Efficacy, tissue distribution, and residue depletion of oxytetracycline in WS-RLP infected California red abalone Haliotis rufescens

Oxytetracycline (OTC) was recently demonstrated to be an effective therapeutant for California red abalone (Haliotis rufescens) infected with the agent of withering syndrome (WS), a Rickettsia-like prokaryote (WS-RLP). This study examined the influence of temperature on the efficacy and pharmacokinetics of oral OTC treatments on WS-RLP infected red abalone, H. rufescens. Medication was administered in an artificial diet containing 1.85% active OTC at a rate of 103.4 mg/kg abalone for 10, 20 and 30 days at both 13.4 C and 17.3 degrees C. Drug residue concentrations, WS-RLP burden and WS-associated pathological changes within foot muscle and digestive gland were measured 3,17, 23, 42, 63, 81,102,122, and 160 days after OTC treatment. In all samples the highest concentrations of OTC were detected on the first sample day. Furthermore, all sampling periods showed significantly less OTC in foot muscle samples relative to corresponding digestive gland samples (p<0.001). While drug deputation occurred rapidly from foot muscle, unusually high concentrations and long deputation times were measured within the digestive gland. The pharmacokinetic trends in both the foot muscle and digestive gland at 13.4 C were adequately described by a one-compartment model, while the digestive gland deputation models within the 17.3 degrees C treatments conformed to a two-compartment model. At both temperatures treatment duration gave rise to significant differences in OTC accumulation and depletion (p<0.001). Despite this, terminal elimination rate constants were similar. Estimated half-lives were similar among all treatments for digestive gland (23.8-27.5 d) and all treatments for the foot muscle at 13.4 degrees C (10.7-13.4 d; calculated only for the 13.4 degrees C treatments). At both temperatures all three durations of drug treatment led to significant reductions in WS-RLP prevalence, foot muscle atrophy, and mortality. WS-RLP re-challenge trials initiated 44, 88, and 122 days following the 10-day treatment at 17.3 degrees C showed reduced susceptibility to re-infection for up to 88 days after treatment, suggesting that digestive gland OTC residues confer long-term resistance to pathogen. Atomic absorption spectroscopy conducted on both foot muscle and digestive gland found significantly higher concentrations of iron, zinc, and manganese in the digestive gland, offering an explanation behind the underlying mechanism of OTC retention for extended periods within this tissue. (C) 2008 Elsevier B.V. All rights reserved.