Pharmacokinetics of oxytetracyline in Arctic charr

Ž . Ž The pharmacokinetics of oxytetracycline OTC was studied in Arctic charr SalÕelinus alpinus . Ž . L. in freshwater at a mean water temperature of 6.38C, after intravascular i.v.; 10 and 20 mgrkg Ž . and oral p.o.; 50 and 100 mgrkg administration. Two different oral formulations were tested as carriers for OTC; one in which OTC was dissolved in agar, the other where OTC was encapsulated in liposomeralginate particles. Blood samples were collected via a cannula placed in the dorsal aorta, and the concentration of OTC in plasma was assayed using solid phase extraction Ž . Ž . SPE and high-performance liquid chromatography HPLC . Pharmacokinetic analysis of plasma concentration–time data after i.v. administration indicated that a three-compartment model best Ž . described OTC disposition in Arctic charr. The volume of distribution V and total body dŽarea. Ž . y1 y1 clearance Cl ranged from 2.57 to 2.90 lrkg and from 6.27 to 6.54 ml kg h , respectively. T Ž . The elimination of OTC after i.v. administration was relatively slow; the half-lives t were 1r2 266.3 and 326.9 h in fish receiving 10 and 20 mg OTCrkg, respectively. No dose-dependent pharmacokinetics could be observed. The absorption of OTC was incomplete for both formulaŽ . tions tested. The mean bioavailability F of OTC ranged from 3.2% to 7.3%. Dose and drug formulation had, however, no significant effect on the bioavailability. The mean maximum Ž . concentration of OTC in plasma C was significantly higher in the group receiving OTC in max Ž . Ž . agar 3.93 mgrml compared to the liposomeralginate group 0.97 mgrml . The mean time to Ž . reach C T was also significantly longer in fish receiving the liposomeralginate formulamax max Ž . Ž . tion 136.0 h compared to fish receiving the agar formulation 17.8 h . Results from the present ) Corresponding author. Tel.: q47-77-64-60-71; fax: q47-77-64-60-20. Ž . E-mail address: [email protected] T. Haug . 0044-8486r00r$ see front matter q 2000 Elsevier Science B.V. All rights reserved. Ž . PII: S0044-8486 99 00376-2 ( ) T. Haug, P.A. HalsrAquaculture 186 2000 175–191 176 study indicate that liposomeralginate particles show little promise as a drug carrier for OTC in oral formulations to fish since it did not increase the bioavailability of the drug. q 2000 Elsevier Science B.V. All rights reserved.