Zinc neodecanoate

Endpoint summary

Additional information

Due to the stability conferred by the quaternary carbon, neoacids are relatively resistant to biotransformation and do not readily form bioactive metabolites. Enzymatic removal of the alkyl groups at the quaternary carbon allows for other metabolic processes to occur; mitochondrial beta-oxidation or by cytochrome P450 mediated omega and omega-minus-one oxidation (may be followed by beta-oxidation) to produce acetate. However, since neoacids are not readily metabolized, they are primarily eliminated in the urine as glucuronic acid conjugates, carnitine conjugates or after dealkylation (Brass, 2002).

 

Studies in Animals

Test data exist on three representative neoacids: C5, C7, and C10. In pharmacokinetic studies, C5 was absorbed via oral and dermal routes of exposure. In an in vitro study using porcine skin, the permeability constant (Kp × 103) of C5 was 0.2 cm/min. In comparison, the permeability constant (Kp × 103) of other acids was 1.0 cm/min for C4 (butyric) and 0.31 cm/min for C5 (methyl butyric) (Liron and Cohen, 1984). There is no evidence of marked tissue accumulation of neoacids. Excretion pathways include urine and feces.

 

In a study with C10, rats were fed 100 mg/kg/day of neodecanoic acid for 5 days and followed by a pulse of C-14 labelled neodecanoic acid and assessed every 24 hours for 3 days to determine the distribution and excretion. It was found that under the conditions of the experiment, 70-80% of the administered activity could be accounted for.  Excretion in the urine may expect to range from 50-60% while that in the feces will vary from 40-50%.  In any case, the total of these two will be at least 98%.  The excretion rate falls off rapidly such that less than 1% of dose is expected past 72 hours.  Expired air reaches a peak rate somewhere around 12 hours or earlier.  The total carcass, exclusive of organs, retains less than 1% of the recovered dose.  Intestines had the greatest specific activity and contribute as much as 1% of total dose.  Analysis by thin layer chromatography shows that the bulk of excreted activity is either the original free acid or a material which is readily converted to the acid upon mild hydrolysis.  

 

Limited data suggest that metabolism will vary depending on the neoacid. In rodents and monkeys, C5 does not undergo appreciable metabolism but can form conjugated products which will facilitate excretion from the body (Brass, 2002; Vickers et al., 1985). The C10 neoacid can also form glucuronides that are rapidly eliminated from the body (ExxonMobil, 1968).

 

Studies in Humans

Data exits on neoacid C5 (pivalic acid). Human studies demonstrated the formation of pivaloyl carnitine and urinary pivaloyl carnitine excretion as the main route of C5 elimination (Brass, 2002; Vickers et al., 1985).