Pyrazinamide and Other Drugs in Tuberculous Meningitis

Forgan-Smith, Ross; Ellard, G. A.; Newton, Duncan; Mitchison, D. A.

doi:10.1016/s0140-6736(73)93211-x

Cited by 40 publications

(18 citation statements)

References 11 publications

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“…This result is consistent with CSF analysis in humans in which the PZA concentration in the CSF exceeded that in the serum 29. For example, in the brain the C 60min was 0.00463 %ID/cc while in the plasma the C 60min was 0.00272 %ID/cc.…”

Section: Resultssupporting

confidence: 88%

Radiosynthesis and Bioimaging of the Tuberculosis Chemotherapeutics Isoniazid, Rifampicin and Pyrazinamide in Baboons

Liu

Xu²,

Shea³

et al. 2010

J. Med. Chem.

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The front-line tuberculosis (TB) chemotherapeutics isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) have been labeled with carbon-11 and the biodistribution of each labeled drug has been determined in baboons using positron emission tomography (PET). Each radiosynthesis and formulation has been accomplished in 1 h, using [11C]CH3I to label RIF, and [11C]HCN to label INH and PZA. Following i.v. administration, INH, PZA, RIF and/or their radiolabeled metabolites clear rapidly from many tissues, however INH, PZA and/or their metabolites accumulate in the bladder while RIF and/or its metabolites accumulates in the liver and gall bladder, consistent with the routes of excretion of the drugs. In addition, the biodistribution data demonstrate that the ability of the three drugs and their radiolabeled metabolites to cross the blood-brain barrier decreases in the order PZA > INH > RIF, although in all cases the estimated drug concentrations are greater than the minimum inhibitory concentration (MIC) values for inhibiting bacterial growth. The pharmacokinetic (PK) and drug distribution data have important implications for treatment of disseminated TB in the brain, and pave the way for imaging the distribution of the pathogen in vivo.

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Section: Resultssupporting

confidence: 88%

Radiosynthesis and Bioimaging of the Tuberculosis Chemotherapeutics Isoniazid, Rifampicin and Pyrazinamide in Baboons

Liu

Xu²,

Shea³

et al. 2010

J. Med. Chem.

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“…The excellent penetration of pyrazinamide into the cerebrospinal fluid (CSF) was first demonstrated in a single case report of a patient with tuberculous meningitis. 3 This finding was confirmed in recent studies in a larger number of patients with tuberculous meningitis.' A number of antituberculosis drugs, notably ethambutol, rifampicin and streptomycin, pass into the CSF in sufficient concentrations during the active stage of tuberculous meningitis but, after treatment, as the blood-brain barrier is restored, the concentrations of these drugs in the CSF decrease.7 Data on the penetration of pyrazinamide into the CSF during the course of treatment of the meningitis are limited.…”

supporting

confidence: 62%

The blood/cerebrospinal fluid partitioning of pyrazinamide: a study during the course of treatment of tuberculous meningitis.

Phuapradit

Supmonchai

Kaojarern

et al. 1990

Journal of Neurology, Neurosurgery & Psychiatry

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“…Experiments demonstrating that RMP was more effective than other antimicrobial agents in killing Staphylococcus aureus within polymorphonuclear leukocytes have been explained by assuming that RMP penetrates the cell more effectively (38). This explanation cannot account for differences between INH and RMP in vivo, because INH has been shown to be highly effective against intracellular tubercle bacilli (3) and penetrates the blood-brain (39) and other membrane barriers with ease (40). Inactivity of SM on organisms in cells (3,41) may, however, account for its failure as a sterilizing drug.…”

Section: Discussionmentioning

confidence: 99%

Bactericidal Activity of Streptomycin, Isoniazid, Rifampin, Ethambutol, and Pyrazinamide Alone and In Combination Against Mycobacterium Tuberculosis¹

Dickinson¹,

Aber²,

Mitchison³

1977

Am Rev Respir Dis

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Log-phase cultures of Mycobacterium tuberculosis in Tween-albumin medium were exposed to streptomycin, isoniazid, rifampin, ethambutol, and pyrazinamide in concentrations in the range likely to be present in serum during treatment of patients. The bactericidal activity of the drugs was measured as the decrease in viable counts at 4 and 7 days. The activity of single drugs was highest for streptomycin and next highest for rifampin and isoniazid, but ethambutol only started to kill after 4 days. When exposed to 2 drugs, bactericidal synergism was found with streptomycin/isoniazid and isoniazid/ethambutol; additivity, with streptomycin/rifampin; indifference, with isoniazid rifampin and streptomycin/ethambutol; and antagonism, with rifampin/ethambutol and isoniazid/pyrazinamide. When cultures were exposed to the 3 drugs, isoniazid, rifampin, and ethambutol, marked antagonism was found between isoniazid and rifampin, whereas the addition of isoniazid or an increase in its concentration increased the bactericidal activity.

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Pyrazinamide and Other Drugs in Tuberculous Meningitis

Cited by 40 publications

References 11 publications

Radiosynthesis and Bioimaging of the Tuberculosis Chemotherapeutics Isoniazid, Rifampicin and Pyrazinamide in Baboons

Radiosynthesis and Bioimaging of the Tuberculosis Chemotherapeutics Isoniazid, Rifampicin and Pyrazinamide in Baboons

The blood/cerebrospinal fluid partitioning of pyrazinamide: a study during the course of treatment of tuberculous meningitis.

Bactericidal Activity of Streptomycin, Isoniazid, Rifampin, Ethambutol, and Pyrazinamide Alone and In Combination Against Mycobacterium Tuberculosis¹

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Pyrazinamide and Other Drugs in Tuberculous Meningitis

Cited by 40 publications

References 11 publications

Radiosynthesis and Bioimaging of the Tuberculosis Chemotherapeutics Isoniazid, Rifampicin and Pyrazinamide in Baboons

Radiosynthesis and Bioimaging of the Tuberculosis Chemotherapeutics Isoniazid, Rifampicin and Pyrazinamide in Baboons

The blood/cerebrospinal fluid partitioning of pyrazinamide: a study during the course of treatment of tuberculous meningitis.

Bactericidal Activity of Streptomycin, Isoniazid, Rifampin, Ethambutol, and Pyrazinamide Alone and In Combination Against Mycobacterium Tuberculosis1

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Bactericidal Activity of Streptomycin, Isoniazid, Rifampin, Ethambutol, and Pyrazinamide Alone and In Combination Against Mycobacterium Tuberculosis¹