PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel

Abstract

This study presents PKSolver, a freely available menu-driven add-in program for Microsoft Excel written in Visual Basic for Applications (VBA), for solving basic problems in pharmacokinetic (PK) and pharmacodynamic (PD) data analysis. The program provides a range of modules for PK and PD analysis including noncompartmental analysis (NCA), compartmental analysis (CA), and pharmacodynamic modeling. Two special built-in modules, multiple absorption sites (MAS) and enterohepatic circulation (EHC), were developed for fitting the double-peak concentration–time profile based on the classical one-compartment model. In addition, twenty frequently used pharmacokinetic functions were encoded as a macro and can be directly accessed in an Excel spreadsheet. To evaluate the program, a detailed comparison of modeling PK data using PKSolver and professional PK/PD software package WinNonlin and Scientist was performed. The results showed that the parameters estimated with PKSolver were satisfactory. In conclusion, the PKSolver simplified the PK and PD data analysis process and its output could be generated in Microsoft Word in the form of an integrated report. The program provides pharmacokinetic researchers with a fast and easy-to-use tool for routine and basic PK and PD data analysis with a more user-friendly interface.

Introduction

Analysis of drug concentration–time or drug effect-concentration data plays an important role in pharmacokinetic (PK) and pharmacodynamic (PD) research. Tedious mathematical calculations, optimization algorithms, and graph plotting are essential for pharmacokinetic data analysis. To streamline such analyses, various software packages have been developed and marketed. More often than not, many of these commercially available packages, such as WinNonlin and Kinetica, are expensive or have a steep learning curve. Therefore, it is worthwhile exploring the possibility of cost-effective and easy-to-use alternatives for PK/PD analysis.

Microsoft Excel has been widely used by scientists for data collection, calculation, and analysis. While custom designed spreadsheet templates can be easily built, sophisticated and highly customizable macros can also be compiled using Excel Visual Basic for Applications (VBA). Several templates and add-in programs have already been developed for biological and medicinal applications [1], [2], [3], [4]. In pharmaceutical science, Excel has been adopted for pharmacokinetic data analysis such as noncompartmental analysis (NCA) calculation [5], [6], nonlinear fitting analysis [7], complex pharmacokinetic model simulation [8], bioavailability/bioequivalence (BA/BE) simulation [9], in vitro/in vivo correlation (IVIVC) analysis [10], [11] and modeling of quantitative structure–pharmacokinetic relationships [12]. However, some of these programs have only a few NCA calculation functions [5], [6] or were built as predetermined spreadsheet templates limiting data input in specified ranges as well as the amount of data. These data sets are usually paired concentration–time data and often have limited data sets (for example, “up to 30 plasma samples” [7]); thus, most of these programs lack flexibility. Moreover, according to previous reports [13], [14], it is time-consuming to perform a step-by-step nonlinear fitting because only a single set data can be fitted using Excel's SOLVER each time. Additionally, PK models for analyzing double-peak concentration–time data are rarely embedded in popular, commercially available packages. Thus it is highly desirable to have these models coded as an add-in program with user-friendly interface, predefined menus and forms for easy recall.

In this study, a VBA program, PKSolver, was developed for a range of applications for PK/PD data analysis including: (1) noncompartmental analysis for plasma data after extravascular administration, IV bolus injection, and IV infusion; (2) compartmental modeling of concentration–time data; (3) compartmental model analysis for double-peak concentration–time curves; (4) modeling of pharmacodynamic data; and (5) twenty frequently used pharmacokinetic functions that can be invoked within an open spreadsheet. Last, but not least, all the features mentioned above can be programmed to run in batches and can subsequently generate integrated report in MS Word documents with only a few simple operations.