title: Multi-pH QSAR: II. Regression Analysis Sensitive Enough to Determine the Transition-State pKa of Human Buccal Absorption.
abstract: An analysis of published human buccal absorption data of an acid and a base at six pH values extends multi-pH QSAR to an extreme: QSAR on a single compound. The compounds analyzed are 4-n-hexylphenylacetic acid and propranolol. This analysis might be considered as much an analysis of the model as the compound, itself. Ionizable compounds undergo a pKa change in the process of absorption. Multi-pH QSAR allows determination of the pKa of the presumed rate-limiting step for absorption, which we label the transition-state pKa (pKa (TS) ). Comparison of the pKa (TS) with the corresponding aqueous and membrane pKa values provides the extent of molecular penetration at the transition state. It is 49 % of the path length for the arylacetic acid and 73 % for propranolol.
authors.affiliation: BIOpKa, 3416 Ebba Street, White Bear Lake, MN 55110, USA fax: 651-7707831. rascherrer@biopKa.com.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Scherrer
keywords: Buccal absorption; Ion pairs; Multi-pH QSAR; Structure-activity relationships; Transition state