Pharmacokinetics of intravenous cefetamet and oral cefetamet pivoxil in patients with hepatic cirrhosis

Hayton, William L.; Kneer, Johannes; Blouin, Robert A.; Stoeckel, Klaus

doi:10.1128/aac.34.7.1318

Cited by 13 publications

(2 citation statements)

References 19 publications

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“…Pharmacokinet. 25 (3) 1993 and 12 patients (mean age 47.9 ± 6.0 years, mean bodyweight 76.7 ± 1O.8kg) with hepatic cirrhosis without ascites (Hayton et al 1990). The diagnosis of hepatic cirrhosis was consistent with lower values of phenazone (antipyrine) clearance [32 ± 13 vs 67 ± 27 ml/min (1.92 ± 0.78 vs 4.02 ± 1.62 L/h)] and aminophenazone (aminopyrine) breath test values (16.7 ± 10.4% of the administered dose was expired via the breath as 14C02 over 2 hours; normal values for healthy volunteers would be 40 to 70%).…”

Section: Liver Impairmentmentioning

confidence: 99%

Cefetamet Pivoxil Clinical Pharmacokinetics

Blouin

Stoeckel

1993

Clinical Pharmacokinetics

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Cefetamet pivoxil is an orally absorbed prodrug ester of the microbiologically active cephalosporin, cefetamet. The prodrug ester is completely hydrolysed to the active compound cefetamet on its first pass through the gut wall, the liver or both. Cefetamet is classified as a third generation cephalosporin with excellent activity against streptococci, Enterobacteriaceae, Neisseria and Haemophilus species. It has enhanced stability against beta-lactamases compared with penicillins and first and second generation cephalosporins. The antibacterial spectrum is comparable with that of cefotaxime except for its poor activity against staphylococci. Following a 20-minute zero-order intravenous infusion, cefetamet had a rapid distribution phase followed by a monoexponential decline. The average pharmacokinetic parameters from 152 healthy volunteers were: total body clearance 136 ml/min (8.16 L/h); renal clearance 119 ml/min (7.14 L/h); nonrenal clearance 17 ml/min (1.02 L/h); volume of distribution at steady-state 0.29 L/kg; terminal elimination half-life 2.2 hours; 88% of the dose recovered in the urine. Cefetamet is not extensively bound to plasma proteins. Consequently, these data indicate that cefetamet is predominantly eliminated unchanged by the kidney via glomerular filtration with possibly a minor component of tubular secretion. Cefetamet has a relatively small apparent volume of distribution consistent with that of other beta-lactam antibiotics. Results following ascending intravenous doses of cefetamet in healthy young male volunteers demonstrated that the pharmacokinetics of intravenous cefetamet are independent of the dose. The absolute bioavailability of cefetamet tablets following oral cefetamet pivoxil administration is enhanced by the presence of food. Under fed conditions, 50 to 60% of the final oral dose is absorbed into the systemic circulation. This food effect is observed when cefetamet pivoxil is administered within 1 hour of a meal. Food also produces a slight delay in the time to reach peak plasma concentrations of this drug. Changes in fluid volume intake with cefetamet pivoxil administration have no effect on the bioavailability of this drug. Similar absorption characteristics have been observed for all of the tablet dosage formulations studied during clinical development. The absolute bioavailability of the final syrup dosage formulation was between 38 and 47%. Little improvement in the bioavailability of this preparation has been observed with food. The absorption and disposition of cefetamet in human subpopulations [i.e. children, elderly (< 75 years of age), renal impairment, liver disease and patients taking concomitant drugs] have been studied extensively. Only impaired renal function appears to significantly alter the elimination of this drug.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Liver Impairmentmentioning

confidence: 99%

Cefetamet Pivoxil Clinical Pharmacokinetics

Blouin

Stoeckel

1993

Clinical Pharmacokinetics

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“…The dosage can be corrected using the measured or estimated creatinine clearance [29]. Hepatic cirrhosis does not significantly influence the pharmacokinetics of cefetamet pivoxil [30].…”

Section: Cefpodoxime Proxetilmentioning

confidence: 99%

Future directions in antimicrobial chemotherapy

Janknegt

1992

Pharmaceutisch Weekblad Scientific Edition

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New developments in the treatment of bacterial infections are discussed. The most important developments include oral broad-spectrum cephalosporin derivatives and extended-spectrum injectable cephalosporins with improved activity against Gram-positive bacteria. Meropenem is a new carbapenem agent with markedly improved activity against Gram-negative bacteria. Many fluoroquinolones are in various phases of development. The most interesting new compound is sparfloxacin. Azithromycin is a new macrolide which, because of its very long half-life, attains very high levels in most tissues. Potential uses of the newer agents are discussed.

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