Abstract
Aims:
To study saliva and plasma bioequivalence of paracetamol in healthy human volunteers,
and to investigate the robustness of using saliva instead of plasma as surrogate for
bioequivalence of class I drugs according to the salivary excretion classification
system (SECS).
Methods:
Saliva and plasma pharmacokinetic parameters were calculated by non compartmental
analysis. Analysis of variance, 90% confidence intervals, intra-subject and inter-subject
variability values of pharmacokinetic parameters were calculated after logarithmic
transformation. Calculations were done using Kinetica program V5. Descriptive and
comparative statistics were also calculated by Excel.
Results and Discussion:
Paracetamol falls into class I (High permeability/High fraction unbound to plasma
proteins) and was subjected to salivary excretion, with correlation coefficient of
0.99 between saliva and plasma concentrations and saliva/plasma concentrations ratios
of 1.45–1.50. The 90% confidence limits of areas under curve (AUClast and AUC∞) showed similar trend and passed the 80–125% acceptance criteria in both saliva and
plasma. On the other hand for maximum concentration (Cmax), the 90% confidence limits passed the acceptance criteria in plasma and failed in
saliva. Inter and intra subject variability values in saliva were higher than plasma
leading to need for higher number of subjects to be used in saliva. Saliva and plasma
parameter ratios were not significantly different (P>0.05).
Conclusions:
Saliva instead of plasma can be used as surrogate for bioequivalence of class I drugs
according to SECS when adequate sample size is used. Future work is planned to demonstrate
SECS robustness in drugs that fall into classes II or III.
Key words
salivary excretion classification system - paracetamol - bioequivalence - pharmacokinetics
- simCYP
