• Journal of Pharmaceutical Investigation
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• v.18 no.4
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• pp.197-201
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• 1988

Pivaloyloxymethyl ester of cefoperazone was synthesized by treating sodium cefoperazone with chloromethyl pivalate and its chemical structure was determined by spectroscopic trials. The pharmaceutical properties of the ester were investigated to assess its potential as a prodrug of cefo perazone. Cefoperazone pivaloyloxymethyl ester was microbiologically inactive itself in vitro, but hydrolyzed into the parent drug in vivo. After a single oral dose of each drug to rabbits, serum concentrations of cefoperazone were determined by high performance liquid chromatographic assay. The ester showed higher and more sustained blood level than cefoperazone. Therefore, the total area under the serum concentration-time curve of the derivative was 16.8 times larger than that of the parent drug.

• Journal of Pharmaceutical Investigation
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• v.19 no.1
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• pp.21-27
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• 1989

Kinetic and thermodynamic aspects of the interface transfer of cefoperazone and its pivaloyloxymethyl ester were studied in a two-phase system composed of aqueous buffers and n-octanol by using the absolute reaction rate theory. In terms of the net thermodynamic parameters for the process, ${\Delta}S$ increased and ${\Delta}F$ decreased as the lipophilicity increased. With the increased ratio of forward $(k_f)$ to backward rate constants $(k_b)$, the ester was more lipophilic than cefoperazone, but the aqueous solubility was reduced.