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P Costa - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetics of Moxisylyte in healthy volunteers after intravenous infusion and intracavernous administration with and without a penile tourniquet
Therapeutic Drug Monitoring, 1996Co-Authors: P Costa, H Navratil, Francoise Bressolle, R Rouzierpanis, N Mottet, C MarquerAbstract:The concentration-time profiles of metabolites of Moxisylyte (or thymoxamine), an alpha-blocking agent, were investigated in 18 healthy volunteers after intravenous (i.v.) and intracavernous (i.c.) administrations with and without a tourniquet. Four metabolites, unconjugated desacetylMoxisylyte (DAM), DAM glucuronide, and DAM and monodesmethylated DAM (MDAM) sulfates, were found in plasma and urine. For all metabolites, tmax was significantly increased after i.c. administrations and Cmax was significantly decreased. Maximum plasma level of unconjugated DAM was lower after i.c. administration with (1.81-fold) and without (1.26-fold) a tourniquet than after i.v. administration (43.6 +/- 19.6 ng/ml). The elimination half-life of each metabolite showed no change between the three treatments. The difference of 19 min between the mean residence times of unconjugated DAM after i.c. administration with and without a tourniquet may be compared with the difference between the mean duration of the intumescence, that is, 19 min (73 and 54 min with and without a tourniquet, respectively). Total percentages of metabolites recovered in urine were 66.2 +/- 20.9, 61.4 +/- 12.2, and 58.7 +/- 9.1% after i.v. and i.c. administrations with and without a tourniquet, respectively. In conclusion, tourniquet placed before i.c. administration increased the mean residence time of unconjugated DAM of approximately 25% and seemed to increase the efficacy of the drug in healthy volunteers.
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pharmacokinetics of Moxisylyte in healthy volunteers after intracavernous injection of increasing doses
European Journal of Clinical Pharmacology, 1996Co-Authors: F Bressolle, P Costa, R Rouzierpanis, C MarquerAbstract:Objective: The concentration-time profiles of specific metabolites of Moxisylyte, an α-adrenoceptor blocking agent, in the plasma and urine from 18 healthy volunteers were investigated after intracavernous (IC) administrations at three dose levels (10, 20 and 30 mg).
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efficacy and tolerance of intracavernous injection of Moxisylyte in patients with erectile dysfunction double blind placebo controlled study
Progres En Urologie, 1995Co-Authors: J Hermabessiere, P Costa, M C AndroAbstract:Buts : Evaluer l'efficacite du Moxisylyte intracaverneux comparativement a un placebo, chez des patients ayant un dysfonctionnement erectile d'origine variee. Apprecier la tolerance locale et generale du Moxisylyte administre par autoinjection. Methodes : Etude multicentrique, comportant deux phases de traitement : la premiere phase, conduite en double aveugle sur deux groupes paralleles de patients randomises, s'est deroulee sur une periode de 1 mois (1 injection par semaine) au cabinet de l'investigateur ; la deuxieme phase a ete conduite en ouvert au domicile du patient, sur une periode de 3 a 11 mois. Les autoinjections (1 a 2 par semaine) ont ete pratiquees a l'aide d'une seringue pre-remplie contenant 10 mg de Moxisylyte. Resultats : Sur les 307 patients evalues dans la premiere phase, la superiorite des reponses erectiles induites par le Moxisylyte par rapport au placebo a ete verifiee aux plans quantitatif et qualitatif (p<0,0001). La stabilite de la reponse au Moxisylyte a egalement ete confirmee sur les 4 injections, la frequence des reponses compatibles avec un rapport sexuel variant de 48% a 52% selon les injections. Cette efficacite a egalement ete maintenue durant la phase ouverte ou 92% des 4487 autoinjections ont genere des reponses erectiles positives. La qualite de ces reponses a ete jugee suffisante pour permettre un rapport sexuel apres 62% d'entre elles. La tolerance locale a ete jugee excellente pour plus de 95% des injections, sans effets indesirables majeurs avec un tres faible risque d'erection prolongee et de reaction fibrotique. La tolerance generale a egalement ete jugee excellente pour plus de 98% des injections. Conclusion : Cette etude confirme la possibilite d'obtenir une reponse erectile par injection intracaverneuse de 10 mg de Moxisylyte avec une tres faible incidence d'effets indesirables, au plan local et general. Elle tend egalement a verifier une efficacite plus importante du Moxisylyte lors d'autoinjections a domicile que par injection au cabinet medical.
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effectiveness of and tolerance to intracavernous injection of Moxisylyte in patients with erectile dysfunction effect dose relationship versus placebo
Progres En Urologie, 1995Co-Authors: H Navratil, P Costa, M C Andro, J F Louis, P SaurAbstract:Nous avons recherche la dose optimale (efficacite et tolerance) du Moxisylyte, un agent alpha-bloquant dans une etude croisee en double aveugle versus placebo incluant 30 patients. L'origine du dysfonctionnement erectile etait a predominance psychologique chez 14 patients et neurologique chez 16. Chaque patient a recu selon un ordre randomise, 4 injections intracaverneuses (placebo- 10 - 20 - 30 mg de Moxisylyte) separees par un delai de 7 jours. Quelle que soit la dose, le Moxisylyte induit des reponses peniennes significativement superieures au placebo sur tous les criteres de l'erection. La frequence des reponses permettant un rapport sexuel parait en relation avec les doses dans les deux groupes etiologiques. Les reponses erectiles les plus souvent obtenues ont ete une rigidite complete chez les «neurologiques» et une tumescence avec ou sans rigidite chez les «psychologiques». La tolerance a ete excellente pour 95,6% des injections et aucun priapisme n'a ete observe. Seuls 2 patients ont presente a 20 et 30 mg, l'un, deux erections prolongees (patient neurologique), l'autre, 2 cephalees (patient psychologique). Aucune sensation douloureuse a l'injection n'a ete ressentie. Tres bien tolere, le Moxisylyte permet d'induire une reponse erectile des la dose de 10 mg. Cette dose parait suffisante chez des patients dont le trouble est d'origine neurologique centrale ; une dose de 20 mg tend a ameliorer la qualite de la reponse chez les patients dont le trouble est a predominance psychologique, bien que les differences constatees entre les doses ne soient pas statistiquement significatives sur ce nombre limite de patients.
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changes in urethral pressure after intravenous injection of Moxisylyte hydrochloride in urethral instability in women preliminary results
Progres En Urologie, 1995Co-Authors: T Combes, A M Beguin, Y Coulomb, H Barouti, P CostaAbstract:But: Etudier l'action d'un alpha bloquant, le Chlorhydrate de Moxisylyte, lors d'un test intraveineux sur l'evolution des pressions uretrales chez des femmes presentant une instabilite uretrale associee a une hypertonie uretrale. Methodes: La population comprend 20 femmes d'âge moyen 38 ans, ayant un trouble mictionnel clinique (incontinence urinaire 15 fois, imperiosite 17 fois, pollakiurie 17 fois) evoluant en moyenne depuis 4 ans et presentant des variations de pressions uretrales au repos allant de 22 a 88 cmH 2 O (moyenne 44,8 cmH 2 O), les pressions uretrales statiques variant de 72 a 150 cmH 2 O) (moyenne 102,5 cmH 2 O). Un bilan urodynamique a ete pratique avant et apres injection intraveineuse de Chlorhydrate de Moxisylyte a la dose de 0,5 mg/kg de poids. Resuttats: On observe une baisse significative des variations de pressions uretrales, celles-ci variant de 8 a 42 cmH 2 O (moyenne 21,9 cmH 2 O), les pressions uretrales statiques variant de 47 a 102 cmH 2 O (moyenne 68,8 cmH 2 O). La tolerance clinique a ete bonne dans tous les cas. Conclusion: Ces premiers resultat devront etre completes par une etude randomisee contre placebo pour affirmer un effet statistiquement significatif du Chlorhydrate de Moxisylyte sur la stabilite des pressions uretrales chez des femmes presentant une instabilite uretrale
B Sarrazin - One of the best experts on this subject based on the ideXlab platform.
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multiple dose pharmacokinetics of Moxisylyte after oral administration to healthy volunteers
Journal of Pharmaceutical Sciences, 1993Co-Authors: P Costa, F Bressolle, Elisabeth Jarroux, B Sarrazin, Jacqueline Mosser, H Navratil, Marc GaltierAbstract:Abstract The pharmacokinetics of Moxisylyte in plasma and urine was investigated after oral administration. Twelve subjects were treated orally, twice daily with 240 mg of the drug for 6 days; on day 7, the subjects received a last dose of 240 mg of Moxisylyte. Moxisylyte was assayed in plasma and urine by a specific HPLC method with fluorimetric detection. Moxisylyte was absorbed rapidly and changed to its metabolites immediately after drug administration; unchanged Moxisylyte was not found in plasma. Two metabolites were found in plasma and urine: conjugated desacetylMoxisylyte (DAM) and the conjugate of desmeth- ylated DAM (MDAM). The pharmacokinetic parameters determined after the first oral administration were not modified on multiple dosing. The apparent elimination half-lives of conjugated DAM and MDAM were 2.3 and 3.5 h, respectively. Elimination of these two metabolites in urine averaged 50 and 10%, respectively.
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pharmacokinetics of Moxisylyte in healthy volunteers after intravenous and intracavernous administration
Journal of Pharmaceutical Sciences, 1993Co-Authors: P Costa, B Sarrazin, Jacqueline Mosser, Francoise Bressolle, Marc GaltierAbstract:The concentration-time profiles of metabolites of Moxisylyte, an alpha-adrenergic receptor blocking agent, in the plasma of 12 healthy volunteers were investigated after intravenous (iv) and intracavernous (ic) administrations. The study was conducted in open, randomized, Latin Squares. Plasma levels of Moxisylyte and its biotransformation products were assayed by a specific high-performance liquid chromatography method with fluorescence detection. Three metabolites, unconjugated desacetylMoxisylyte (DAM), conjugated DAM, and conjugated monodesmethylated DAM (MDAM), were found in plasma. After iv administration, unconjugated DAM appeared in plasma in < 5 min; the formation of this metabolite is slightly lower after ic administration (half-life, 6.08 +/- 2.33 min). Maximum plasma levels (57.2 +/- 29.4 ng/mL) and area under the curve of concentration versus time (43.3 +/- 11.4 micrograms.h/L) were significantly lower after ic administration than after iv administration (352.8 +/- 287.6 ng/mL and 152.6 +/- 0.247 micrograms.h/L, respectively). For conjugated DAM, the time to reach the maximum concentration is significantly increased after ic administration (0.9 h instead of 0.46 h) and the maximum concentration is significantly decreased (163.5 ng/mL instead of 203.4 ng/mL). The other pharmacokinetic parameters show no change between the two routes of administration. The pharmacokinetic parameters computed for MDAM are in the same range after iv and ic administrations, and there are no significant statistical differences.
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dose related effect of Moxisylyte on maximal urethral closing pressure in patients with spinal cord injuries
Clinical Pharmacology & Therapeutics, 1993Co-Authors: P Costa, B Sarrazin, Jacqueline Mosser, Francoise Bressolle, Robert SabatierAbstract:The effects of single intravenous doses of 0.25, 0.50, and 0.75 mg/kg Moxisylyte on maximum urethral closure pressure were evaluated in a placebo-controlled double-blind experiment in 20 patients with spinal cord injuries. Pharmacodynamic testing was performed until 30 minutes, and blood pressure was assessed until 60 minutes. Our findings showed a dose-dependent decrease in maximum urethral closure pressure. At each individual time point, the three doses differed significantly from placebo. Ten minutes after dose administration the maximum effect (48% decrease) was obtained with 0.75 mg/kg. A significant difference in favor of the highest dose was shown from 15 to 20 minutes after administration. According to these findings and because 0.75 mg/kg was as well tolerated as the two other doses, such a drop in pressure indicates that the α-blocking agent Moxisylyte may be an effective means of decreasing urethral resistance, with obvious implications for the management of urinary obstruction. Clinical Pharmacology and Therapeutics (1993) 53, 443–449; doi:10.1038/clpt.1993.49
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efficiency and side effects of intracavernous injections of Moxisylyte in impotent patients a dose finding study versus placebo
The Journal of Urology, 1993Co-Authors: P Costa, F Bressolle, B Sarrazin, M H Colson, Pierre Bondil, F SaudubrayAbstract:AbstractWe assessed the efficiency and tolerance of the «-blocking agent Moxisylyte in 2 double-blind studies versus placebo performed in 12 neurogenic patients with spinal cord lesions and in 61 patients presenting with either psychogenic impotence (30) or erectile dysfunction that was predominantly neither psychogenic, hormonal nor neurogenic (31). In each etiological group patients were randomized (according to latin square method) to receive 3 single doses (10, 20 and 30mg.) of Moxisylyte and a placebo. The erectile response was determined 5, 10, 15, 20 and 30 minutes after each injection. Whatever etiology of impotence and dosage tested, the erectile response induced by Moxisylyte was significantly higher than the placebo-induced response. No difference occurred among the 3 doses. In 93% of the patients Moxisylyte induced an erectile response, including tumescence in 6, partial rigidity in 16 and complete rigidity in 46. Thus, in 62 of 73 patients (85%) the drug allowed initiation of erection adequat...
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Moxisylyte plasma kinetics in humans after intracavernous administration
Biopharmaceutics & Drug Disposition, 1992Co-Authors: P Costa, B Sarrazin, Jacqueline Mosser, H Navratil, Francoise Bressolle, Marc GaltierAbstract:Obtaining and sustaining an erection are common problems for the male spinal cord injury patient. Intracavernous injection of vasoactive substances offers a new treatment option but it must be approached with caution in this population. In this work, the use of an alpha-adrenergic blocking agent, Moxisylyte, after intracavernous administration for complete paraplegic patients with erectile impotence is described. During this study, the pharmacokinetic profile of Moxisylyte has been defined. Unchanged Moxisylyte is not found in plasma, this drug is immediately metabolized after administration. Three metabolites were found in plasma: desacetylMoxisylyte (DAM), conjugated DAM, and conjugates of desmethylated DAM (MDAM). Maximum plasma levels of 72.3 ng ml-1, 301.4 ng ml-1, and 88.8 ng ml-1 are obtained 0.22 h, 0.9 h, and 2.08 h after drug administration for these three metabolites, respectively. The elimination half-lives are 0.89 h, 2.16 h, and 5.32 h and the MRT, 1.38 h, 3.23 h, and 8.45 h, respectively. No side-effects were noted, only one patient presented sleepiness. Successful erections (10 to 25 min) were obtained in all patients and no priapism was noted.
F Bressolle - One of the best experts on this subject based on the ideXlab platform.
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Moxisylyte a review of its pharmacodynamic and pharmacokinetic properties and its therapeutic use in impotence
Fundamental & Clinical Pharmacology, 1998Co-Authors: C Marquer, F BressolleAbstract:Summary— Moxisylyte is a competitive noradrenaline antagonist, acting preferentially on post-synaptic alpha-1 adrenoceptors. It was introduced more than thirty years ago for the treatment of cerebro-vascular disorders and shown more recently effective in the urological field due to its ability to modulate the urethral pressure. Renewal of interest in this drug has been observed in recent years since the demonstration of the possibilities of vasoactive drugs in evaluation and treatment of erectile dysfunctions. Moxisylyte is a prodrug, rapidly transformed into an active metabolite in plasma (DeacetylMoxisylyte or DAM). Elimination of the active metabolite occurs by N-demethylation, sulpho- and glucuroconjugation. The N-demethylated metabolite is sulphoconjugated only. Urine is the main route of excretion. The metabolites of Moxisylyte can be determined in biological fluids by various methods using high-performance liquid chromatography. Their pharmacokinetics is dependent on the route of administration. By the oral route, the concentrations of the active metabolite are low, and the glucuroconide of DAM predominates over the sulphates. After intravenous and intracavernous injection, the active metabolite is proportionally higher, the two sulphates are equivalent and in larger amounts than the glucuronide. In the treatment of impotence, intracavernous injection of Moxisylyte at 10, 20 or 30 mg can induce an erection adequate for intercourse in most of the patients. Compared to inducing agents such as papaverine and prostaglandin El, Moxisylyte must be considered as a facilitator of male erection, its interest lying in the low rate of adverse effects, either general or local.
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pharmacokinetics of Moxisylyte in healthy volunteers after intracavernous injection of increasing doses
European Journal of Clinical Pharmacology, 1996Co-Authors: F Bressolle, P Costa, R Rouzierpanis, C MarquerAbstract:Objective: The concentration-time profiles of specific metabolites of Moxisylyte, an α-adrenoceptor blocking agent, in the plasma and urine from 18 healthy volunteers were investigated after intracavernous (IC) administrations at three dose levels (10, 20 and 30 mg).
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multiple dose pharmacokinetics of Moxisylyte after oral administration to healthy volunteers
Journal of Pharmaceutical Sciences, 1993Co-Authors: P Costa, F Bressolle, Elisabeth Jarroux, B Sarrazin, Jacqueline Mosser, H Navratil, Marc GaltierAbstract:Abstract The pharmacokinetics of Moxisylyte in plasma and urine was investigated after oral administration. Twelve subjects were treated orally, twice daily with 240 mg of the drug for 6 days; on day 7, the subjects received a last dose of 240 mg of Moxisylyte. Moxisylyte was assayed in plasma and urine by a specific HPLC method with fluorimetric detection. Moxisylyte was absorbed rapidly and changed to its metabolites immediately after drug administration; unchanged Moxisylyte was not found in plasma. Two metabolites were found in plasma and urine: conjugated desacetylMoxisylyte (DAM) and the conjugate of desmeth- ylated DAM (MDAM). The pharmacokinetic parameters determined after the first oral administration were not modified on multiple dosing. The apparent elimination half-lives of conjugated DAM and MDAM were 2.3 and 3.5 h, respectively. Elimination of these two metabolites in urine averaged 50 and 10%, respectively.
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efficiency and side effects of intracavernous injections of Moxisylyte in impotent patients a dose finding study versus placebo
The Journal of Urology, 1993Co-Authors: P Costa, F Bressolle, B Sarrazin, M H Colson, Pierre Bondil, F SaudubrayAbstract:AbstractWe assessed the efficiency and tolerance of the «-blocking agent Moxisylyte in 2 double-blind studies versus placebo performed in 12 neurogenic patients with spinal cord lesions and in 61 patients presenting with either psychogenic impotence (30) or erectile dysfunction that was predominantly neither psychogenic, hormonal nor neurogenic (31). In each etiological group patients were randomized (according to latin square method) to receive 3 single doses (10, 20 and 30mg.) of Moxisylyte and a placebo. The erectile response was determined 5, 10, 15, 20 and 30 minutes after each injection. Whatever etiology of impotence and dosage tested, the erectile response induced by Moxisylyte was significantly higher than the placebo-induced response. No difference occurred among the 3 doses. In 93% of the patients Moxisylyte induced an erectile response, including tumescence in 6, partial rigidity in 16 and complete rigidity in 46. Thus, in 62 of 73 patients (85%) the drug allowed initiation of erection adequat...
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pharmacokinetics of Moxisylyte in healthy volunteers after intravenous and oral administration
Journal of Pharmaceutical Sciences, 1992Co-Authors: P Costa, F Bressolle, Jacqueline Mosser, M Brometpetit, B SarrazinAbstract:Abstract The concentration‐time profiles of metabolites of Moxisylyte, an alpha‐blocking agent, in the plasma and urine of 12 healthy volunteers were investigated after intravenous (iv) and oral (two formulations) administration. The study was conducted with an open, randomized Latin squares design. Plasma and urine levels of Moxisylyte and its biotransformation products were assayed by a specific HPLC method with fluorescence detection. Plasma levels declined in a monophasic or biphasic pattern depending on the subject. Two metabolites, conjugated desacetylMoxisylyte (DAM) and conjugated monodesmethylated DAM (MDAM), were found in plasma and urine. Unconjugated DAM was found in plasma only after iv administration. The apparent elimination half‐lives of unconjugated DAM, conjugated DAM, and MDAM were 0.86, 1.7, and 3 h, respectively. The total amounts of metabolites (expressed as the equivalent of DAM) excreted in the urine were 75% after iv administration and 68 and 69% after oral administration of the two formulations. Oral absorption appeared to be complete for the two treatments. There was no statistical difference between the two oral formulations studied.
Marc Galtier - One of the best experts on this subject based on the ideXlab platform.
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multiple dose pharmacokinetics of Moxisylyte after oral administration to healthy volunteers
Journal of Pharmaceutical Sciences, 1993Co-Authors: P Costa, F Bressolle, Elisabeth Jarroux, B Sarrazin, Jacqueline Mosser, H Navratil, Marc GaltierAbstract:Abstract The pharmacokinetics of Moxisylyte in plasma and urine was investigated after oral administration. Twelve subjects were treated orally, twice daily with 240 mg of the drug for 6 days; on day 7, the subjects received a last dose of 240 mg of Moxisylyte. Moxisylyte was assayed in plasma and urine by a specific HPLC method with fluorimetric detection. Moxisylyte was absorbed rapidly and changed to its metabolites immediately after drug administration; unchanged Moxisylyte was not found in plasma. Two metabolites were found in plasma and urine: conjugated desacetylMoxisylyte (DAM) and the conjugate of desmeth- ylated DAM (MDAM). The pharmacokinetic parameters determined after the first oral administration were not modified on multiple dosing. The apparent elimination half-lives of conjugated DAM and MDAM were 2.3 and 3.5 h, respectively. Elimination of these two metabolites in urine averaged 50 and 10%, respectively.
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pharmacokinetics of Moxisylyte in healthy volunteers after intravenous and intracavernous administration
Journal of Pharmaceutical Sciences, 1993Co-Authors: P Costa, B Sarrazin, Jacqueline Mosser, Francoise Bressolle, Marc GaltierAbstract:The concentration-time profiles of metabolites of Moxisylyte, an alpha-adrenergic receptor blocking agent, in the plasma of 12 healthy volunteers were investigated after intravenous (iv) and intracavernous (ic) administrations. The study was conducted in open, randomized, Latin Squares. Plasma levels of Moxisylyte and its biotransformation products were assayed by a specific high-performance liquid chromatography method with fluorescence detection. Three metabolites, unconjugated desacetylMoxisylyte (DAM), conjugated DAM, and conjugated monodesmethylated DAM (MDAM), were found in plasma. After iv administration, unconjugated DAM appeared in plasma in < 5 min; the formation of this metabolite is slightly lower after ic administration (half-life, 6.08 +/- 2.33 min). Maximum plasma levels (57.2 +/- 29.4 ng/mL) and area under the curve of concentration versus time (43.3 +/- 11.4 micrograms.h/L) were significantly lower after ic administration than after iv administration (352.8 +/- 287.6 ng/mL and 152.6 +/- 0.247 micrograms.h/L, respectively). For conjugated DAM, the time to reach the maximum concentration is significantly increased after ic administration (0.9 h instead of 0.46 h) and the maximum concentration is significantly decreased (163.5 ng/mL instead of 203.4 ng/mL). The other pharmacokinetic parameters show no change between the two routes of administration. The pharmacokinetic parameters computed for MDAM are in the same range after iv and ic administrations, and there are no significant statistical differences.
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Moxisylyte plasma kinetics in humans after intracavernous administration
Biopharmaceutics & Drug Disposition, 1992Co-Authors: P Costa, B Sarrazin, Jacqueline Mosser, H Navratil, Francoise Bressolle, Marc GaltierAbstract:Obtaining and sustaining an erection are common problems for the male spinal cord injury patient. Intracavernous injection of vasoactive substances offers a new treatment option but it must be approached with caution in this population. In this work, the use of an alpha-adrenergic blocking agent, Moxisylyte, after intracavernous administration for complete paraplegic patients with erectile impotence is described. During this study, the pharmacokinetic profile of Moxisylyte has been defined. Unchanged Moxisylyte is not found in plasma, this drug is immediately metabolized after administration. Three metabolites were found in plasma: desacetylMoxisylyte (DAM), conjugated DAM, and conjugates of desmethylated DAM (MDAM). Maximum plasma levels of 72.3 ng ml-1, 301.4 ng ml-1, and 88.8 ng ml-1 are obtained 0.22 h, 0.9 h, and 2.08 h after drug administration for these three metabolites, respectively. The elimination half-lives are 0.89 h, 2.16 h, and 5.32 h and the MRT, 1.38 h, 3.23 h, and 8.45 h, respectively. No side-effects were noted, only one patient presented sleepiness. Successful erections (10 to 25 min) were obtained in all patients and no priapism was noted.
H Navratil - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetics of Moxisylyte in healthy volunteers after intravenous infusion and intracavernous administration with and without a penile tourniquet
Therapeutic Drug Monitoring, 1996Co-Authors: P Costa, H Navratil, Francoise Bressolle, R Rouzierpanis, N Mottet, C MarquerAbstract:The concentration-time profiles of metabolites of Moxisylyte (or thymoxamine), an alpha-blocking agent, were investigated in 18 healthy volunteers after intravenous (i.v.) and intracavernous (i.c.) administrations with and without a tourniquet. Four metabolites, unconjugated desacetylMoxisylyte (DAM), DAM glucuronide, and DAM and monodesmethylated DAM (MDAM) sulfates, were found in plasma and urine. For all metabolites, tmax was significantly increased after i.c. administrations and Cmax was significantly decreased. Maximum plasma level of unconjugated DAM was lower after i.c. administration with (1.81-fold) and without (1.26-fold) a tourniquet than after i.v. administration (43.6 +/- 19.6 ng/ml). The elimination half-life of each metabolite showed no change between the three treatments. The difference of 19 min between the mean residence times of unconjugated DAM after i.c. administration with and without a tourniquet may be compared with the difference between the mean duration of the intumescence, that is, 19 min (73 and 54 min with and without a tourniquet, respectively). Total percentages of metabolites recovered in urine were 66.2 +/- 20.9, 61.4 +/- 12.2, and 58.7 +/- 9.1% after i.v. and i.c. administrations with and without a tourniquet, respectively. In conclusion, tourniquet placed before i.c. administration increased the mean residence time of unconjugated DAM of approximately 25% and seemed to increase the efficacy of the drug in healthy volunteers.
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effectiveness of and tolerance to intracavernous injection of Moxisylyte in patients with erectile dysfunction effect dose relationship versus placebo
Progres En Urologie, 1995Co-Authors: H Navratil, P Costa, M C Andro, J F Louis, P SaurAbstract:Nous avons recherche la dose optimale (efficacite et tolerance) du Moxisylyte, un agent alpha-bloquant dans une etude croisee en double aveugle versus placebo incluant 30 patients. L'origine du dysfonctionnement erectile etait a predominance psychologique chez 14 patients et neurologique chez 16. Chaque patient a recu selon un ordre randomise, 4 injections intracaverneuses (placebo- 10 - 20 - 30 mg de Moxisylyte) separees par un delai de 7 jours. Quelle que soit la dose, le Moxisylyte induit des reponses peniennes significativement superieures au placebo sur tous les criteres de l'erection. La frequence des reponses permettant un rapport sexuel parait en relation avec les doses dans les deux groupes etiologiques. Les reponses erectiles les plus souvent obtenues ont ete une rigidite complete chez les «neurologiques» et une tumescence avec ou sans rigidite chez les «psychologiques». La tolerance a ete excellente pour 95,6% des injections et aucun priapisme n'a ete observe. Seuls 2 patients ont presente a 20 et 30 mg, l'un, deux erections prolongees (patient neurologique), l'autre, 2 cephalees (patient psychologique). Aucune sensation douloureuse a l'injection n'a ete ressentie. Tres bien tolere, le Moxisylyte permet d'induire une reponse erectile des la dose de 10 mg. Cette dose parait suffisante chez des patients dont le trouble est d'origine neurologique centrale ; une dose de 20 mg tend a ameliorer la qualite de la reponse chez les patients dont le trouble est a predominance psychologique, bien que les differences constatees entre les doses ne soient pas statistiquement significatives sur ce nombre limite de patients.
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multiple dose pharmacokinetics of Moxisylyte after oral administration to healthy volunteers
Journal of Pharmaceutical Sciences, 1993Co-Authors: P Costa, F Bressolle, Elisabeth Jarroux, B Sarrazin, Jacqueline Mosser, H Navratil, Marc GaltierAbstract:Abstract The pharmacokinetics of Moxisylyte in plasma and urine was investigated after oral administration. Twelve subjects were treated orally, twice daily with 240 mg of the drug for 6 days; on day 7, the subjects received a last dose of 240 mg of Moxisylyte. Moxisylyte was assayed in plasma and urine by a specific HPLC method with fluorimetric detection. Moxisylyte was absorbed rapidly and changed to its metabolites immediately after drug administration; unchanged Moxisylyte was not found in plasma. Two metabolites were found in plasma and urine: conjugated desacetylMoxisylyte (DAM) and the conjugate of desmeth- ylated DAM (MDAM). The pharmacokinetic parameters determined after the first oral administration were not modified on multiple dosing. The apparent elimination half-lives of conjugated DAM and MDAM were 2.3 and 3.5 h, respectively. Elimination of these two metabolites in urine averaged 50 and 10%, respectively.
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Moxisylyte plasma kinetics in humans after intracavernous administration
Biopharmaceutics & Drug Disposition, 1992Co-Authors: P Costa, B Sarrazin, Jacqueline Mosser, H Navratil, Francoise Bressolle, Marc GaltierAbstract:Obtaining and sustaining an erection are common problems for the male spinal cord injury patient. Intracavernous injection of vasoactive substances offers a new treatment option but it must be approached with caution in this population. In this work, the use of an alpha-adrenergic blocking agent, Moxisylyte, after intracavernous administration for complete paraplegic patients with erectile impotence is described. During this study, the pharmacokinetic profile of Moxisylyte has been defined. Unchanged Moxisylyte is not found in plasma, this drug is immediately metabolized after administration. Three metabolites were found in plasma: desacetylMoxisylyte (DAM), conjugated DAM, and conjugates of desmethylated DAM (MDAM). Maximum plasma levels of 72.3 ng ml-1, 301.4 ng ml-1, and 88.8 ng ml-1 are obtained 0.22 h, 0.9 h, and 2.08 h after drug administration for these three metabolites, respectively. The elimination half-lives are 0.89 h, 2.16 h, and 5.32 h and the MRT, 1.38 h, 3.23 h, and 8.45 h, respectively. No side-effects were noted, only one patient presented sleepiness. Successful erections (10 to 25 min) were obtained in all patients and no priapism was noted.