Saliva-resistant coating of tablets prevents oral release of penicillin - Plasma but not saliva equivalence

Objective: To investigate saliva and plasma concentrations of penicillin af ter the intake of a conventional phenoxymethylpenicillin (PcV) tablet and a tablet with saliva-resistant coating (PcVsr), both containing Ig penicilli n. Methods: The study had an open randomized crossover design and involved 24 healthy subjects. Saliva and blood were sampled intermittently for 6 h afte r tablet intake. Results: Within the first 10 min after tablet intake penicillin was detecte d in saliva in ten subjects taking PcV and in none taking PcVsr (P < 0.001) . These initial saliva concentrations were short-lasting, but in some subje cts 50 to 100 times higher than those following the peak concentration in p lasma, i.e. at 40 min or more after swallowing. From 40 min and onwards the saliva concentrations of penicillin were very similar for the two formulat ions. The elimination of high initial saliva concentrations may diminish ec ological disturbances of the mouth flora as well as removing the unpleasant taste of penicillin. The plasma concentrations of penicillin were similar for the two formulations throughout the 6-h sampling period and the mean ra tio of the area under the plasma concentration-time curve was 99% for PcVsr in relation to PcV, the 90% confidence interval being 86-115%. The corresp onding values for the maximum plasma concentration were 108% and 93-127%. T he time to maximum concentration was 45 min for PcVsr and 41 min for PcV. T hus, with regard to standard criteria which are based on systemic (plasma) concentrations, the formulations were bioequivalent despite the substantial difference in initial local (saliva) concentrations. Conclusion: Saliva-resistant coating of tablets can prevent oral release of penicillin without affecting the plasma concentrations. From a clinical po int of view both local and systemic equivalence should be established befor e bioequivalence is assumed.