Les effets indésirables des antituberculeux: épidémiologie, mécanismes et conduite à tenir

Aouam, Karim; Chaabane, Amel; Loussaief, Chokri; Romdhane, F. Ben; Boughattas, Naceur A.; Chakroun, M.

doi:10.1016/j.medmal.2006.12.006

Cited by 37 publications

(22 citation statements)

References 51 publications

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“…Although the role of such treatment is denoted as "unclear" by the WHO, it has been shown to achieve earlier and persistent sputum clearance and the best radiological improvement (44). There may be concerns about the tolerability of such higher doses, as some data indicate that INH neurotoxicity and hepatotoxicity may increase with increasing drug exposure (45,46). Further research is required to clarify the potential benefits and risks of high-dose INH treatment.…”

Section: Discussionmentioning

confidence: 99%

Population Modeling and Simulation Study of the Pharmacokinetics and Antituberculosis Pharmacodynamics of Isoniazid in Lungs

Lalande

Bourguignon

Bihari

et al. 2015

Antimicrob Agents Chemother

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Among first-line antituberculosis drugs, isoniazid (INH) displays the greatest early bactericidal activity (EBA) and is key to reducing contagiousness in treated patients. The pulmonary pharmacokinetics and pharmacodynamics of INH have not been fully characterized with modeling and simulation approaches. INH concentrations measured in plasma, epithelial lining fluid, and alveolar cells for 89 patients, including fast acetylators (FAs) and slow acetylators (SAs), were modeled by use of population pharmacokinetic modeling. Then the model was used to simulate the EBA of INH in lungs and to investigate the influences of INH dose, acetylator status, and M. tuberculosis MIC on this effect. A three-compartment model adequately described INH concentrations in plasma and lungs. With an MIC of 0.0625 mg/liter, simulations showed that the mean bactericidal effect of a standard 300-mg daily dose of INH was only 11% lower for FA subjects than for SA subjects and that dose increases had little influence on the effects in either FA or SA subjects. With an MIC value of 1 mg/liter, the mean bactericidal effect associated with a 300-mg daily dose of INH in SA subjects was 41% greater than that in FA subjects. With the same MIC, increasing the daily INH dose from 300 mg to 450 mg resulted in a 22% increase in FA subjects. These results suggest that patients infected with M. tuberculosis with low-level resistance, especially FA patients, may benefit from higher INH doses, while dose adjustment for acetylator status has no significant impact on the EBA in patients with low-MIC strains.

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Section: Discussionmentioning

confidence: 99%

Population Modeling and Simulation Study of the Pharmacokinetics and Antituberculosis Pharmacodynamics of Isoniazid in Lungs

Lalande

Bourguignon

Bihari

et al. 2015

Antimicrob Agents Chemother

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“…Several authors reported that INH taken alone, in normal doses, was responsible for liver biochemical markers disorders. Aouam et al (2007) reported hepatic disorders in 10 to 20% of users in Tunisia, and Blumberg et al (2003) reported 0.5 to 2% of patients in the USA. When RIF was associated with INH, this liver disorder affected a greater number of patients (Aouam et al, 2007) and 2.5 to 6% of patients (Blumberg et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Aouam et al (2007) reported hepatic disorders in 10 to 20% of users in Tunisia, and Blumberg et al (2003) reported 0.5 to 2% of patients in the USA. When RIF was associated with INH, this liver disorder affected a greater number of patients (Aouam et al, 2007) and 2.5 to 6% of patients (Blumberg et al, 2003). The work of Aouam et al (2007) also showed that INH + RIF + PZA was responsible for cytolytic hepatitis in 0.5 to 10% of treated patients.…”

Section: Introductionmentioning

confidence: 99%

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Hepatoprotective effects of methanol extract of Alchornea cordifolia leaves against anti-tubercular drugs induced hepatotoxicity in rats

Etienne¹,

Landry²,

Genevieve³

et al. 2017

Afr. J. Pharm. Pharmacol.

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Alchornea cordifolia has been shown to be hepatoprotective against hepatotoxicity induced by high dose paracetamol in a model animal. However, its hepatoprotective effects against the hepatotoxicity induced by anti-tubercular drugs have not yet been studied, whereas anti-tubercular drugs are known to be hepatotoxic at therapeutic dose. The aim of this work was to evaluate the hepatoprotective effect of a methanol extract of A. cordifolia leaves in order to overcome hepatotoxicity induced by antitubercular drugs. Isoniazid, Rifampicin and Pyrazinamid have been used to induce hepatotoxicity in rats. The animals were administered hepatotoxic agent. Two hours later they were given methanol extract of A. cordifolia (MEAC) leaves or silymarin. One group of animals received only the antitubercular drugs, one group received MEAC only and another group received physiological saline. The animals were thus treated for 10 consecutive days. Blood sample was taken on the 11th day for evaluation of the biochemical parameters, as well as markers of hepatotoxicity. Isoniazid increased transaminases (ALT and AST), MEAC and silymarin reduced these biochemical parameters, Isoniazid + Rifampicin increased ALT and AST levels, MEAC reduced alanine transaminase (ALT) and aspartate transaminase (AST) levels, Isoniazid + Rifampicin + Pyrazinamid combination resulted in significant ALT elevation and MEAC reduced the ALT levels. MEAC alone did not significantly alter ALT and AST values. Phytochemical screening revealed the presence of flavonoids, polyphenols, saponosides and alkaloids. A. cordifolia leaves would thus have a protective effect against anti-tubercular drugs induced hepatotoxicity in rats.

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“…Aouam et al (2007) [17] reported hepatic disorders in 10% to 20% of users in Tunisia with INH at therapeutic dose, when Blumberg et al (2003) [13] reported disturbances of hepatic markers in 0.5% to 2% of patients in the USA. When the RIF was associated with the INH, this disturbance affected more patients [17], which was 2.5% to 6% of the patients according to Blumberg et al (2003) [13].…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Activity and Hepatoprotective Effect of an Aqueous Extract of <i>Alchornea cordifolia</i> Leaves

Effo¹,

Kouakou²,

Irie-N’Guessan³

et al. 2017

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Alchornea cordifolia is a medicinal plant, whose ethanolic and methanolic extracts have shown antioxidant activity which could confer hepatoprotective effect, knowing that liver cells are attacked by free radicals. The hepatoprotective effect of these extracts has been demonstrated in models of hepatotoxicity induced by paracetamol high doses in animals. However, anti-tubercular drugs at the usual dose present hepatotoxicity risk. Could Alchornea cordifolia help to limit hepatotoxicity induced by anti-tubercular drugs? This work aimed to evaluate the antioxidant activity and the hepatoprotective effect of an aqueous extract of A. cordifolia leaves (AEAC). The antioxidant activity of A. cordifolia leaves was studied in vitro by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals scavenging assay and by the iron reduction ability. A phytochemical screening was carried out to identify the chemical groups that could be responsible for this activity. The hepatoprotective effect was demonstrated in a model of hepatotoxicity induced by isoniazid and rifampicin in rats. Two hours after induction of hepatotoxicity, the animals were orally administered the AEAC at 200 mg/kg, 400 mg/kg, 800 mg/kg for 10 consecutive days. A blood sample was taken on the 11 th day for the evaluation of transaminases, markers of hepatic cytolysis. A totally of 96 rats were used in this study. AEAC showed dose-dependent antioxidant activity. Phytochemical screening revealed the presence of flavonoids, tannins and alkaloids. Administrated alone, aqueous extract of A. cordifolia leaves didn't modificate the transaminases, isoniazid and the isoniazid + rifampicin combination resulted in increasing transaminases (ALT and AST) by more than 48%. AEAC at 800 mg/kg reduced AST and ALT levels by more than 45%. AEAC at 200 mg/kg and 400 mg/kg decreased ALT more than 40%. Knowing that antioxidant activity protects liver, the AEAC may by its antioxidant activity, contribute to protect against the hepatotoxicity induced by an-

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Les effets indésirables des antituberculeux: épidémiologie, mécanismes et conduite à tenir

Cited by 37 publications

References 51 publications

Population Modeling and Simulation Study of the Pharmacokinetics and Antituberculosis Pharmacodynamics of Isoniazid in Lungs

Population Modeling and Simulation Study of the Pharmacokinetics and Antituberculosis Pharmacodynamics of Isoniazid in Lungs

Hepatoprotective effects of methanol extract of Alchornea cordifolia leaves against anti-tubercular drugs induced hepatotoxicity in rats

Antioxidant Activity and Hepatoprotective Effect of an Aqueous Extract of <i>Alchornea cordifolia</i> Leaves

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Les effets indésirables des antituberculeux: épidémiologie, mécanismes et conduite à tenir

Cited by 37 publications

References 51 publications

Population Modeling and Simulation Study of the Pharmacokinetics and Antituberculosis Pharmacodynamics of Isoniazid in Lungs

Population Modeling and Simulation Study of the Pharmacokinetics and Antituberculosis Pharmacodynamics of Isoniazid in Lungs

Hepatoprotective effects of methanol extract of Alchornea cordifolia leaves against anti-tubercular drugs induced hepatotoxicity in rats

Antioxidant Activity and Hepatoprotective Effect of an Aqueous Extract of &lt;i&gt;Alchornea cordifolia&lt;/i&gt; Leaves

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Antioxidant Activity and Hepatoprotective Effect of an Aqueous Extract of <i>Alchornea cordifolia</i> Leaves