PHARMLAB(TM) - A COMPUTER-PROGRAM FOR THE CALCULATION AND VISUALIZATION OF DRUG DEGRADATION PH RATE PROFILES

PharmLab(TM) 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 f unction of the molecular structure of the ester. In addition to the ed ucational value, we believe that the simple relationships used to para meterize the program provide some new insights into the pH rate profil e for ester hydrolysis, and could offer an accurate predictive method, given a broader-based parameterization. The program is based on exper imental rate profiles and on numerical integration of the differential equations that describe the hydrolysis of ionizable esters. The influ ence of the pK(a) of the ionizable group on the experimental rate prof iles follows from standard differential rate equations, Empirical para meters derived as a function of the pK(a) 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 illust rate the derivation of these parameters for a series of esters structu rally similar to procaine (2-(N,N-diethylamino)ethyl 4-aminobenzoate), and show how the pH rate profiles we obtain can be interpreted in ter ms of the structural differences between the esters. The PharmLab(TM) program 1.0 will be made available on the USC School of Pharmacy homep age on the World Wide Web.