Title

Pharmacokinetics of Tetracycline Antibiotic Distribution In Penaeid Shrimp

Date of Award

1991

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry and Biochemistry

First Advisor

Kenneth McMurtrey

Advisor Department

Chemistry and Biochemistry

Abstract

This dissertation reports on metabolism and pharmacokinetics of Tetracycline Antibiotics; primarily Tetracycline (TC) and Oxytetracycline (OTC), in P. aztecus in vitro and in vivo under aquaculture conditions. The extraction of tetracycline antibiotics from aqueous media using bonded phase cartridge isolation, and the use of HPLC with combined electrochemical and ultraviolet detection to monitor tetracyclines in shrimp is described. The 9,000 X G supernatant (S-9) fractions from shrimp hepatopancreas were incubated with TC or OTC under conditions designed to maximize cytochrome P-450 oxidase activity (NADPH, O$\sb2).$ Evidence for the in vitro metabolism of TC and OTC in Penaeus aztecus (brown shrimp) was not seen. A two compartment pharmacokinetic model with first order drug absorption was proposed for OTC disposition in Penaeus aztecus, and microscopic rate constants calculated from experimental data. To test the kinetic model, computer simulation of the two compartment model was performed using SIMKIN, a computer program written for this purpose. This research was supported by a grant from the Institute of General Medical Sciences of the NIH, No. R15 GM38704.