Pharmacokinetics of telithromycin: application to dosing in the treatment of community-acquired respiratory tract infections.
BACKGROUND
Telithromycin is the first ketolide anti bacterial approved for treating community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute bacterial sinusitis in adults. The purpose of this article is to review the main pharmacokinetic properties of telithromycin and their application to the treatment of these infections.


METHODS
Sources of information were identified through a Medline search (up to March 2005).


RESULTS
The absolute oral bioavailability of telithromycin is approximately 57%, which is unaffected by food intake. At the recommended 800 mg once-daily oral dosing regimen, telithromycin reaches a steady-state concentration of approximately 2 microg/mL in plasma and has an elimination half-life of approximately 10 hours. Telithromycin shows extensive tissue distribution and penetrates effectively into bronchopulmonary tissue and epithelial lining fluid. Since elimination of telithromycin occurs via multiple pathways--the highest proportion (70%) through metabolism--impairment of a single pathway has a limited impact on telithromycin exposure. Dose adjustments are unnecessary in elderly patients or in individuals with hepatic impairment or mild to moderate renal impairment. A reduced dose could be recommended in patients with severe renal impairment. Telithromycin is metabolized primarily in the liver, approximately half of which is via the cytochrome P450 (CYP) 3A4 system. Telithromycin AUC(0-24 h) increased by 1.5- to 2.0-fold in the presence of itraconazole and ketoconazole. Administration of telithromycin with drugs metabolized via CYP3A4 may result in increased exposure to the co-administered drug, as shown for simvastatin (5.3-fold) and midazolam (6-fold). Co-administration of telithromycin minimally increases (1.2- to 1.4-fold) exposure to theophylline, digoxin, and metoprolol. Although telithromycin does not affect the pharmacokinetics of warfarin, consideration should be given to monitoring prothrombin times/INR in patients receiving telithromycin and oral anticoagulants simultaneously.


CONCLUSIONS
Overall, the pharmacokinetic/pharmaco dynamic properties of telithromycin indicate that this ketolide antibacterial is a valuable and convenient treatment option for community-acquired respiratory tract infections.
Ciervo
Carman A
CA
University of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, Stratford, NJ 08084, USA. ciervoca@umdnj.edu
Shi
Jun
J
D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D001991:Bronchitis / Q000188:drug therapy; D017714:Community-Acquired Infections / Q000188:drug therapy*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D048628:Ketolides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007674:Kidney Diseases / Q000378:metabolism; D011014:Pneumonia / Q000188:drug therapy; D012141:Respiratory Tract Infections / Q000188:drug therapy*; D012852:Sinusitis / Q000188:drug therapy
D000900:Anti-Bacterial Agents; D048628:Ketolides; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C106791:telithromycin