H. Quiding et al., Saliva-resistant coating of tablets prevents oral release of penicillin - Plasma but not saliva equivalence, EUR J CL PH, 54(9-10), 1998, pp. 749-752
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.