Cephalothin pharmacokinetics

Substitutions at position 3 of the dihydrothiazine ring play a major role in the overall pharmacokinetic properties and toxicity. For example, the unusually long half-life of ceftriaxone appears to be caused by the presence of a triazine substituted at this position [62]. Cephalosporins such as cephalothin, cephalogly-cin, cephapirin, cephacetiile and cefotaxime share an acetoxymethyl group at the position 3 (Figure 2) and... 

Pharmacokinetic properties of the cephalosporins depend to a considerable extent on their chemical nature, e.g. the substituent R2. The 3-acetoxymethyl compounds such as cephalothin, cephapirin and cephacetrile are converted in vivo by esterases to the antibacterially less active 3-hydroxymethyl derivatives and are excreted partly as such. The rapid excretion means that such cephalosporins have a short half-life in the body. Replacement of the 3-acetoxymethyl group by a variety of groups has rendered other cephalosporins much less prone to esterase attack. For example, cephaloridine has an internally compensated betaine group at position 3 (R2) and is metabolically stable. 

Drug Metabolic Products - Pharmacokinetics Cephalothin was partially converted to deacetylcephalothin after parenteral administration to experimental animals and to man.23 in the dog, initial excretion was distributed equally between cephalothin and its deacetyl metabolite later excretion showed a preponderance of the metabolite over the parent compound. Cephalothin persisted over a longer period of time when administered by the intramuscular route than when given intravenously. In man, the total amount excreted in the urine was... 

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