Activities of pefloxacin and ofloxacin against mycobacteria: in vitro and mouse experiments

C. Truffot-Pernot, B. Ji, J. Grosset

Research output: Contribution to journalArticle

Abstract

The minimal inhibitory concentrations for 90% of strains (MIC90) of ofloxacin against Mycobacterium tuberculosis and Mycobacterium xenopi was 2 mg/I. This was three dilutions lower than that of pefloxacin and was well within the range of drug concentrations achievable in man. The antituberculosis activities of both quinolones were independent of resistance of the strains to other antimycobacteriaI agents. Mycobacterium avium-intracellulare was resistant to both compounds with MIC90s greater than 16 mg/l. The maximum serum levels (Cmax) of both compounds increased proportionally with increasing dose size. The terminal elimination half-life (T 1 2) of pefloxacin was longer than that of ofloxacin, but the T 1 2 of both compounds in mice were much shorter than in man. The area under the concentration curve (AUC) of pefloxacin was double than that of ofloxacin. In the mouse, pefloxacin at doses up to 150 mg/kg daily was inactive against M. tuberculosis infection: in terms of survival rate the minimal effective dose of ofloxacin against M. tuberculosis infection was 150 mg/kg daily when given by gavage or by incorporation into the mouse diet at a concentration of 0.1 %, but in terms of cfu counts, ofloxacin 150 mg/kg daily only displayed a moderate degree of activity similar to ethambutol 100 mg/kg daily. The therapeutic effects of ofloxacin against M. tuberculosis infection were dose-related: 300 mg/kg daily by gavage or 0.4% in mouse diet displayed much better therapeutic effects than lower dosages. Since the AUC in mice treated with ofloxacin 150 mg/kg daily is close to that in man treated with a clinically tolerated dose-600 mg daily-such a dosage may be only moderately effective against human tuberculosis.

Original languageEnglish (US)
Pages (from-to)57-64
Number of pages8
JournalTubercle
Volume72
Issue number1
DOIs
StatePublished - 1991
Externally publishedYes

Fingerprint

Pefloxacin
Ofloxacin
Mycobacterium
Mycobacterium tuberculosis
Mycobacterium Infections
Therapeutic Uses
Area Under Curve
Mycobacterium xenopi
Diet
Mycobacterium avium Complex
Ethambutol
Quinolones
In Vitro Techniques
Half-Life
Tuberculosis
Survival Rate
Serum

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Activities of pefloxacin and ofloxacin against mycobacteria : in vitro and mouse experiments. / Truffot-Pernot, C.; Ji, B.; Grosset, J.

In: Tubercle, Vol. 72, No. 1, 1991, p. 57-64.

Research output: Contribution to journalArticle

Truffot-Pernot, C. ; Ji, B. ; Grosset, J. / Activities of pefloxacin and ofloxacin against mycobacteria : in vitro and mouse experiments. In: Tubercle. 1991 ; Vol. 72, No. 1. pp. 57-64.
@article{8b8c6fd0227549eebbd8b4f18549b6b6,
title = "Activities of pefloxacin and ofloxacin against mycobacteria: in vitro and mouse experiments",
abstract = "The minimal inhibitory concentrations for 90{\%} of strains (MIC90) of ofloxacin against Mycobacterium tuberculosis and Mycobacterium xenopi was 2 mg/I. This was three dilutions lower than that of pefloxacin and was well within the range of drug concentrations achievable in man. The antituberculosis activities of both quinolones were independent of resistance of the strains to other antimycobacteriaI agents. Mycobacterium avium-intracellulare was resistant to both compounds with MIC90s greater than 16 mg/l. The maximum serum levels (Cmax) of both compounds increased proportionally with increasing dose size. The terminal elimination half-life (T 1 2) of pefloxacin was longer than that of ofloxacin, but the T 1 2 of both compounds in mice were much shorter than in man. The area under the concentration curve (AUC) of pefloxacin was double than that of ofloxacin. In the mouse, pefloxacin at doses up to 150 mg/kg daily was inactive against M. tuberculosis infection: in terms of survival rate the minimal effective dose of ofloxacin against M. tuberculosis infection was 150 mg/kg daily when given by gavage or by incorporation into the mouse diet at a concentration of 0.1 {\%}, but in terms of cfu counts, ofloxacin 150 mg/kg daily only displayed a moderate degree of activity similar to ethambutol 100 mg/kg daily. The therapeutic effects of ofloxacin against M. tuberculosis infection were dose-related: 300 mg/kg daily by gavage or 0.4{\%} in mouse diet displayed much better therapeutic effects than lower dosages. Since the AUC in mice treated with ofloxacin 150 mg/kg daily is close to that in man treated with a clinically tolerated dose-600 mg daily-such a dosage may be only moderately effective against human tuberculosis.",
author = "C. Truffot-Pernot and B. Ji and J. Grosset",
year = "1991",
doi = "10.1016/0041-3879(91)90025-N",
language = "English (US)",
volume = "72",
pages = "57--64",
journal = "Tubercle",
issn = "0041-3879",
publisher = "Churchill Livingstone",
number = "1",

}

TY - JOUR

T1 - Activities of pefloxacin and ofloxacin against mycobacteria

T2 - in vitro and mouse experiments

AU - Truffot-Pernot, C.

AU - Ji, B.

AU - Grosset, J.

PY - 1991

Y1 - 1991

N2 - The minimal inhibitory concentrations for 90% of strains (MIC90) of ofloxacin against Mycobacterium tuberculosis and Mycobacterium xenopi was 2 mg/I. This was three dilutions lower than that of pefloxacin and was well within the range of drug concentrations achievable in man. The antituberculosis activities of both quinolones were independent of resistance of the strains to other antimycobacteriaI agents. Mycobacterium avium-intracellulare was resistant to both compounds with MIC90s greater than 16 mg/l. The maximum serum levels (Cmax) of both compounds increased proportionally with increasing dose size. The terminal elimination half-life (T 1 2) of pefloxacin was longer than that of ofloxacin, but the T 1 2 of both compounds in mice were much shorter than in man. The area under the concentration curve (AUC) of pefloxacin was double than that of ofloxacin. In the mouse, pefloxacin at doses up to 150 mg/kg daily was inactive against M. tuberculosis infection: in terms of survival rate the minimal effective dose of ofloxacin against M. tuberculosis infection was 150 mg/kg daily when given by gavage or by incorporation into the mouse diet at a concentration of 0.1 %, but in terms of cfu counts, ofloxacin 150 mg/kg daily only displayed a moderate degree of activity similar to ethambutol 100 mg/kg daily. The therapeutic effects of ofloxacin against M. tuberculosis infection were dose-related: 300 mg/kg daily by gavage or 0.4% in mouse diet displayed much better therapeutic effects than lower dosages. Since the AUC in mice treated with ofloxacin 150 mg/kg daily is close to that in man treated with a clinically tolerated dose-600 mg daily-such a dosage may be only moderately effective against human tuberculosis.

AB - The minimal inhibitory concentrations for 90% of strains (MIC90) of ofloxacin against Mycobacterium tuberculosis and Mycobacterium xenopi was 2 mg/I. This was three dilutions lower than that of pefloxacin and was well within the range of drug concentrations achievable in man. The antituberculosis activities of both quinolones were independent of resistance of the strains to other antimycobacteriaI agents. Mycobacterium avium-intracellulare was resistant to both compounds with MIC90s greater than 16 mg/l. The maximum serum levels (Cmax) of both compounds increased proportionally with increasing dose size. The terminal elimination half-life (T 1 2) of pefloxacin was longer than that of ofloxacin, but the T 1 2 of both compounds in mice were much shorter than in man. The area under the concentration curve (AUC) of pefloxacin was double than that of ofloxacin. In the mouse, pefloxacin at doses up to 150 mg/kg daily was inactive against M. tuberculosis infection: in terms of survival rate the minimal effective dose of ofloxacin against M. tuberculosis infection was 150 mg/kg daily when given by gavage or by incorporation into the mouse diet at a concentration of 0.1 %, but in terms of cfu counts, ofloxacin 150 mg/kg daily only displayed a moderate degree of activity similar to ethambutol 100 mg/kg daily. The therapeutic effects of ofloxacin against M. tuberculosis infection were dose-related: 300 mg/kg daily by gavage or 0.4% in mouse diet displayed much better therapeutic effects than lower dosages. Since the AUC in mice treated with ofloxacin 150 mg/kg daily is close to that in man treated with a clinically tolerated dose-600 mg daily-such a dosage may be only moderately effective against human tuberculosis.

UR - http://www.scopus.com/inward/record.url?scp=0025963290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025963290&partnerID=8YFLogxK

U2 - 10.1016/0041-3879(91)90025-N

DO - 10.1016/0041-3879(91)90025-N

M3 - Article

C2 - 1909062

AN - SCOPUS:0025963290

VL - 72

SP - 57

EP - 64

JO - Tubercle

JF - Tubercle

SN - 0041-3879

IS - 1

ER -