When meropenem (I) is incubated with the soluble fraction of rat kidney or its ultrafiltrate the carbapenem disappears at a rate of 50 nmol/min per g of kidney at pH 8.4 and 37 degrees C. 2. In both cases the kinetics are inconsistent with the reaction being enzymic and the product has been shown to be a thiol. 3. The same reaction occurs in similar preparations from the kidney of several other mammalian species. 4. The reaction of meropenem with thiols has been investigated: only those having a vicinal amino group react rapidly. 5. The product of the reaction with cysteine has been characterized as the amide(III) of the 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 kidney occurs by the non-enzymic reaction of the carbapenem with endogenous cysteine or related thiols. 7. There is no evidence that this reaction can occur in vivo but it should be considered in the future design of carbapenems.
