Pharmacokinetics, bioavailability and withdrawal period of antibiotic oxytetracycline in catfish Pangasianodon hypophthalmus

• Published in: Environmental toxicology and pharmacology Vol. 89; p. 103778
• Main Authors: Manna, Sanjib Kumar, Das, Nilemesh, Sarkar, Dhruba Jyoti, Bera, Asit Kumar, Baitha, Raju, Nag, Subir Kumar, Das, Basanta Kumar, Kumar, Ashok, Ravindran, Rajisha, Krishna, Nanitha, Patil, Prasanna Kumar
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2022; Elsevier Science Ltd
• Subjects: Administration, Oral; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Antibiotics; Aquaculture - methods; Bacterial diseases; Bioavailability; Biological Availability; Blood circulation; Blood levels; Catfish; Catfishes; Dose-Response Relationship, Drug; Drug withdrawal; Food Contamination - prevention & control; Kidneys; Liver; Microbial Sensitivity Tests; Oral; Oral administration; Oxytetracycline; Oxytetracycline - administration & dosage; Oxytetracycline - analysis; Oxytetracycline - pharmacokinetics; Pangasianodon hypophthalmus; Pangasius; Parenteral; Pharmacokinetics; Pharmacology; Shellfish; Tetracycline; Pangasius; Oral; Pharmacokinetics; Parenteral; Tetracycline
• ISSN: 1382-6689; 1872-7077
• DOI: 10.1016/j.etap.2021.103778

The antibiotic oxytetracycline (OTC) has been widely used for therapeutic and preventive management of bacterial diseases in finfish and shellfish. In the present study the bioavailability, pharmacokinetics, and withdrawal period of the OTC have been determined following in-feed administration in intensively cultured catfish Pangasianodon hypophthalmus. Furthermore, the pharmacokinetic parameters of oral route were also compared with parenteral route. Drug concentrations were measured in various tissues at different time intervals by LC-MS/MS. The study revealed the drug kinetics best followed the enterohepatic circulation model with very poor bioavailability and low blood concentration after oral administration. In the withdrawal study, after 10-days of in-feed administration at the therapeutic dose the drug reached very high concentrations in the liver and kidneys but did not attain minimum inhibitory concentrations (MICs) in blood or flesh. OTC concentration also did not exceed the recommended MRL value in flesh; however, considering high amounts of the chemical in the liver and kidneys a withdrawal period of 4 days (at 28 ± 1.5 oC) is recommended for consumer safety. Poor bioavailability and non-attainment of minimum therapeutic concentration in blood and flesh do not warrant in-feed administration of OTC for control of bacterial diseases in P. hypophthalmus. All data generated and analyzed during this study are included in this article. Raw data may be shared upon reasonable request. •Pharmacokinetics and withdrawal period of oxytetracycline (OTC) were studied in aquaculturally important P. hypophthalmus.•The drug kinetics followed enterohepatic circulation model with poor bioavailability after in-feed administration.•Bulk hepatic transport and excretion had led to OTC concentration below MIC in blood.•Although OTC level was below MRL in flesh, 4 days withdrawal period is recommended for full consumer safety.•Low bioavailability and blood levels do not suggest in-feed administration of OTC for disease control in Pangasius.