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RX BIN: 015558RX PCN: HTGroup ID: DDN6600Card Holder ID: DDN6600
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2019 Price of Zinamide

$89.2690 tablets/500 mg
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Pyrazinamide volume of distribution

The pharmacokinetics of pyrazinamide (PZA) in cerebrospinal fluid (CSF) and plasma of 10 rabbits were studied after separate intravenous (i.v.) and oral (p.o.) administration, in a cross-over study. Concentrations of PZA in biological fluids were determined by high performance liquid chromatography (HPLC). After p.o. dose PZA was absorbed rapidly and peak plasma concentration was attained at 0.5 h post administration. After i.v. dose, the plasma PZA concentrations declined rapidly within 10 min and subsequently more slowly following a bi-exponential manner. No difference was observed in the area under plasma concentration-time curves indicating oral absorption was complete and no apparent first-pass metabolism occurred. The (mean +/- S.D.) elimination t1/2 after i.v. (1.04 +/- 0.18 h) was significantly shorter (P less than 0.0005) than that after oral (1.95 +/- 0.63 h) dose and the apparent volume of distribution was also significantly smaller (P less than 0.005) after i.v. (3.211 +/- 0.412 l) than after oral (5.936 +/- 1.607 l) administration. The elimination t1/2 of PZA in CSF was nearly identical to that in plasma after either i.v. (1.07 +/- 0.20 h) or p.o. (1.84 +/- 0.56 h) administration. There is no apparent barrier in rabbits for the penetration of PZA into CSF from the general circulation.

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What is Pyrazinamide

A pyrazine that is used therapeutically as an antitubercular agent.

Pyrazinamide mechanism of action

Pyrazinamide diffuses into M. tuberculosis, where the enzyme pyrazinamidase converts pyrazinamide to the active form pyrazinoic acid. Under acidic conditions, the pyrazinoic acid that slowly leaks out converts to the protonated conjugate acid, which is thought to diffuse easily back into the bacilli and accumulate. The net effect is that more pyrazinoic acid accumulates inside the bacillus at acid pH than at neutral pH. Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids. However, this theory was thought to have been discounted (PMID: 11914348). However, further studies reproduced the results of FAS I inhibition as the putative mechanism first in whole cell assay of replicating M. tuberculosis bacilli which have shown that pyrazinoic acid and its ester inhibit the synthesis of fatty acids (PMID: 17101678). This study was followed by in vitro assay of tuberculous FAS I enzyme that tested the activity with pyrazinamide, pyrazinoic acid and several classes of pyrazinamide analogs. Pyrazinamide and its analogs inhibited the activity of purified FAS I (PMID: 17485499). It has also been suggested that the accumulation of pyrazinoic acid disrupts membrane potential and interferes with energy production, necessary for survival of M. tuberculosis at an acidic site of infection. Pyrazinoic acid has also been shown to bind to the ribosomal protein S1 (RpsA) and inhibit trans-translation. This may explain the ability of the drug to kill dormant mycobacteria (PMID: 21835980).

Dosage forms of Pyrazinamide

FormRouteStrength
Tabletoral500 mg/1
Tabletoral
Tablet, sugar coatedoral

Prescription Generics

false

International Brands

Pdp-pyrazinamide

Synonyms

2-carbamylpyrazine 2-pyrazinecarboxamide

Manufacturers

Pendopharm Division Of De Pharmascience Inc

CAS number

98-96-4

UNII

2KNI5N06TI

State

solid

Affected organisms

Mycobacterium tuberculosis

Indication of Pyrazinamide

For the initial treatment of active tuberculosis in adults and children when combined with other antituberculous agents.

Toxicity of Pyrazinamide

Side effects include liver injury, arthralgias, anorexia, nausea and vomiting, dysuria,malaise and fever, sideroblastic anemia, adverse effects on the blood clotting mechanism or vascular integrity, and hypersensitivity reactions such as urticaria, pruritis and skin rashes.

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