cefamandole and Body-Weight

From a search of the available literature, a database of 22 drugs of all charge types and several different therapeutic classes was compiled to compare rat and human biliary clearance data. Dog biliary excretion data were also found for nine of the drugs. For 19 of the 22 drugs (86%), rat unbound biliary clearance values, when normalized for body weight, exceeded those for humans by factors ranging from 9 to over 2500-fold, whereas human/dog differences were much less dramatic. It was possible to define hepatic uptake and efflux transporter involvement for many of the drugs. On the basis of the findings, it is postulated that regardless of the biliary efflux transporters implicated, when drugs do not require active hepatic uptake to access the liver there may be fairly insignificant differences in rat, dog, and human biliary clearance. Conversely, when the organic anion-transporting polypeptide drug transporters are involved, one may expect at least a 10-fold discrepancy in rat to human biliary clearance normalized for body weight and corrected for plasma protein binding.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Bile; Body Weight; Dogs; Drug Administration Routes; Humans; Liver; Membrane Transport Proteins; Multidrug Resistance-Associated Protein 2; Multidrug Resistance-Associated Proteins; Neoplasm Proteins; Organic Anion Transporters; Pharmaceutical Preparations; Protein Binding; Rats; Species Specificity

The testicular toxicity of cefamandole, a beta-lactam antibiotic with an N-methylthiotetrazole side chain, was evaluated in neonatal rats. Cefamandole caused delayed maturity of the germinal epithelium of neonatal rats when given on Postpartum Days 6 through 36. In rats given daily subcutaneous injections of 1000 mg/kg during this period, the most mature germinal cells were acrosome phase spermatids, whereas control rats had spermatids in the maturation phase. In studies of specific developmental phases, the effect of 1000 mg/kg daily cefamandole was primarily on the initial waves of spermatogonia during the period of rapid development (Postpartum Days 4 through 13). In animals treated from birth to Postpartum Day 8 and evaluated sequentially on Postpartum Days 5 through 9, there were no morphologically discernible effects on the transformation of gonocytes to immature spermatogonia, but there were slight degenerative changes in the first waves of developing spermatogonia. Cefamandole, 1000 mg/kg daily, given Postpartum Days 14 through 18 during the initial phase of spermatocyte development, also caused a slight degenerative change of the initial waves of pachytene spermatocytes. The significance of the findings in neonatal rats is unknown because differences in spermatogenic development between rat and human preclude direct extrapolation of the effects of cefamandole in neonatal rats to effects in humans.

Topics: Aging; Animals; Body Weight; Cefamandole; Male; Organ Size; Rats; Rats, Inbred Strains; Spermatogenesis; Testis

1.0 g cefamandol was injected in 25 patients with various degrees of renal function. Half-life and distribution volume of this antibiotic and the glomerular filtration rate (GFR) were then measured. The distribution volume was 18.5 +/- 3.5% of body weight, similar to the extracellular space. Half-life and GFR were related in a way which could be expressed in the formula: half-life = 400 sqaure root GFR. Levels of blood concentration of cefamandol could be estimated from half-life and GFR, with the construction of "isoconcentration dosages", by which it is possible to achieve levels similar to those in normal subjects receiving a normal dosage.

Topics: Body Weight; Cefamandole; Cephalosporins; Extracellular Space; Female; Glomerular Filtration Rate; Half-Life; Humans; Kidney Failure, Chronic; Kinetics; Male