REPEATED DOSE PHARMACOKINETICS OF PANCOPRIDE IN HUMAN VOLUNTEERS

The aim of this study was to assess the pharmacokinetic profile of pancopride after repeated oral dose administration of 20 mg pancopride in tablet form once a day for 5 d in 12 healthy male volunteers. Plasma levels were measured by HPLC using a solid phase extraction method and automated injection. The minimum quantification limit of pancopride in plasma was 2 ng mL(-1). The maximum plasma concentration (mean+/-SD) after the first dose was 92.5+/-41.5 ng mL(-1) and t(max) was 1.7+/-0.9 h. The elimination half-life (t(1/2)) was 14.3+/-6.9 h. The area under the concentration-time curve from zero to infinity (AUC) was 997+/-396 ng h mL(-1). The maximum plasma concentration (mean+/-SD) at steady state (day 5) was 101.8+/-36.9 ng mL(-1) and t(max) was 2.2+/-1.2 h. The elimination half-life (t(1/2)) was 16.3+/-2.7 h and the minimum plasma concentration (C-min(ss) was 16.6+/-6.9 ng mL(-1). The area under the concentration-time curve during the dosing interval (AUC(r)(ss)) was 995+/-389 ng h mL(-1). The average plasma concentration at steady state (C-av(ss)) was 43.3+/-16.1 ng mL(-1) and the experimental accumulation ratio (R(AUC)) was 1.34+/-0.19, whereas the mean theoretical value (R) was 1.40+/-0.29. The results obtained showed a good correlation between the experimental plasma levels and the expected values calculated using a repeated dose two-compartment model assessed by means of the Akaike value. It is concluded that the pharmacokinetics of pancopride are not modified after repeated dose administration. The safety parameters showed no clinically relevant alterations.