Ethionamide clinical pharmacology: Difference between revisions
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==Clinical Pharmacology== | |||
===Absorption=== | |||
Ethionamide is essentially completely absorbed following oral administration and is not subjected to any appreciable first pass metabolism. Ethionamide tablets may be administered without regard to the timing of meals. | |||
The pharmacokinetic parameters of ethionamide following single oral-dose administration of 250 mg of Trecator film-coated tablets under fasted conditions to 40 healthy adult volunteers are provided in Table 1. | |||
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Trecator tablets have been reformulated from a sugar-coated tablet to a film-coated tablet. The Cmax for the film-coated tablets (2.16 μg/mL) was significantly higher than that of sugar-coated tablets (1.48 μg/mL) (see DOSAGE AND ADMINISTRATION). | |||
===Distribution=== | |||
Ethionamide is rapidly and widely distributed into body tissues and fluids following administration of a sugar-coated tablet, with concentrations in plasma and various organs being approximately equal. Significant concentrations are also present in cerebrospinal fluid following administration of a sugar-coated tablet. Distribution of ethionamide into the same body tissues and fluids, including cerebrospinal fluid following administration of the film-coated tablet, has not been studied, but is not expected to differ significantly from that of the sugar-coated tablet. The drug is approximately 30% bound to proteins. The mean (SD) apparent oral volume of distribution observed in 40 healthy volunteers following a 250 mg oral dose of film-coated tablets was 93.5 (19.2) L. | |||
===Metabolism=== | |||
Ethionamide is extensively metabolized to active and inactive metabolites. Metabolism is presumed to occur in the liver and thus far 6 metabolites have been isolated: 2-ethylisonicotinamide, carbonyl-dihydropyridine, thiocarbonyl-dihydropyridine, S-oxocarbamoyl dihydropyridine, 2-ethylthioiso-nicotinamide, and ethionamide sulphoxide. The sulphoxide metabolite has been demonstrated to have antimicrobial activity against Mycobacterium tuberculosis. | |||
===Elimination=== | |||
The mean (SD) half-life observed in 40 healthy volunteers following a 250 mg oral dose of film-coated tablets was 1.92 (0.27) hours. Less than 1% of the oral dose is excreted as ethionamide in urine. | |||
===Mechanism of Action=== | |||
Ethionamide may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. The exact mechanism of action of ethionamide has not been fully elucidated, but the drug appears to inhibit peptide synthesis in susceptible organisms. | |||
Revision as of 14:53, 27 December 2013
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
Clinical Pharmacology
Absorption
Ethionamide is essentially completely absorbed following oral administration and is not subjected to any appreciable first pass metabolism. Ethionamide tablets may be administered without regard to the timing of meals.
The pharmacokinetic parameters of ethionamide following single oral-dose administration of 250 mg of Trecator film-coated tablets under fasted conditions to 40 healthy adult volunteers are provided in Table 1.
 |
Trecator tablets have been reformulated from a sugar-coated tablet to a film-coated tablet. The Cmax for the film-coated tablets (2.16 μg/mL) was significantly higher than that of sugar-coated tablets (1.48 μg/mL) (see DOSAGE AND ADMINISTRATION).
Distribution
Ethionamide is rapidly and widely distributed into body tissues and fluids following administration of a sugar-coated tablet, with concentrations in plasma and various organs being approximately equal. Significant concentrations are also present in cerebrospinal fluid following administration of a sugar-coated tablet. Distribution of ethionamide into the same body tissues and fluids, including cerebrospinal fluid following administration of the film-coated tablet, has not been studied, but is not expected to differ significantly from that of the sugar-coated tablet. The drug is approximately 30% bound to proteins. The mean (SD) apparent oral volume of distribution observed in 40 healthy volunteers following a 250 mg oral dose of film-coated tablets was 93.5 (19.2) L.
Metabolism
Ethionamide is extensively metabolized to active and inactive metabolites. Metabolism is presumed to occur in the liver and thus far 6 metabolites have been isolated: 2-ethylisonicotinamide, carbonyl-dihydropyridine, thiocarbonyl-dihydropyridine, S-oxocarbamoyl dihydropyridine, 2-ethylthioiso-nicotinamide, and ethionamide sulphoxide. The sulphoxide metabolite has been demonstrated to have antimicrobial activity against Mycobacterium tuberculosis.
Elimination
The mean (SD) half-life observed in 40 healthy volunteers following a 250 mg oral dose of film-coated tablets was 1.92 (0.27) hours. Less than 1% of the oral dose is excreted as ethionamide in urine.
Mechanism of Action
Ethionamide may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. The exact mechanism of action of ethionamide has not been fully elucidated, but the drug appears to inhibit peptide synthesis in susceptible organisms.
References
- ↑ "TRECATOR (ETHIONAMIDE) TABLET, FILM COATED [WYETH PHARMACEUTICALS COMPANY, A SUBSIDIARY OF PFIZER INC.]". Text " accessdate " ignored (help)
Adapted from the FDA Package Insert.