Disposition ofRoxithromycin inPatients withNormaland Severely Impaired RenalFunction

data wereanalyzed intermsofa one-ortwo-compartment oralabsorption modelutilizing nonlinear regression analysis. Theterminal elimination half-life was significantly prolonged inthegroup with severely impaired renal function (15.54.7h)compared withthatofthegroup withnormalrenal function (7.92.5h).Apparent total bodyclearance was significantly reduced intherenally impaired (25.310.5 ml/min) inrelation tothegroupwithnormal renal function (48.811.1ml/min). Thefirst-order absorption rateconstants andapparent volumes ofdistribution didnotdiffer between thetwogroups.Thesedataindicate that thedisposition ofroxithromycin issignificantly delayed insubjects withCLcRsof<15ml/min andsuggest thattheroxithromycin dosing interval bedoubled forthese patients. Roxithromycin isan investigational macrolide antibiotic whichissimilar toerythromycin inchemical structure and antimicrobial spectrum ofactivity (1,5,10). Preliminary data foranimals andhumanssuggestthatoralroxithromycin administration attains concentrations inplasma higher than thoseoferythromycin because ofacidstability andthus better absorption (13). Furthermore, theterminal elimination half-life (t1/2.) is7to10h insubjects withnormal renal function compared withabout2hforerythromycin (13). Although only15%ofroxithromycin iseliminated renally unchanged, recentdatawithother compounds havedemonstrated markedalterations innonrenal disposition inthe presenceofdecreased renal function (2). Therefore, this study was designed toevaluate andcomparethedispositions ofroxithromycin insubjects withnormal andseverely impaired renal function.