Population pharmacokinetics, in-feed bioavailability and tissue depletion of imidazole antifungal clotrimazole in Pangasianodon hypophthalmus.

Fungal enzootics and epizootics cause significant biological loss in fisheries and aquaculture necessitating and sometimes forcing non-legal use of veterinary medicinal products sans essential scientific data on drug efficacy, kinetics, residue levels, etc. The present study determines the pharmacokinetics, bioavailability and tissue depletion of clotrimazole (CTZ), one of the oldest and most effective azoles against a major fungal pathogen Saprolegnia parasitica, following enteral and parenteral administrations in widely consumed catfish Pangasianodon hypophthalmus. The drug residues in fish tissues at different time points were quantified by LC-MS/MS. The results showed very slow kinetics including absorption/distribution, and elimination of CTZ, especially after parenteral administration. Following bolus oral administration, the drug underwent first pass with negligible clearance from liver, and very high residence time in all the tissues. However, high AUC/MIC ratio, Cmax> MIC and prolong %T > MIC value in blood predicted clinical efficacy of the azole. Relative oral bioavailability of CTZ, estimated by different pharmacokinetic models, ranged between 152.59% and 183.4% in the catfish. The depletion times of CTZ from fish flesh following 7-days in-feed administration were determined to be 1296, 1242, 864 degree-days for residue concentrations of 50 µg kg− 1, 100 µg kg− 1 and 200 µg kg− 1, respectively. The data generated would be instrumental in determining any future use of CTZ for controlling fungal diseases in finfish. Dire need of the aquaculture sector for effective antifungals vis-a-vis consumer health risks from use of azoles in food fish are discussed.