Source: European Medicines Agency (EU) Revision Year: 2016 Publisher: Supplier: Micro Labs Limited, #27, Race Course Road, Bangalore 560 001, Karnataka, India, Tel: +91-80-2237 0451 to 2237 0457, Fax: +91-80-2237 0463, Email: jainethesh@microlabs.in
Protionamide is bacteriostatic against M. tuberculosis at therapeutic concentrations, but may be bactericidal at higher concentrations. Protionamide is also active against M. kansasii, M. leprae and some strains of M. avium-complex. The exact mechanism of action of protionamide has not been fully elucidated, but the drug appears to inhibit peptide synthesis in susceptible organisms. Protionamide is prodrug that needs activation by mycobacterial enzymes. Drug resistance develops rapidly when protionamide is given as monotherapy. Protionamide and ethionamide are completely cross-resistant.
Protionamide is nearly completely absorbed upon oral administration. Following single dose administration of Protionamide 250mg Tablets in healthy volunteers, the mean (± SD) protionamide Cmax value was 1729 ng/ml (± 768ng/ml), the corresponding value for AUC0-t was 5661 ng.h/ml (± 1679 ng.h/ml).The mean (± SD) protionamide tmax value was 1.20 (± 0.62) hours.
Protionamide is converted to active sulfoxide metabolites which then are metabolized to nicotinamide and nicotinic acid forms.
Plasma protein binding is approximately 30%, and the volume of distribution has been reported to be approximately 80 litres. Protionamide has good penetration into the cerebrospinal fluid. Protionamide undergoes extensive hepatic metabolism into several different metabolites, with only approximately 1% of a given dose excreted unchanged in the urine. Protionamide-sulfoxide is the major metabolite; it has been reported to have antibacterial activity. The plasma half-life of protionamide is approximately 2-3 hours.
Renal/hepatic impairment: Pharmacokinetic data are available neither for patients with renal impairment nor for patients with mild to moderate hepatic impairment (see section 4.2).
Data on the pharmacokinetics of protionamide in paediatric patients are scarce. One study in children aged 0-12 years showed that a daily dose of 15-20 mg/kg yielded Cmax values above a target concentration of 2.5µg/ml in the majority of patients. This target concentration was based on published expert opinion. Exposures tended to be lower in younger patients, particularly in those <2 years of age.
Non-clinical data reveal no special hazard for humans based on conventional studies of genotoxicity and carcinogenic potential.
Animal studies conducted with protionamide indicate that the drug had embryotoxic and teratogenic effects in mice, rabbits and rats. There were no studies on effects on male and female fertility.
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