Abstract
Relative bioavailability study of tolterodine in healthy human volunteers was done
using saliva and plasma matrices in order to investigate the robustness of using saliva
instead of plasma as a surrogate for bioavailability and bioequivalence of class III
drugs according to the salivary excretion classification system (SECS). Saliva and
plasma samples were collected up to 16 h after 2 mg oral dose. Saliva and plasma pharmacokinetic
parameters were calculated by non compartmental analysis using Kinetica program V5.
Human effective intestinal permeability was optimized by SimCYP program V13. Tolterodine
falls into class III (High permeability/Low fraction unbound to plasma proteins) and
hence was subjected to salivary excretion. A high pearsons correlation coefficient
of 0.97 between mean saliva and plasma concentrations, and saliva/plasma concentrations
ratio of 0.33 were observed. In addition, correlation coefficients and saliva/plasma
ratios of area under curve and maximum concentration were 0.98, 0.95 and 0.42, 0.34
respectively. On the other hand, time to reach maximum concentration was higher in
saliva by 2.37 fold. In addition, inter subject variability values in saliva were
slightly higher than plasma leading to need for slightly higher number of subjects
to be used in saliva studies (55 vs. 48 subjects). Non-invasive saliva sampling instead
of invasive plasma sampling method can be used as a surrogate for bioavailability
and bioequivalence of SECS class I drugs when adequate sample size is used.
Key words
SECS - tolterodine - bioequivalence - pharmacokinetics - simCYP
