Pharmacokinetics ofIntravenous Cefetamet andOralCefetamet Pivoxil inPatients withRenalInsufficiency

Thepharmacokinetics ofcefetamet after a short intravenous infusion ofcefetamet (515mg)andoral administration of1,000 mg ofcefetamet pivoxil were studied in9healthy subjects andin38patients with various degrees ofrenal impairment. Theresults showedthatcefetamet elimination was dependent on renal function. After intravenous dosing, total body(CLs), renal (CLR), andnonrenal (CLNR) clearances were linearly related tocreatinine clearance (CLCR; r = 0.95, 0.92, and0.59, respectively). Elimination half-life (t112^) was prolonged from2.46 ± 0.33hinnormal subjects to29.1 13.9hinpatients withCLCRof 0.05). After oral administration, the elimination parameters, tl/2,, andCLR,were insignificantly different fromtheintravenous data(P> 0.05). Furthermore, thebioavailability (F)ofcefetamet pivoxil (45 13%)was notaltered byrenal failure (P> 0.05). However, maximumconcentration inplasmaandthetimetoachieve thisvalue were significantly increased (5.860.74 versus14.8 6.14,ug/ml and3.9 ± 1.1versus8.4 1.7h,respectively; P < 0.05). Basedon these observations, itisrecommended thatpatients withCLCRof<10ml/min per 1.73m2 and between 10and39ml/min per1.73 m2begiven one-quarter ofthenormal daily doseeither onceortwice daily. Patients withCLCRbetween 40and80ml/min per1.73m2should receive one-half ofthenormaldosetwice daily. Forpatients withCLCRof<10ml/min per1.73m2,itwouldberecommended thattheyreceive anormal standard doseasa loading doseon day1oftreatment.