Relative Bioavailability of Four Clomipramine Hydrochloride Tablet Products

Müller, F. O.; Schall, Robert; Mogilnicka, E; Groenewoud, G.; Hundt, H. K. L.; Luus, H. G.; Middle, M. V.; Swart, K.J; Vaal, A. C. De

doi:10.1002/(sici)1099-081x(199601)17:1<81::aid-bdd939>3.0.co;2-5

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“…Since determination of the pharmacokinetic parameters of R-deprenyl was difficult because of its low plasma concentration due to considerable first pass metabolism and rapid tissue distribution, in early bioequivalence studies plasma concentrations of the main desalkylated metabolites, MA and desmethyldeprenyl (DD) instead of the parent compound were compared in case of the various preparations [57,60]. In 1994 Mahmood et al [55] have developed a sensitive fluorimetric method for determination of R-deprenyl concentration in plasma.…”

Section: Pharmacokinetic Characteristics Of R-deprenylsupporting

confidence: 79%

R-Deprenyl: Pharmacological Spectrum of its Activity

et al. 2010

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Deprenyl has been discovered by Knoll and co-workers. The R-enantiomer of deprenyl (selegiline) is a selective and irreversible inhibitor of the B-isoform of monoamine oxidase (MAO-B) enzyme. Due to its dopamine potentiating and possible neuroprotective properties it has an established role in the treatment of parkinsonian patients. By inhibiting MAO-B enzyme, R-deprenyl decreases the formation of hydrogen peroxide, alleviating the oxidative stress also reduced by increased expression of antioxidant enzymes (superoxide dismutases and catalase) reported during chronic treatment. It was shown to prevent the detrimental effects of neurotoxins like MPTP and DSP-4. R-Deprenyl elicits neuroprotective and neuronal rescue activities in concentrations too low to inhibit MAO-B. It is extensively metabolized and some of the metabolites possess pharmacological activities, thus their contribution to neuroprotective properties was also suggested. The recently identified deprenyl-N-oxide is extensively studied in our laboratory. Effects other than neuroprotection, like influencing cell adhesion and proliferation cannot be neglected.

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Section: Pharmacokinetic Characteristics Of R-deprenylsupporting

confidence: 79%

R-Deprenyl: Pharmacological Spectrum of its Activity

et al. 2010

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Increased bioavailability of clomipramine after sublingual administration in rats

Yoo

Yoon

Lee

et al. 1999

Journal of Pharmaceutical Sciences

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This study examined the absorption and disposition of clomipramine in rats after sublingual (5 and 50 mg/kg), oral (50 mg/kg), and iv (5 mg/kg) administration. The mean oral bioavailability of clomipramine was 24.8% and 29.7%, respectively, in conscious rats and in rats anesthetized with ketamine/xylazine (30/3 mg/kg). When given sublingually in isotonic saline at a dose of 50 mg/kg, clomipramine was rapidly absorbed, and the mean absolute bioavailability (36.2%) was increased over oral dosing. The mean AUC values of clomipramine were 2258 +/- 1762 ng.h/mL and 1891 +/- 867 ng.h/mL after oral administration to conscious and anesthetized rats, respectively, and 3303 +/- 1576 ng.h/mL after sublingual administration to anesthetized rats. Sublingual administration (5 mg/kg doses) of clomipramine formulated with a permeation enhancer, 2-hydroxypropyl beta-cyclodextrin, further increased the sublingual bioavailability to 57.1%. The sublingual route may be an alternative route of administration of clomipramine, providing enhanced bioavailability.

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Pharmacokinetics of a Sustained‐Release Dosage Form of Clomipramine

Herrera

Mayet

Galindo

et al. 2000

The Journal of Clinical Pharma

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In this study, the pharmacokinetic parameters of the sustained‐release (SR) dosage form of clomipramine (CMI) were compared with those obtained after the administration of the immediate‐ release (IR) dosage form. Two studies were performed. In the first study, a single oral dose of both products was administered in 12 healthy volunteers, and in the second study, multiple doses of both products were administered in 6 patients with depression in which steady‐state plasma levels (Css) were determined. Plasma levels were assayed using an HPLC method. In the single‐dose study, the mean Cmax and AUC values of CMI were 63.37 ng/mL−1 and 1375.38 ng•h/mL−1 for the reference product and 32.55 ng/mL−1 and 1285.26 ng•h/mL−1 for the test product, respectively. The mean β and MRT values of CMI were 0.030 h−1 and 47.21 h for the reference product and 0.026 h−1 and 55.63 h for test product, respectively. Results showed that after the multiple‐dose study, the mean clomipramine plus demethylclomipramine values of Cssav were 406.2 ng/mL−1 for the reference and 328.6 ng/mL−1 for the sustained‐release dosage form. This product also presented less fluctuation in steady‐state plasma levels (1.08 vs. 1.23). The values of MRT and tmax were higher for the SR dosage form, showing that the drug was maintained longer in the body. The mean values for the ratio metabolite/drug were 2.06 and 2.41 for the IR and SR dosage forms, respectively. Neither AUC nor elimination half‐life was affected significantly after the administration of the sustained‐release dosage form.

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Relative Bioavailability of Four Clomipramine Hydrochloride Tablet Products

Cited by 3 publications

References 1 publication

R-Deprenyl: Pharmacological Spectrum of its Activity

R-Deprenyl: Pharmacological Spectrum of its Activity

Increased bioavailability of clomipramine after sublingual administration in rats

Pharmacokinetics of a Sustained‐Release Dosage Form of Clomipramine

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