The effect of hydroxy metabolites of clarithromycin to the pharmacokinetic parameters, and determination of hydroxy meta
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The effect of hydroxy metabolites of clarithromycin to the pharmacokinetic parameters, and determination of hydroxy metabolites ratio of clarithromycin DURisEHVAR UNAL 1,2, AYSEN FENERCiOGLU3, LATiF OZBAy l,2, BANU OZKIRIM', and DiLEK EROL,,2
'Yeditepe Health Service,GLP Laboratory and GCP Clinics, Acibadem, istanbul, Turkey 2Faculty of Pharmacy, 3Faculty of Medicine, Yeditepe University, Kayisdagr, istanbul, Turkey
Receivedfor publication: November 27, 2008
Key words: Clarithromycin, pharmacokinetics, hydroxy metabolites, humans
SUMMARY Clarithromycin is a broad-spectrum macrolide antibacterial agent which is effective both in vitro and in vivo against the major pathogens responsible for respiratory tract infections. Clarithromycin's principal metabolite is l4-(R) hydroxyc1arithromycin (14OH-c1arithromycin). The other metabolite, namely 14-(S) hydroxyc1arithromycin is inactive. The purpose of this study was to show the hydroxylation ofCLA at the 14position to formthe Rand S epimers and to determine the metabolic ratio of 14ROHCLAICLA and l4S0HCLAICLA for understanding the metabolization. This study suggest that in healthy adults, the individual variations in therapeutic responses to c1arithromycin can be assumed by taking the drugand its metabolites ratios. Clarithromycin and metabolites ratiosincrease during metabolization.
INTRODUCTION Clarithromycin (CLA) is a broad-spectrum macrolide antibacterial agent which is effective both in vitro and in vivo against the major pathogens responsible for respiratory tract infections such as Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella spp., Staphylococcus aureus, Streptococcus pyogenes Moraxella catarrhalis, Streptococcus pneumoniae and Haemophilus influenzae (l). Clarithromycin is a semisynthetic macrolide antibiotic that contains a 14member lactone ring. The recommended dose for treatment of community-acquire upper and lower respiratory tract infections in hospital and community settings is 500-1000 mg-day for 5-14 days. 'Please send reprint requests to: Assoc. Prof. Durisehvar Unal, Yeditepe University, Faculty of Pharmacy, Yeditepe Health Service, GCP Clinic, K6ftiincil Sokak. No:1 Acibadem 34178, Kadikoy, Istanbul, Turkey
The primary metabolic pathways are (i) hydroxylation at the 14-position by cytochrome P450 (CYP)3A isozymes to form the Rand S epimers, (ii) N-demethylation and (iii) hydrolysis of the cladinose sugar. Clarithromycin's principal metabolite, 14-(R) hydroxyclarithromycin (14-0H-clarithromycin), also possesses antibacterial activity and has been reported to be more active than the parent drug against many strains of H. Influenzae. The other metabolite, namely 14-(S) hydroxyclarithromycin is inactive (2,3). The maximal plasma concentrations (Cmax) of clarithromycin and of its 14-hydroxy metabolite following a single oral dose are dose dependent and are achieved within 3 hours. The maximal plasma concentrations of clarithromycin after single doses of 250 and 500 mg were 0.78±0.25 and 2.l2±0.83 mg/L, respectively. The time to peak concentra
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