Multiple-Dose Pharmacokinetics of Moxisylyte after Oral Administration to Healthy Volunteers

Costa, P.; Bressolle, F.; Jarroux, Elisabeth; Sarrazin, B.; Mosser, J.; Navratil, H; Galtier, M.

doi:10.1002/jps.2600820920

Cited by 6 publications

(2 citation statements)

References 13 publications

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“…To take into account the residual level of drug in plasma, the concentrations (C) in plasma at each sampling time were corrected as follows: [39][40][41][42] C corrected = C observed -C residual and C residual = C 0 exp -ke t ,…”

Section: Pharmacokinetic Analysis (Study 1)mentioning

confidence: 99%

Clozapine and Metabolite Concentrations during Treatment of Patients with Chronic Schizophrenia

Guitton¹,

Kinowski²,

Abbar

et al. 1999

The Journal of Clinical Pharma

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Results presented in this article are focused on the variability in pharmacokinetics. The purpose of this study was (1) to investigate intra- and interindividual variabilities of pharmacokinetic parameters of clozapine and its two main metabolites in plasma after multiple oral administration in 8 chronic schizophrenic patients (Study 1) and (2) to gain more information regarding plasma concentrations of these drugs after multiple doses in a group of 25 treatment-responsive patients (Study 2). Patients were treated with clozapine in fixed daily doses (given every 8-12 hours) between 200 and 900 mg. Plasma drug concentrations were determined by high-performance liquid chromatography. The mean volume of distribution and the total plasma clearance of clozapine, uncorrected for bioavailability, were 7 L/kg and 40.5 L/h, respectively. The terminal elimination half-lives averaged 10.5 hours for clozapine, 19.2 hours for norclozapine, and 8.6 hours for the N-oxide metabolite. Significant relationships were observed between clozapine and norclozapine (or clozapine N-oxide) plasma concentrations. Large inter- and intrapatient variations in pharmacokinetics were observed. Clozapine was generally well tolerated by the patients, with sedation, hypersialorrhea, and tiredness as the most common side effects encountered.

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Section: Pharmacokinetic Analysis (Study 1)mentioning

confidence: 99%

Clozapine and Metabolite Concentrations during Treatment of Patients with Chronic Schizophrenia

Guitton¹,

Kinowski²,

Abbar

et al. 1999

The Journal of Clinical Pharma

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show abstract

“…Moxisylyte (thymoxamine, 4-(2-dimethylamino-ethoxy)-5-isopropyl-2-methyl phenyl acetate), an ~-adrenoceptor predominate blocking agent [3], is the first drug with marketing authorisation in France for the treatment of impotence [4][5][6]. Its pharmacokinetics has been studied after IV [7][8][9], IC [8,10], and oral administration [7,11,12]. Moxisylyte can be considered as a prodrug, since rapid biotransformation occurs in blood.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses

Bressolle

Costa

Rouzier-Panis

et al. 1996

Eur J Clin Pharmacol

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Multiple-Dose Pharmacokinetics of Clozapine in Patients With Chronic Schizophrenia

Guitton¹,

Abbar²,

Kinowski³

et al. 1998

Journal of Clinical Psychopharmacology

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The pharmacokinetic parameters of clozapine and its two main metabolites, N-desmethylclozapine (norclozapine, active metabolite) and clozapine N-oxide, were evaluated, after oral administration, in 19 patients with chronic schizophrenia. Plasma and red blood cell (RBC) drug concentrations were determined by high-performance liquid chromatography. Large interpatient variations in pharmacokinetic parameters of clozapine and its two metabolites were observed. Plasma clozapine concentration peaked, on average, at 2.3 hours. The mean volume of distribution and the total plasma clearance, uncorrected for bioavailability, were 6 L/kg and 38 L/hr, respectively. The terminal elimination half-lives averaged 7.6 hours for clozapine, 13 hours for norclozapine, and 7 hours for the N-oxide metabolite. The mean RBC/plasma concentration ratios were 23, 61, and 81% for clozapine, N-desmethylclozapine, and clozapine N-oxide, respectively. From RBC concentration data, the mean elimination half-lives were 7.6 hours for clozapine, 16 hours for N-desmethylclozapine, and 8 hours for the N-oxide metabolite. The average value for blood clearance of clozapine was 54.7 L/hr. Significant correlations were observed between dose and maximum plasma concentrations and between dose and area under the curve concentrations; these results suggested linear steady-state pharmacokinetics over the range of concentrations studied.

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Multiple-Dose Pharmacokinetics of Moxisylyte after Oral Administration to Healthy Volunteers

Cited by 6 publications

References 13 publications

Clozapine and Metabolite Concentrations during Treatment of Patients with Chronic Schizophrenia

Clozapine and Metabolite Concentrations during Treatment of Patients with Chronic Schizophrenia

Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses

Multiple-Dose Pharmacokinetics of Clozapine in Patients With Chronic Schizophrenia

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