ON THE REACTIONS OF THE CARBAPENEM, MEROPENEM, IN THE SOLUBLE FRACTION OF RAT-KIDNEY

1. When meropenem (I) is incubated with the soluble fraction of rat ki dney or its ultrafiltrate the carbapenem disappears at a rate of 50 nm ol/min per g of kidney at pH 8.4 and 37-degrees-C. 2. In both cases th e kinetics are inconsistent with the reaction being enzymic and the pr oduct has been shown to be a thiol. 3. The same reaction occurs in sim ilar preparations from the kidney of several other mammalian species. 4. The reaction of meropenem with thiols has been investigated: only t hose having a vicinal amino group react rapidly. 5. The product of the reaction with cysteine has been characterized as the amide (III) of t he latter with meropenoic acid (II), the carboxylic acid formed by the hydrolysis of the beta-lactam ring of meropenem. 6. It is postulated that the destruction of meropenem in the soluble fraction of rat kidne y occurs by the non-enzymic reaction of the carbapenem with endogenous cysteine or related thiols. 7. There is no evidence that this reactio n can occur in vivo but it should be considered in the future design o f carbapenems.