Journal of Targeted Drug Delivery

Clinical Pharmacology of Rifampin in Infants and Children

Author(s): Gian Maria Pacifici

Rifampin is a macrocyclic antibiotic important in the treatment of mycobacterial diseases. This antibiotic is bacteriastatic as inhibits the transcription of DNA to RNA by binding to the β-subunit of bacterial RNA-polymerase (rpoB) to form a stable drug-enzyme complex. Rifampin enters bacilli in a concentration depended manner, achieving steady-state concentration within 15 min. This antibiotic inhibits the growth of most gram-positive and gram-negative microorganisms, and it is used to treat tuberculosis, leprosy, brucellosis, Mycobacterium kansasii, mycobacterium marinum, Mycobacterium uclerans, Mycobacterium malmoense, and Mycobacterium Haemophilus diseases. Rifampin is an effective and safe antibiotic in infants and children. Two formulations of rifampin are available, one for oral and other one for intravenous administration. In infants, the dose of rifampin is 10 to 20 mg/kg every 24 hours (oral administration) and 5 to 10 mg/kg every 12 hours (intravenous administration). To treat tuberculosis rifampin is co-administered with isoniazid. The fixed dose of rifampin/isoniazid is 60/60 mg per dispersible tablets. Concomitant administration of rifampin and isoniazid induces hepatotoxicity in children. Rifampin has been used to treat staphylococcal, bacterial meningitis, tuberculous meningitis, and Haemophilus infections. The pharmacokinetics of rifampin has been extensively studied in infants and children. Rifampin is extensively metabolized by different cytochromes P-450 and the metabolites are: 25-O-desecetyrifampicin and 3-formylrifamycin SV, 25-O-desecetyrifampicin, is the mean metabolite. Rifampin is a potent inducers of several cytochromes P-450. Rifampin, and its metabolites, are mainly excreted in the bile and eliminated with the faeces. Little is known about the bacterial resistance to rifampin, it is approximately < 20% and is higher in younger than older patients (P-value = 0.003). The aim of this study is to review the published data on rifampin-dosing, effects, metabolism, pharmacokinetics, and bacterial-resistance of rifampin in infants and children.

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