Pharmacokinetics, tissue distribution and metabolism of acriflavine and proflavine in the channel catfish (Ictalurus punctatus)

S. M. PLAKAS Gulf Coast Seafood Laboratory, US Food and Drug Administration, PO Box 158, Dauphin Island, AL 36528, USA OE Instrumentation and Biophysics Branch, US Food and Drug Administrat ion, 200 C St SW, Washington, DC 20204, USA The Ohio State University, College of Pharmacy, 500 West Twelfth Avenue, Columbus, OH 43210, USA

K. R. EL SAID Gulf Coast Seafood Laboratory, US Food and Drug Administration, PO Box 158, Dauphin Island, AL 36528, USA OE Instrumentation and Biophysics Branch, US Food and Drug Administrat ion, 200 C St SW, Washington, DC 20204, USA The Ohio State University, College of Pharmacy, 500 West Twelfth Avenue, Columbus, OH 43210, USA

F. A. BENCSATH Gulf Coast Seafood Laboratory, US Food and Drug Administration, PO Box 158, Dauphin Island, AL 36528, USA OE Instrumentation and Biophysics Branch, US Food and Drug Administrat ion, 200 C St SW, Washington, DC 20204, USA The Ohio State University, College of Pharmacy, 500 West Twelfth Avenue, Columbus, OH 43210, USA

S. M. MUSSER Gulf Coast Seafood Laboratory, US Food and Drug Administration, PO Box 158, Dauphin Island, AL 36528, USA OE Instrumentation and Biophysics Branch, US Food and Drug Administrat ion, 200 C St SW, Washington, DC 20204, USA The Ohio State University, College of Pharmacy, 500 West Twelfth Avenue, Columbus, OH 43210, USA

W. L. HAYTON Gulf Coast Seafood Laboratory, US Food and Drug Administration, PO Box 158, Dauphin Island, AL 36528, USA OE Instrumentation and Biophysics Branch, US Food and Drug Administrat ion, 200 C St SW, Washington, DC 20204, USA The Ohio State University, College of Pharmacy, 500 West Twelfth Avenue, Columbus, OH 43210, USA

Abstract

1. The disposition of proflavine (PRO) and acriflavine (ACR) were examined in channel catfish after intravascular (i.v.) dosing (1 mg/kg) or waterborne exposure (10 mg/l for 4 h). 2. After i.v. dosing, plasma concentration-time profiles of parent PRO and ACR were best described by two- and three-compartment pharmacokinetic models respectively. Terminal elimination half-lives of PRO and ACR in plasma were 8.7 and 11.4 h respectively. 3. In animals dosed with ¹⁴C-PRO or ¹⁴C-ACR, total drug equivalent concentrations were highest in the excretory organs and lowest in muscle, fat and plasma. In PRO-dosed animals, residues in the liver and trunk kidney were composed primarily of glucuronosyl and acetyl conjugates of PRO; residues in muscle were composed mostly (> 95%) of the parent drug. In ACR-dosed animals, the parent compound comprised > 90% of the total residues in all tissues examined. 4. PRO and ACR were poorly absorbed in catfish during waterborne exposure. At the end of a 4-h exposure, parent PRO and ACR concentrations in muscle were 0.064 and 0.020 μg/g respectively. Levels in muscle declined below the limit of determination (0.005 μg/g) within 1-2 weeks.

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Pharmacokinetics, tissue distribution and metabolism of acriflavine and proflavine in the channel catfish (Ictalurus punctatus)

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Pharmacokinetics, tissue distribution and metabolism of acriflavine and proflavine in the channel catfish (Ictalurus punctatus)

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