Pharmacokinetics of Intravenous Cefetamet and Oral Cefetamet Pivoxil in Human Subjects

Summary

Cefetamet pivoxil (pivoxyl) belongs to the class of orally absorbed prodrug esters that are hydrolysed to the active compound (Cefetamet) on first pass through the gut wall, the liver or both. Intravenously administered cefetamet is eliminated predominantly unchanged in the urine by glomerular filtration. Systemic and renal clearance values for cefetamet were 8.16 and 7.14 L/h (136 and 119 ml/min), respectively. Plasma protein binding is 22% and steady-state volume of distribution (0.29 L/kg) corresponds roughly to the extracellular water space. Cefetamet pivoxil exhibits a significant positive food effect (40 vs 50%) after oral administration. Hence, it is recommended that cefetamet pivoxil is taken with meals. The food effect is not related to changes in gastric pH, since a mixture of aluminium and magnesium hydroxide (Maalox®) or ranitidine did not affect the bioavailability. The predominant renal elimination of cefetamet and the lack of effect of age and disease on cefetamet pivoxil absorption make dosage adjustment in relation to renal dysfunction simple and reliable. The recommended dosage regimen for susceptible bacterial strains in adults with normal renal function is cefetamet pivoxil 500mg twice daily. The same dosage schedule can be used in children, with dose adjustments made according to body surface area.