Abstract
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PharmLab™ is an MS-Windows program that computes a time course for drug degradation and can be used
to calculate a pH rate profile for a drug. We have used the program in an educational setting to illustrate and
examine the kinetics of the hydrolysis of ionizable esters as a function of the molecular structure of the ester.
In addition to the educational value, we believe that the simple relationships used to parameterize the program
provide some new insights into the pH rate profile for ester hydrolysis, and could offer an accurate predictive
method, given a broader-based parameterization. The program is based on experimental rate profiles and
on numerical integration of the differential equations that describe the hydrolysis of ionizable esters. The
influence of the pKa of the ionizable group on the experimental rate profiles follows from standard differential
rate equations. Empirical parameters derived as a function of the pKa values of the reactants and products in
the hydrolysis reaction were used to calculate changes in rate constants caused by changes in the molecular
structure. We illustrate the derivation of these parameters for a series of esters structurally similar to
procaine (2-(N,N-diethylamino)ethyl 4-aminobenzoate), and show how the pH rate profiles we obtain can be
interpreted in terms of the structural differences between the esters. The PharmLab™ program 1.0 will be
made available on the USC School of Pharmacy homepage on the World Wide Web.
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