Toxicological Issues with Pivalate Prodrugs
The incorporation of pivalate (trimethylacetic acid) through an ester linkage to a bioactive molecule is an effective and established strategy for engineering a drug with improved systemic delivery of the bioactive molecule (Beaumont et al., 2003). Compared with the native molecule, the pivalate-containing prodrug will have higher lipophilicity and, thus, will cross lipid biomembranes more readily. The ester is then hydrolyzed to form the desired bioactive molecule and pivalate. Hydrolysis is catalyzed by a spectrum of enzymes found in the blood and several organs, including the intestine and liver (Cook et al., 1995; Takahashi et al., 1995; Beaumont et al., 2003).
KeywordsAdefovir Dipivoxil Carnitine Concentration Carnitine Transport Total Carnitine Muscle Carnitine
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