Pharmacokinetics of oral cefetamet pivoxil (Ro 15-8075) and intravenous cefetamet (Ro 15-8074) in humans: a review

Abstract

Cefetamet pivoxil belongs to the class of orally absorbed pro-drug esters which are hydrolyzed to the active compound (cefetamet) on their first pass through the gut wall and/or the liver. The intravenously administered cefetamet is eliminated predominantly unchanged in the urine by glomerular filtration. Systemic and renal clearance values for cefetamet were 140 and 130 ml/min, respectively. The plasma protein binding is 22%, whereby the only binding protein is albumin. The steady state volume of distribution (0.29 l/kg) corresponds roughly to the extracellular water space which is consistent with other low protein-bound cephalosporins. In general, after intravenous doses, cefetamet follows the kinetic behaviour of a cephalosporin with low protein binding, limited non-renal clearance, and renal clearance that is predominantly due to glomerular filtration, e.g. ceftizoxime, ceftazidime. After oral administration, cefetamet pivoxil shows a significant food effect (F = 41% vs 51%). Hence, cefetamet pivoxil is recommended to be taken after food. The food effect, however, is not of such a magnitude that it will be of clinical consequence when this recommendation is not followed. The food effect is not related to a change in gastric pH because antacids and ranitidine do not affect the absorption of cefetamet pivoxil, although in approximately 20% of the subjects absorption of the drug is delayed. The elimination of cefetamet is directly proportional to renal function. In patients with varying degrees of renal insufficiencies, dosage should be decreased accordingly. Age has no effect on the bioavailability of cefetamet pivoxil. However, the clearance of cefetamet is higher in children and lower in the elderly.