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Pyrazinamide is well absorbed from the Gl tract and attains peak plasma concentrations within 2 hours. Plasma concentrations generally range from 30 to 50 mcg/mL with doses of 20 to 25 mg/kg. It is widely distributed in body tissues and fluids including the liver, lungs and cerebrospinal fluid (CSF). The CSF concentration is approximately equal to concurrent steady-state plasma concentrations in patients with inflamed meninges.1 Pyrazinamide is approximately 10% bound to plasma proteins.2 The half-life (t 1/2) of pyrazi-namide is 9 to 10 hours in patients with normal renal and hepatic function. The plasma half-life may be prolonged in patients with impaired renal or hepatic function. Pyrazinamide is hydrolyzed in the liver to its major active metabolite, pyrazi-noic acid. Pyrazinoic acid is hydroxylated to the main excretory product, 5-hydrox-ypyrazinoic acid.3
Pyrazinamide may be bacteriostatic or bactericidal against Mycobacterium tuberculosis depending on the concentration of the drug attained at the site of infection. The mechanism of action is unknown. In vitro and in vivo the drug is active only at a slightly acidic pH.
1. Drug Information, American Hospital Formulary Service. American Society of Hospital Pharmacists. Bethesda, Md. 1991.
2. USPDI, Drug Information for the Health Care Professional. United States Pharmacopeial Convention, Inc. Rockville, Md. 1991: 1B: 2226-2227.
3. Goodman-Gilman A, Rall TW, Nies AS, Taylor P. The Pharmacological Basis of Therapeutics, ed 8. New York, Pergamon Press. 1990 ; 1154.
Last reviewed on RxList: 12/3/2008
This monograph has been modified to include the generic and brand name in many instances.
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