Plasma and Tissue Depletion of Oxolinic Acid after Administration to Orange-Spotted Grouper (Epinephelus coioides), Snubnose Pompano (Trachinotus blochii) and Giant Seaperch (Lates calcarifer)

Abstract

Pharmacokinetics and residues of oxolinic acid (OXO) in serum, muscle, liver, and kidney were measured in orange-spotted grouper Epinephelus coioides, snubnose pompano Trachinotus blochii and giant seaperch Lates calcarifer. Fish were treated with OXO after a single-dose trial (60 mg/kg) by oral gavages and repeat-doses of 60 mg/kg of body weight once daily in feed for five consecutive days. Analysis of OXO kinetic profiles, when determined by HPLC provided elimination half-life in muscle were 131, 26, and 85 h for 26-27 °C orange-spotted grouper, snubnose pompano, and giant seaperch, respectively. Depletion studies were conducted the time for OXO concentrations to fall below 0.1 µg/g (the current tolerance set by the European Medicines Agency (EMA) among fish species establishing an adequate depletion period). The mean tissue OXO concentration in the edible portion was below maximum residue level (MRL) of snubnose pompano at 6 d postdosing, for orange-spotted grouper and giant seaperch, at 10 d postdosing, respectively. When possible, depletion data were fitted to a one-compartment pharmacokinetic model. For all test species, the longest withdrawal period of 9 days in snubnose pompano and 15 days in orange-spotted grouper and giant seaperch were calculated because of a safety span (corresponds to 50% of the time point when at which residues fall below the MRL added to the depletion time). These results suggest withdrawal times with reference to human consumption of treated fish, to establish policy guidelines and basic principles regarding the use of OXO for fish-farming, and to fish-farmers for the proper handling to ensure safe fish that the consumer will not be at risk.

Accumulation and depletion of oxytetracycline (OTC) and oxolinic acid (OXA) in Pompano, Trachinotus blochii

“…This is also the reason for the limited data point to allow computation of the withdrawal period. The observed depletion of OXA in pompano even during the time they are receiving 30mg/kg of OXA is contrary to the observation of Chen et al (2021).…”

“…OXA accumulation and depletion in pompano observed in this study is consistent with the activity of OXA in sharpsnout sea bream wherein a rapid distribution and elimination, moderate tissue penetration, and low absorption of the drug was reported (Rigos et al 2003). The observed OXA concentration in the depletion study in pompano muscle in this study is comparable to the observation of Chen et al (2021) given a higher dose of OXA at 60mg/kg/day for 5 days.…”

“…The regression equation obtained from the plotted OXA concentration vs. time has a coefficient (R 2 ) of 0.7 and 0.8668 in the muscle and blood, respectively. These are comparable to the results of Chen et al (2021) who reported regression coefficients of 0.85 and 0.83 for OXA in pompano muscle and blood, respectively. The computed withdrawal period of 3 days at 30 o C or 90 degree days for OXA in the Pompano muscle and blood is shorter than the 9 days at 26-27 o C reported by Chen et al (2021) in the same fish.…”

“…The regression equation obtained from the plotted OTC concentration vs. time has a coefficient (R 2 ) of 0.8 both for muscle and blood samples. Regression coefficient of 0.8 and below are reported in OXA withdrawal studies in the muscle of orange-spotted grouper (0.79) and in the serum of giant sea perch (0.62) (Chen et al 2021). The obtained R 2 of 0.8 both for muscle and blood samples allowed the use of the regression equation derived from the curve fitting to compute for the withdrawal period of OTC in pompano.…”

“…The withdrawal period for tilapia (Orechromis niloticus) cultured in Brazil was determined to be 6 days (Paschoal et al 2011). A withdrawal period of 9 days was observed in pompano (Trachinotus blochii) given a single dose of 60mg/kg cultured at 26-27 o C; 15 days in orange-spotted grouper (Epinephelus coioides) and seaperch (Lates calcarifer) (Chen et al 2021). Withdrawal period of OXA and OTC in Trachinotus cultured at 30 o C has not yet been reported.…”