but only 0.53 l/min (S.D. +/- 14) in elderly subjects. During repeated iv administration (500 mg tid), steady state was achieved after four doses. Cmax and Cmin were 3.0 and 0.5 mg/l in young adults and 4.5 and 1.75 mg/l in elderly patients. Spiramycin's kinetics differ in several important respects from erythromycin's, notably the larger volume of distribution of spiramycin which reflects the higher tissue concentration. The reduced spiramycin clearance in elderly subjects requires further investigation.

Administration, Oral↗
PubMed1987

Antihypertensive effect of sustained-release isosorbide dinitrate for isolated systolic systemic hypertension in the elderly.

A double-blind, randomized trial was performed in 40 patients, mean age (+/- standard deviation) 80 +/- 4 years, with isolated systolic systemic hypertension to evaluate the antihypertensive effect of oral sustained-release isosorbide dinitrate (ISDN), 20 to 40 mg twice daily, vs placebo. After 12 weeks of treatment, supine systolic blood pressure (BP) decreased from 192 +/- 10 to 162 +/- 12 mm Hg with ISDN (p less than 0.001) and from 189 +/- 10 to 175 +/- 15 mm Hg with placebo (p less than 0.001). On the basis of variance analysis, the decrease in systolic BP was significantly lower with ISDN (27 mm Hg) than with placebo (13 mm Hg). Similar results were observed for supine and erect systolic BP measured at 8 AM and 4 PM, 8 and 12 hours after drug intake. No significant differences in diastolic BP, heart rate or side effects occurred. After the ISDN tapering off-period (2 weeks), systolic BP increased significantly but did not change with placebo. The study provided evidence that in elderly patients with systolic hypertension, sustained-release ISDN induced a selective and sustained decrease in systolic BP, antihypertensive effect was observed 8 and 12 hours after drug administration, and no tolerance phenomenon was noted.

Aged↗
PubMed1987

Airway response to salbutamol and to ipratropium bromide after non-selective and cardioselective beta-blocker.

Eight healthy men were randomly assigned in a latin square order to receive single doses of placebo, tertatolol 5 mg, propranolol 80 mg and atenolol 100 mg at 7-day intervals. Resting heart rate and pulmonary function were measured 10 min before and over the 240 min following dosing, and then 15 min after inhalation of salbutamol 200 micrograms and ipratropium bromide 40 micrograms. The three beta-blockers caused similar reductions in resting heart rate throughout the study, whereas placebo had no effect. The three beta-blockers, like placebo, produced no significant change in pulmonary function during the 240 min after dosing. The bronchodilator response to salbutamol after atenolol and placebo was preserved, whereas it was reduced after administration of either of the non-selective beta-blockers, tertatolol and propranolol. An unequivocal response of the airways to ipratropium bromide was observed after tertatolol and propranolol, which was much greater than after atenolol. No response was observed after placebo. Thus, despite bronchial beta 2-blockade, by non-selective beta-blockers, bronchodilatation was definitely produced by ipratropium bromide, confirming the predominant role of the parasympathetic system in the autonomic innervation of normal human airways.

Adrenergic beta-Antagonists↗
PubMed1987

Effect of BN 52063, a specific PAF-acether antagonist, on bronchial provocation test to allergens in asthmatic patients. A preliminary study.

Platelet Activating Factor, PAF-acether, elicits acute and more prolonged inflammatory responses in both experimental animals and man, and is recognised as a possible mediator of asthma. The effect of a specific PAF-acether antagonist, BN 52063, on the early asthmatic response to inhaled allergen was assessed in a randomised, double-blind, crossover study in eight atopic asthmatics, who received three days treatment with BN 52063 or placebo, separated by a one week washout. On the third day of treatment, subjects were challenged with nebulised house dust mite or pollen allergen. BN 52063 significantly antagonised early bronchoconstriction and showed a tendency to inhibit residual bronchial hyperreactivity, assessed six hours after allergen challenge by a provocation test to acetylcholine. No side effects were reported during active treatment. This is the first study in man demonstrating the efficacy of a specific PAF-acether antagonist on the immediate response to inhaled allergen challenge in asthmatics. The findings support the possible role of specific PAF-acether antagonists in the treatment of asthma.

Acetylcholine↗
PubMed1987

Prolonged beta blockade due to tertatolol: a comparative study with propranolol and atenolol.

Submaximal exercise heart rate was measured after oral administration of placebo, tertatolol 5 mg, propranolol 80 mg, and atenolol 100 mg to 12 subjects in a double-blind cross-over study. The peaks of beta-blocking activity, observed at 2 hr, were of similar extent for the 3 drugs. The duration of activity of tertatolol, a beta blocker with a short elimination half-life, extended up to 24 hr as did that of atenolol, but was longer than that of propranolol which reached only 18 hr. These results support once-daily administration of tertatolol in therapy.

Adult↗
PubMed1986

Phase II trial with D-Trp-6-LH-RH in prostatic carcinoma: comparison with other hormonal agents.

Various approaches to hormonal treatment of prostate carcinoma are discussed. Eighty-one patients with prostatic carcinoma, eight with stage B, nine with stage C, and 64 with stage D disease, were treated subcutaneously daily for 3 months with the LH-RH agonist D-Trp-6-LH-RH (Decapeptyl) in order to evaluate the incidence of remissions according to WHO recommendations for oncologic trials. The findings were compared to those obtained with other hormonal therapies of prostatic carcinoma according to the statistical method of "expected response rate" as adapted by Lee and Wesley for phase II trials. Treatment with D-Trp-6-LH-RH greatly reduced serum LH and testosterone levels without raising serum prolactin. After 1-2 weeks of therapy, there was relief of subjective symptoms and a reversal of the signs of prostatism as well as a marked decrease in bone pain. At 90 days 52 patients had complete relief of prostatism and 21 had only mild signs and symptoms. Seventy patients were experiencing no bone pain and an additional six had only mild pain. Prostatic size, evaluated by rectal examination and transabdominal ultrasonography, reverted to normal in 26.4% of patients (complete remission) and was reduced by more than 50% in an additional 17.6% (partial remission), the overall rate of complete plus partial regression of prostatic enlargement being 44%. Scans showed a major improvement of bone lesions in 14.8% of cases. This response increased to 37% after more than 6 months of follow-up. Prostatic acid phosphatase levels were decreased by more than 50% in 61% of the patients, but this test appears to be a less valid marker than the lipid-associated sialic acid (LASA). The increase in LASA before treatment and a reduction after treatment can frequently be correlated with the objective volume of the neoplasms. No flare-up of the disease was encountered, and there were no side effects except for impotence. Statistical analyses of results by the method of Lee and Wesley indicated that the incidence of complete and partial regression (CR and PR) observed with D-Trp-6-LH-RH was not significantly different from that recorded in previous studies for another LH-RH analog, Buserelin. However, CR and PR obtained with D-Trp-6-LH-RH (44%) were significantly higher than with subcapsular orchiectomy (22%). Hormonal effects and some other actions of D-Trp-6-LH-RH were compared and contrasted with those produced by castration, estrogens, antiandrogens, and progestogens.(ABSTRACT TRUNCATED AT 400 WORDS)

Acid Phosphatase↗
PubMed1986

Inhibition of PAF-acether induced weal and flare reaction in man by a specific PAF antagonist.

It has been suggested that PAF-acether may be an important mediator in asthma and a PAF antagonist may therefore have a potentially important role. PAF-acether has been shown to induce a dual inflammatory response in the skin of man and we investigated the effect of BN 52063, a PAF antagonist, on this response. At a dose of 80 mg, BN 52063 orally inhibited the inflammatory response to a sub-cutaneous injection of PAF-acether 400 ng. A late cutaneous response was not observed in any of the subjects. BN 52063 was also demonstrated to be well tolerated at doses of 20, 40, 80 and 120 mg with no significant side effects.

Adult↗
PubMed1986

[Treatment of prostatic cancers by periodic administration of a delayed-release preparation of D-Trp(6)-LHRH].

The hormonal effects of a delayed-release intramuscular (IM) preparation of D-Trp-6-LH-RH (TRP-6 microcapsules) were investigated in men aged 65-75 years. Six men with a prostatic adenoma (group A) received subcutaneously (SC) 500 micrograms TRP-6/day from day 0 to day 6. Seven men with a prostatic carcinoma (group B) were given the same SC treatment, but in addition received on days 7, 28 and 56 an intramuscular injection of 3 mg TRP-6 microcapsules. During SC treatment, plasma TRP-6 levels rose to 2-4 ng/ml. Plasma LH peaked on day 1, whereas high testosterone levels were maintained from day 2 to day 4, and then fell abruptly on day 6. In five subjects from group B, plasma TRP-6 was detectable in all plasma samples from day 10 to day 49. Testosterone levels were in the castrate range after day 24. Mean LH level decreased progressively from day 14 to day 56. These data provide evidence for the efficacy of periodic administration of TRP-6 microcapsules for suppressing testicular secretion.

Aged↗
PubMed1985

Pharmacokinetics of fenfluramine and norfenfluramine in volunteers given D- and DL-fenfluramine for 15 days.

The kinetics of accumulation and elimination of d- and l-fenfluramine (F) and norfenfluramine (NF) have been studied in 8 young healthy volunteers given daily doses of 60 mg of sugar-coated tablets of 20 mg dl-F hydrochloride (dl-F) t.i.d. and capsules of 15 mg d-F hydrochloride (d-F) b.i.d. for 15 days. Repeated doses of d-F plus l-F gave the same values for the parameters measured as did d-F administered alone. Steady-state concentrations of all compounds were achieved within 4-8 days. The predicted mean steady-state concentrations of d-F and elimination half-lives calculated from the results of a previous single dose study were similar to those measured at steady state in this study, confirming the lack of effect of the drug on hepatic microsomal enzymes and on kinetics after repeated dosing. d-NF concentrations were approximately half those of the parent drug and the half-life was almost twice as long. Steady state concentrations both of L-f and l-NF were consistently about 40-50% higher than of the d-isomers and there was a comparable in the half-life.

Adult↗
PubMed1984

[An analog of gonadoliberin in the treatment of prostatic carcinoma].

Twenty-five patients with prostatic carcinoma were involved in a Gehan's oriented phase II trial of D-Trp6-LH-RH in daily doses of 500 mcg for 7 days and 100 mcg for 3 months, this lapse of time being considered optimal for evaluation of the short-term response to treatment in this disease. Serum levels of LH and testosterone decreased rapidly. After 3 months of treatment, pain had disappeared in 14/21 patients; urinary symptoms had completely regressed in 10/22 patients and partially regressed in 9. A more than 50% reduction in prostatic enlargement was detected by ultrasonography in 7/19 patients, and the overall proportion of regression at scintigraphy was 43%. Prostatic acid phosphatases decreased by more than 50% in 10/15 patients. The results obtained with this LH-RH agonist were equivalent to those of orchidectomy and oestrogen therapy. The new drug was well tolerated. Although some of the patients treated are still responding after more than 15 months of treatment, further studies are required to evaluate the duration of response.

Adenocarcinoma↗
PubMed1984

An oriented phase-II trial of D-Trp6-LH-RH in patients with prostatic carcinoma.

An oriented phase II trial of D-Trp6-LH-RH was conducted according to Gehan's statistical method on 25 patients suffering from prostatic carcinoma. LH and testosterone serum levels decreased rapidly. Pain disappeared during the third month in 14 out of the 21 patients and markedly decreased in 5. Prostatism completely regressed in 10 out of the 22 subjects presenting it and markedly decreased in 9. Prostate hypertrophy regressed, as shown by ultrasonography, in 84% and by more than 50% in 37% of the patients. The overall regression rate of bone scintigraphy images was 43%; a regression of more than 50% was only registered in 12.5% of the patients; this may be explained by the long time which is necessary before bone image disappearance occurs. Prostatic acid phosphatase levels regressed in 75% and by more than 50% in 66.7% of the patients.

Acid Phosphatase↗
PubMed1984

[Treatment of prostatic cancer with an LH-RH agonist: the D Trp6 LH-RH. Preliminary results in 30 cases].

Thirty patients with advanced prostatic cancers (8 stage C, and 22 stage D) were treated for at least three months with D Trp6 LH-RH, a powerful LH-RH agonist. In all the cases in which the testosterone levels had been normal before treatment, the treatment led to a decline to the levels observed after castration. In seven cases, the drop was preceded by a rise in the first few days of treatment. Twenty two patients reacted favorably to the "medical castration" resulting from LH-RH agonists (11 improved and 11 remained stable). The improvements were mainly noted in patients who had not undergone previous treatment. Four deaths were registered in patients already at an advanced stage. Two of these patients presented with visceral metastases in circumstances such that a sudden deterioration due to the agonists cannot be excluded.

Aged↗