630 3. DEHYDROACETATE 



in kidney, muscle, or testis (Barman et al., 1963). The rabbit apparently 

 metabolizes dehydroacetate more readily than the rat. The absence of glu- 

 curonides or ethereal sulfates in the urine was confirmed. The urinary pyrone 

 metabolite is probably the 3-carboxylate of triacetic acid lactone. 



Dehydroacetate is excreted by the kidney quite slowly. This could be due 

 to the binding of a major fraction in the plasma to protein, or to active 

 resorption by the tubules; both actually occur. The fraction bound to plasma 

 proteins depends on the species and the dehydroacetate concentration 

 (Woods et al., 1950) (some averages are shown in the accompanying tabu- 

 lation). However, even when the renal excretion is corrected for the amount 



bound, it is evident that this is not the primary factor in the slow excretion. 

 Dehydroacetate is resorbed through the tubules to about the same extent 

 as water (98-99%). Since the ring structure of dehydroacetate is identical 

 to the pyranose form of glucose, it was felt that transport by the glucose 

 system might occur, but phlorizin, at a concentration that markedly in- 

 hibits glucose transport, does not alter dehydroacetate resorption. The re- 

 lationship between the transport of dehydroacetate and the effects of dehy- 

 droacetate on other transport mechanisms, if any, is not clear. 



Both dehydroacetic acid and its sodium salt are absorbed rapidly when 

 given orally, peak plasma concentrations occurring in 90-120 min. It can 

 be detected in the blood 3 4 days after single doses, and when administered 

 chronically many days are required for the plasma level to drop to negli- 

 gible concentrations. The distribution of dehydroacetate in the tissues (Ta- 

 ble 3-1) and its variation with time illustrate the complexities of the factors 

 governing penetration and binding. The low concentration in the central 

 nervous system and the relatively high level in spinal fluid are surprising. 

 The biliary circulation of dehydroacetate may play a minor role in retain- 

 ing it in the body. 



Dehydroacetate is secreted in the saliva at a reasonably high concentra- 

 tion, an injection of 5 mg intraperitoneally in the rat giving salivary levels 

 of 0.25-0.33 mM at 2-6 hr (Zipkin and McClure, 1958), roughly about half 

 the plasma concentration. Dehydroacetate has been incorporated into tooth- 

 pastes to inhibit bacterial growth and caries. However, it has been found 



