Effect of dose escalation on multiple dose pharmacokinetics of orally administered praziquantel in kingfish Seriola lalandi

Oral praziquantel (PZQ) preparations, administered using multiple dosing regimens, have recently been investigated for the treatment of monogenean parasites of Seriola species cultured in sea-cages. To evaluate existing dosing regimens, the pharmacokinetics of two oral PZQ doses, 50 mg kg− 1 body weight (BW) and 150 mg kg− 1 BW, administered every 24 h for 8 days and 3 days respectively were compared in the plasma and skin of kingfish Seriola lalandi using HPLC. In the skin of kingfish, significantly higher maximum tissue PZQ concentrations (Cmax) were achieved with a 150 mg kg− 1 PZQ dose, but no difference in plasma Cmax occurred between the two doses. The higher dose resulted in, on average, 2.4 fold higher PZQ concentrations in skin than the lower dose. Although no difference was found between the residual PZQ concentrations (Cmin) of either dose measured prior to dosing each day, there were significant differences in this parameter between days of drug administration. Praziquantel Cmin varied significantly in kingfish skin regardless of dose, but similar differences were only found at the lower dose in plasma. A non-linear relationship between tissue drug concentration and dosage indicated potential saturation of active absorption mechanisms; a 3-fold increase in the administered dose only led to an average 1.5 fold increase in plasma and 2.4 fold increase in skin PZQ concentrations over the three days the doses could be compared. Concentrations of the drug in the skin of kingfish were found to be 40–50% of that in plasma and the drug appeared not to accumulate significantly in either tissue over the administration period. These initial studies indicate that under existing oral dosing regimens, using a fixed 24 h dosing interval, parasites will be exposed to similar and highly variable anthelmintic concentrations on a daily basis, which may be sub-optimal for the treatment of monogeneans in this finfish species.