Henderson-Hasselbalch equation is inadequate for the measurement of transmembrane diffusion of drugs and buccal drug absorption is a useful alternative.
1. The transmembrane diffusion of weakly acidic or basic drugs is being commonly assessed from their degree of ionization or ratio unionized/ionized forms (ratio U/I) as calculated from Henderson-Hasselbalch equation (HHEq). 2. Buccal drug absorption (BA) at pH 5-9 has been proposed as an in vivo model for passage of drugs across lipid membranes. 3. Area under the curve (AUC) of BA against pH 5-9 of 18 basic drugs has been reported to be significantly related to their pH dependent renal 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 these pH levels was available in the literature. 5. These ratios were not 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 alternative.
Randhawa
M A
MA
Department of Pharmacology and Therapeutics, Rawalpindi Medical College, Pakistan.
Iqbal
A
A
Nasimullah
M
M
Akhtar
M
M
Yousaf
S M
SM
Turner
P
P
D000042:Absorption; D000143:Acids / Q000378:metabolism; D004058:Diffusion; D006863:Hydrogen-Ion Concentration; D008566:Membranes / Q000378:metabolism; D009061:Mouth Mucosa / Q000378:metabolism*; D010599:Pharmacokinetics
D000143:Acids