2- Pyrazinoic acid

In many other cases, hydrolysis results in drug inactivation, as with the tuberculostatic agent pyrazinamide (4.69). In humans and rats, the metabolism of this compound involves deamidation to produce pyrazinoic acid (4.70). Ring oxidation is another major pathway, leading to 5-hydroxypyrazinamide (4.71), which, in turn, is hydrolyzed to 5-hydroxypyrazinoic acid (4.72). The rates of hydrolysis were found to determine the apparent half-life of pyrazinamide [42] [43]. 

It is chemically related to nicotinamide and thiosemicarbazone. It is bactericidal. It is effective against Mycobacterium tuberculosis resistant to INH and streptomycin. It is converted to pyrazinoic acid (active... 

Pyrazinamide is converted to pyrazinoic acid—the active form of the drug—by mycobacterial pyrazinamidase, which is encoded by pncA. The drug target and mechanism of action are unknown. Resistance may be due to impaired uptake of pyrazinamide or mutations in pncA that impair conversion of pyrazinamide to its active form. 

Ar-(2-Pyrazinoyl)morpholine (67) and its 6-chloro (68) and 6-methoxy derivatives (69) are useful antidiabetic drugs.238-240 Compound 67 is prepared from pyrazinoyl chloride and morpholine,241 or alternatively by reaction of pyrazinoic acid with ethyl chloro-... 

Pyrazinealdehyde undergoes the normal reactions of aromatic aldehydes. Thus, the Cannizzaro reaction gives the expected products, pyrazylmethanol and pyrazinoic acid, and reaction with aqueous potassium cyanide gives l,2-dipyrazylethene-l,2-diol (71) in 85% yield.243... 

Pyrantel embonate, 947 Pyrantel pamoate, 947 Pyrantel tartrate, 947 Pyrazinamide, 947 Pyrazinecarboxamide, 947 Pyrazinecarboxylic acid, 947 Pyrazinoic acid amide, 947 Pyrazolopyrimidinol, 327 Pyrazolylethylamine, 335 Pyrethrin I, 77, 85 Pyrethrin II, 77, 85 Pyrethrolone, 77 Pyribenzamine, 1052 Pyridacil, 873... 

SYNS ALDINAiMID 2-CARBAMYL PYRAZINE D-50 F.PRA7.TN MK 56 NCI-C01785 PYRAZINAMIDE PYRAZINEAMIDE PYRAZINE CARBOXYLAMIDE PYRAZINOIC ACID AMIDE TEBRAZID... 

Pyrazinamide is a derivative of nicotinamide and is included in first-choice combination regimens because of its particular ability to kill intracellular persisters, i.e. mycobacteria that are dividing or semidormant, often within cells. Its action is dependent on the activity of intrabacterial pyrazinami-dase which converts pyrazinamide to the active pyrazinoic acid this eirzyme is most effective in an acidic environment such as the interior of cells. It is inactive against Mycobacterium bovis. Pyrazinamide is well absorbed from the gastrointestinal tract and metabolised in the liver, very little imchanged drug... 

Adverse effects include hyperuricaemia and arthralgia, which is relatively frequent with daily but less so with intermittent dosing and, unlike gout, affects both large and small joints. Pyrazinoic acid, the principal metabolite of pyrazinamide, inhibits renal tubular secretion of urate. Symptomatic treatment with an NSAID is usually sufficient and it is rarely necessary to discontinue pyrazinamide because of arthralgia. Hepatitis, which was particularly associated with high doses, is not a problem with modern short-course schedules. Sideroblastic anaemia and urticaria also occur. 

The process by which the kidney accumulates cisplatin is oxygen-dependent [10] and is competitively inhibited by drugs that are transported by the organic base system. Conversely, drugs that compete for the organic anion transport system, such as PAH and pyrazinoic acid, do not inhibit cisplatin uptake. Collectively, these observations indicate that the renal uptake of cisplatin involves transport or binding to components of the base transport system. 

Pyrazinamide is well absorbed from the GI tract and widely distributed throughout the body, including the CNS, lungs, and liver. The plasma t is 9-10 hours in patients with normal renal function. The drug is excreted primarily by glomerular filtration. Pyrazinamide is hydrolyzed to pyrazinoic acid and subsequently hydroxylated to 5-hydroxypyrazinoic acid. 

PharmacoWnetics Pyrazinamide is well absorbed orally and penetrates most body tissues, including the CNS. The drug is partly metabolized to pyrazinoic acid, and both parent molecule and metabolite are excreted in the urine. The plasma half-life of pyrazinamide is increased in hepatic or renal failure. 

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