Oxytetracycline Pharmacokinetics in Rainbow Trout during and after an Orally Administered Medicated Feed Regimen

Abstract

The pharmacokinetic-pharmacodynamic predictor of antimicrobial activity for tetracyclines is reported to be the area under the concentration-time curve at steady state (AUC(ss)) divided by the minimal inhibitory concentration of the targeted pathogen. Here, we estimate AUC(ss) values for oxytetracycline (OTC) in serum of rainbow trout Oncorhynchus mykiss by using a destructive sampling study design. Seventy-two rainbow trout were fed OTC-medicated feed at 74.7 +/- 1.5 mg/kg (mean +/- SD) body weight (BW) by oral gavage for 10 consecutive days. Serum was collected from nine fish at 1, 3, 6, 8, 10, 12, 15, and 22 d after dosing began. Serum OTC concentrations were measured by high-performance liquid chromatography with a 0.01-microg/mL limit of detection. The average OTC AUC(ss) was 29.2 microg x h/mL and was estimated using nonlinear mixed-effects modeling and bootstrap resampling techniques. The elimination half-life was estimated as 85.0 h, and the fraction of steady state achieved was estimated as 0.85. The calculated AUC(ss) (24.8 microg x h/mL) following 10 d of oral dosing with 75 mg OTC/kg BW was less than the estimated AUC(ss). Results suggest that the pharmacokinetics of OTC exposure, including the AUC(ss), is better evaluated by using multiday dosimetry than by using a standard single-dose protocol.

A critical approach on pharmacokinetics, pharmacodynamics, dose optimisation and withdrawal times of oxytetracycline in aquaculture

“…Studies that employ oral intubation can, however, provide little information on interfish variation that might be expected under commercial farming conditions, because the primary aim of these studies is to deliver identical doses across test populations (Miller et al . ).…”

“…For instance, SO administration of 75 mg kg À1 fish as an alcohol solution through stomach intubation at 5-16°C resulted in much higher C max serum values with the maximum concentration (2.1-5.3 mg L À1 ) measured at 10°C (Bjorklund & Bylund 1990). Miller et al (2012) showed that delivery of 75 mg kg À1 via gavage on 10 consecutive days resulted in a AUC ss of 29.2 mg h L À1 in rainbow trout kept at 12°C. Moreover, the F of OTC administered in a gelatin capsule (50 mg kg À1 ), containing a methanolic solution and forced into the stomach using a glass rod, was estimated to be 30.3%, while C max and AUC 0-∞ in blood reached 5.8 mg L À1 and 2884 mg h L À1 , respectively, in cannulated fish kept at 11°C .…”

“…Miller et al . () showed that delivery of 75 mg kg −1 via gavage on 10 consecutive days resulted in a AUC ss of 29.2 mg h L −1 in rainbow trout kept at 12°C. Moreover, the F of OTC administered in a gelatin capsule (50 mg kg −1 ), containing a methanolic solution and forced into the stomach using a glass rod, was estimated to be 30.3%, while C max and AUC 0–∞ in blood reached 5.8 mg L −1 and 2884 mg h L −1 , respectively, in cannulated fish kept at 11°C (Abedini et al .…”

“…Miller et al . () have recently proposed that AUC ss, the area under the concentration–time curve at steady state, might be an alternative to AUC 0–24 .…”

“…One paper, Miller et al . (), did report a value for AUC ss . They argued that this parameter deserved consideration as an appropriate PK/PD index.…”