HENDERSON-HASSELBALCH EQUATION IS INADEQUATE FOR THE MEASUREMENT OF TRANSMEMBRANE DIFFUSION OF DRUGS AND BUCCAL DRUG ABSORPTION IS A USEFULALTERNATIVE

1. The transmembrane diffusion of weakly acidic or basic drugs is bein g commonly assessed from their degree of ionization or ratio unionized /ionized forms (ratio U/I) as calculated from Henderson-Hasselbalch eq uation (HHEq). 2. Buccal drug absorption (BA) at pH 5-9 has been propo sed as an in vivo model for passage of drugs across lipid membranes. 3 . Area under the curve (AUG) of BA against pH 5-9 of 18 basic drugs ha s been reported to be significantly related to their pH dependent rena l excretion. 4. We have calculated, using HHEq, ratios U/I of 10 weak bases at pH 5-9 and 10 weak acids at pH 4-8, whose percentage BA at th ese pH levels was available in the literature. 5. These ratios were no t related to their %BA at corresponding pH levels. 6. Therefore it is proposed that HHEq is inadequate in the anticipation of transmembrane diffusion of drugs and AUC of %BA of drugs at pH 4-9 is a useful alter native.