Penetration of telithromycin (HMR 3647), a new ketolide antimicrobial, into inflammatory blister fluid following oral administration

Namour, F.; Sultan, Eric; Pascual, Marie-Hélène; Lenfant, B.

doi:10.1093/jac/dkf062

Cited by 19 publications

(4 citation statements)

References 4 publications

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“…Pharmacokinetic analyzes support a convenient once‐daily oral dosage regimen [11]. Telithromycin is rapidly absorbed and, at a dose of 800 mg once daily, consistently exceeds plasma minimum inhibitory concentration (MIC) levels for common respiratory pathogens and penetrates well into respiratory tissues [12–14]. Bioavailability does not appear to be affected by food [15] and thus, telithromycin can be administered irrespective of food intake.…”

Section: Introductionmentioning

confidence: 99%

Telithromycin 800 mg once daily for seven to ten days is an effective and well-tolerated treatment for community-acquired pneumonia

Carbon

Moola

Velancsics³

et al. 2003

Clinical Microbiology and Infection

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Section: Introductionmentioning

confidence: 99%

Telithromycin 800 mg once daily for seven to ten days is an effective and well-tolerated treatment for community-acquired pneumonia

Carbon

Moola

Velancsics³

et al. 2003

Clinical Microbiology and Infection

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“…The concentration of telithromycin in plasma was measured from samples taken before and at 80 minutes and 2, 3, 5, and 13 hours after telithromycin administration by use of an API 2000 liquid chromatography–tandem mass spectrometry system (Sciex Division of MDS) 20 . The ion transition monitored was m/z 812 to m/z 655.…”

Section: Methodsmentioning

confidence: 99%

Telithromycin, but not montelukast, increases the plasma concentrations and effects of the cytochrome P450 3A4 and 2C8 substrate repaglinide

Kajosaari

Niemi

Backman

et al. 2006

Clinical Pharmacology & Therapeutics

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Telithromycin, but not montelukast, increases the plasma concentrations and effects of the cytochrome P450 3A4 and 2C8 substrate repaglinide Background and Objective: The antidiabetic repaglinide is metabolized by cytochrome P450 (CYP) 2C8 and CYP3A4. Telithromycin, an antimicrobial agent, inhibits CYP3A4 in vitro and in vivo. Montelukast, an antiasthmatic drug, is a potent inhibitor of CYP2C8 in vitro. We studied the effects of telithromycin, montelukast, and the combination of telithromycin and montelukast on the pharmacokinetics and pharmacodynamics of repaglinide. Methods: In a randomized 4-phase crossover study, 12 healthy volunteers received 800 mg telithromycin, 10 mg montelukast, both telithromycin and montelukast, or placebo once daily for 3 days. On day 3, they ingested a single 0.25-mg dose of repaglinide. Plasma and urine concentrations of repaglinide and its metabolites M1, M2, and M4, as well as blood glucose concentrations, were measured for 12 hours. Results: Telithromycin alone raised the mean peak plasma repaglinide concentration to 138% (range, 91%-209%; P ‫؍‬ .006) and the total area under the plasma concentration-time curve from 0 hours to infinity [AUC(0-ؕ)] of repaglinide to 177% (range, 125%-257%; P < .001) of control (placebo). Telithromycin reduced the AUC(0-ؕ) ratio of the metabolite M1 to repaglinide by 68% (P < .001) and the urinary excretion ratio of M1 to repaglinide by 77% (P ‫؍‬ .001). In contrast to previous estimates based on in vitro CYP2C8 inhibition data, montelukast had no significant effect on the pharmacokinetics of repaglinide or its metabolites and did not significantly alter the effect of telithromycin on repaglinide pharmacokinetics. Telithromycin, unlike montelukast, lowered the maximum blood glucose concentration (P ‫؍‬ .002) and mean blood glucose concentration from 0 to 3 hours (P ‫؍‬ .008) after repaglinide intake, as compared with placebo. Conclusions: Telithromycin increases the plasma concentrations and blood glucose-lowering effect of repaglinide by inhibiting its CYP3A4-catalyzed biotransformation and may increase the risk of hypoglycemia. Unexpectedly, montelukast has no significant effect on repaglinide pharmacokinetics, suggesting that it does not significantly inhibit CYP2C8 in vivo. The low free fraction of montelukast in plasma may explain the lack of effect on CYP2C8 in vivo, despite the low in vitro inhibition constant, highlighting the importance of incorporating plasma protein binding to interaction predictions. (Clin Pharmacol Ther 2006;79:231-42.)

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“…For azithromycin, sustained and high concentrations are also found in the lung (Di Paolo et al 2002 ), tonsils (Foulds et al 1991 ), and prostate (Foulds et al 1990 ) as well as in infl amed blister fl uid (Freeman et al 1994 ). Telithromycin achieves high and prolonged concentrations in the lung (Kadota et al 2002 ;Khair et al 2001 ), nasal mucosa and ethmoid bone (Kuehnel et al 2005 ), tonsils (Gehanno et al 2003 ), female genital tract (Mikamo et al 2003 ), and infl amed blister fl uid (Namour et al 2002 ). Its free concentration in soft tissues (subcutis and muscle) is close to the free serum concentration (Gattringer et al 2004 ;Traunmuller et al 2009 ).…”

Section: Distributionmentioning

confidence: 98%

Macrolides and Ketolides

Bambeke

2013

Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics

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Macrolides and ketolides are characterized by a very wide tissular distribution, which is related to their capacity to accumulate in the acidic compartments of the cells. This property is considered an advantage, because it concentrates the drug at the site of infection. Yet, the low serum levels consecutive to this tissular distribution may favor the selection of resistance. Macrolides are essentially bacteriostatic and ketolides are slowly bactericidal. The pharmacodynamic indice that best predicts effi cacy is the free 24 h-AUC/MIC ratio for both subclasses. Despite their high concentration inside the cells, macrolides and ketolides remain bacteriostatic against intracellular bacteria, with a potency similar to that observed extracellularly. New formulations have been developed to optimize patient's adherence (extended release tablets) or to further increase antibiotic concentration at the site of infection (powders for inhalation).

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Penetration of telithromycin (HMR 3647), a new ketolide antimicrobial, into inflammatory blister fluid following oral administration

Cited by 19 publications

References 4 publications

Telithromycin 800 mg once daily for seven to ten days is an effective and well-tolerated treatment for community-acquired pneumonia

Telithromycin 800 mg once daily for seven to ten days is an effective and well-tolerated treatment for community-acquired pneumonia

Telithromycin, but not montelukast, increases the plasma concentrations and effects of the cytochrome P450 3A4 and 2C8 substrate repaglinide

Macrolides and Ketolides

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