This Phd thesis presents an extensive investigation of the kinetic behaviour of oxolinic acid (OA) and oxytetracycline (OTC) in Gilthead Sea Bream (GSB) (“Sparus aurata” L.) and Sharpsnout Sea Bream (SSB) (“Diplodus puntazzo” Cetti, 1777) at 19-20[sup]oC. The distribution half-life (t[sub]1/2[alpha]) and the elimination half-life (t[sub]/2[beta]) of OA from GSB plasma were found to be short (0.5 and 12h respectively) while longer values were estimated for OTC (2 and 53h respectively). Similarly, in SSB, calculated t[sub]1/2[alpha] and t[sub]1/2[beta] revealed values of 0.4 and 10h, respectively. The corresponding values for OTC were 1.4 and 34h. The apparent volume of distribution at steady-state (V[sub]d(ss)) of OA was identical in the two species (2Ikg[sup]-1). Higher V[sub]d(ss) values of OTC were found in both sparids (2.9 and 4lkg[sup]-1 for GSB and SSB, respectively).
The bioavailabilities (F%) of OA and OTC following oral administration were found to be low in GSB (14 and 9% respectively). In SSB, the F of OA was calculated to be 15% while absorption of OTC was totally inhibited. The apparent digestibility of OTC was determined to be 27% in GSB and 40% SSB. However, the apparent digestibility of OA in both fish was considerably higher (92%; GSB, 88%; SSB). The tissue distribution and residue depletion of OA in both sparids revealed that OA is eliminated from edible tissues rapidly, allowing short withdrawal times.
Short and long withdrawal times for OA and OTC respectively, are shown in this work to be necessary for safe human consumption of treated fish. All experiments in this work indicated reduced absorption of both drugs, which would result in significant release of the drugs in the vicinity of aquatic farms using sparids. This poses an environmental concern because of the potentially rapid development of a resistant aquatic bacterial population and possible adverse effects for other organisms in the habitat. Also there are potential financial losses associated with drug losses to the environment. Therefore, low drug absorption is clearly undesirable and studies to improve their absorption in sparids for future therapies is of vital importance