Isoniazid uptake and growth inhibition of Mycobacterium tuberculosis in relation to time and concentration of pulsed drug exposures.

@article{Beggs1969IsoniazidUA,
  title={Isoniazid uptake and growth inhibition of Mycobacterium tuberculosis in relation to time and concentration of pulsed drug exposures.},
  author={William H. Beggs and John W. Jenne},
  journal={Tubercle},
  year={1969},
  volume={50 4},
  pages={
          377-85
        }
}
Growth Inhibition of Mycobacterium tuberculosis After Single-Pulsed Exposures to Streptomycin, Ethambutol, and Rifampin
TLDR
It was reported earlier that the degree of growth inhibition of tubercle bacilli after single-pulsed isoniazid exposures is a function of the time-concentration product (TCP) of exposure rather than of either time or concentration alone, and studies have been extended to streptomycin, ethambutol (EMB), and rifampin (RMP).
Uptake and Binding of 14C-Ethambutol by Tubercle Bacilli and the Relation of Binding to Growth Inhibition
TLDR
It can be concluded that ethambutol enters the cells in a passive manner and definitive evidence showing identity in the concentrations of bound drug regardless of total uptake could explain the apparent discrepancy between concentration-dependent uptake and concentration-independent growth inhibition.
The early bactericidal activity of isoniazid related to its dose size in pulmonary tuberculosis.
Collections of sputum from 105 patients with newly diagnosed pulmonary tuberculosis were made before and at 1 and 2 d after the start of chemotherapy with isoniazid (INH) alone given to groups of
Cumulative effects of pulsed exposures of mycobacterium tuberculosis to isoniazid.
TLDR
The findings could be explained by the hypothesis of a primary effect of isoniazid, proportional to the time-concentration product, followed by secondary damage requiring time for its expression.
Pulsed-Exposure and Postantibiotic Leukocyte Enhancement Effects of Amikacin, Clarithromycin, Clofazimine, and Rifampin against Intracellular Mycobacterium avium
TLDR
Analysis of postantibiotic effects of four agents against Mycobacterium avium in a human macrophage model suggests that even a brief exposure of M. avium to peak concentrations of certain drugs in serum may result in prolonged and persistent suppression of bacterial growth inside human Macrophages.
Pharmacokinetic Contributions to Postantibiotic Effects
TLDR
Animal and human studies have reported that once-daily administration of aminoglycoside is as effective as, or more effective than, and possibly less toxic than traditional multiple daily administration.
The Postantibiotic Effect: A Review of in Vitro and in Vivo Data
TLDR
Animal studies reveal in vivo PAEs in accordance with PAEs obtained in vitro for most organism/ antimicrobial combinations, and the presence of a long PAE allowing aminoglycosides to be dosed infrequently suggests that beta-lactam antimicrobials require frequent or continuous dosing.
Postantibiotic effect in vitro
TLDR
The intention of this review is to present data contributed by the author on PAE in vitro, which will include: methods used for determination ofPAE, factors of importance for the presence and duration of PAE, the mechanism of action behind the PAe, and other postexposure events.
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References

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Isoniazid Uptake in Relation to Growth Inhibition of Mycobacterium tuberculosis
TLDR
The evidence obtained in this study suggests that the absolute concentration of bound INH is not as important in the action of the drug as is the maintenance of a critical cellular concentration for a requisite period of time.
Mechanism for the Pyridoxal Neutralization of Isoniazid Action on Mycobacterium tuberculosis
TLDR
It is postulated that a large excess of pyridoxal in Sauton's medium protects tubercle bacilli from the effects of isoniazid through formation of an extracellular complex involving drug, vitamin, and certain medium constituents, thereby reducing the level of isonianzid available to the cells.
BACTERICIDAL EFFECT OF ISONIAZID AS A FUNCTION OF TIME.
TLDR
In humans, a single daily dose of isoniazid that establishes an effective serum concentration for only a brief period of time seems to be therapeutically effective (8).
The uptake and fate of isoniazid in Mycobacterium tuberculosis var. bovis BCG.
  • J. Wimpenny
  • Chemistry, Medicine
    Journal of general microbiology
  • 1967
TLDR
Chromatographic studies on hot-water extracts of INH-treated BCG indicated that INH was converted into several unidentified products within the organism, suggesting that all these functions were part of one enzyme which was missing from INh-resistant BCG.
A review of the action of isoniazid.
  • J. Youatt
  • Biology, Medicine
    The American review of respiratory disease
  • 1969
TLDR
It is suggested that the primary and specific action of isoniazid is to combine with an enzyme that is peculiar to the drug-susceptible strains of Mycobacterium tuberculosis, at the same time displacing a molecule that gives rise to pigment in conditions in which the drug is not lethal.
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