Journal of fish pathology (한국어병학회지)

The Korean Society of Fish Pathology (한국어병학회)
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Pharmacokinetics of cefadroxil after oral administration in olive flounder, Paralichthys olivaceus

Cefadroxil의 경구투여에 따른 넙치(Paralichthys olivaceus)에서의 약물동태학 연구

  • Lee, Ji-Hoon (Department of Aquatic Life Medicine, College of Ocean Science and Technology, Kunsan National University) ;
  • Park, Kwan Ha (Department of Aquatic Life Medicine, College of Ocean Science and Technology, Kunsan National University)
  • 이지훈 (군산대학교 수산생명의학과) ;
  • 박관하 (군산대학교 수산생명의학과)
  • Received : 2018.05.25
  • Accepted : 2018.06.11
  • Published : 2018.06.30
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Abstract

The pharmacokinetic properties of cefadroxil (CDX) were studied after oral administration for 7 days to cultured olive flounders (average 660 g), Paralichthys olivaceus. For examination of pharmaco-kinetic profiles, CDX of 45 to 225 mg/kg body weight was administered at two different water temperatures, $13{\pm}3^{\circ}C$ or $22{\pm}3^{\circ}C$. CDX concentrations were determined in muscle, plasma, gastrointestinal tract, hematopoietic organs and liver by HPLC-MS/MS. Muscle samples were taken at 0.25, 0.5, 1, 3, 7, 14 and 28 days post dose, whereas plasma, gastrointestinal tract, hematopoietic organs and liver concentrations were measured at 1, 3, 7, 14 and 28 days post-dosing. The kinetic profiles of $C_{max}$, $T_{max}$, $T_{1/2}$ of CDX were analyzed by fitting to a non-compartmental model with PKSolver program. The following pharmacokinetic parameters were obtained with oral administration of 45 and 225 mg/kg at 13 and $22^{\circ}C$ in muscle, plasma, gastrointestinal tract, hematopoietic organs and liver, respectively: $C_{max}$ (maximum tissue concentration)=$985.98-5,032.86{\mu}g/kg$, $5,670.99-38,922.23{\mu}g/l$, $2,457.27-10,192.78{\mu}g/kg$, $886.04-3,070.87{\mu}g/kg$ and $1,188.15-3,814.33{\mu}g/kg$; $T_{max}$ (time for maximum concentration)= every 1 day; $MRT_{0-{\infty}}$ (mean residence time)= 1.51-4.74, 2.12-3.06, 4.25-13.18, 1.37-18.66 and 1.78-29.76 days; $T_{1/2}$ (half-life)= 1.08-3.47, 1.14-5.42, 3.56-10.99, 1.17-14.93 and 1.25-28.55 days.

세파드록실 (CDX)의 수온에 따른 잔류 약동학적 특성을 알아보기 위해 평균 660 g의 넙치를 비교수온 ($13{\pm}3^{\circ}C$) 및 적정수온 ($22{\pm}3^{\circ}C$)에서 7일간 임상용량 (45 mg/kg b.w.)과 임상용량의 5배에 해당하는 양 (225 mg/kg b.w.)으로 연속 경구투여 후 시간에 따른 근육, 혈장, 위-장관, 조혈조직 (신장+비장) 및 간장에서 잔류농도를 HPLC-MS/MS로 분석하였다. CDX의 농도 측정을 위해 근육에서는 투여종료 후 0.25, 0.5, 1, 3, 7, 14 및 28일에 분석하였고, 혈장, 위-장관, 조혈조직 및 간장에서는 1, 3, 7, 14 및 28일에 분석하였다. 경시적 잔류농도를 바탕으로 PKSolver program의 non-compartmental model로 최고농도 ($C_{max}$), 최고농도 도달시간 ($T_{max}$), 배설반감기 ($T_{1/2}$) 등의 약물동태학적 매개변수(parameter)를 계산하였다. 근육, 혈장, 위-장관, 조혈조직 및 간장에서 최고농도 및 최고농도 도달시간은 각각 $985.98-5,032.86{\mu}g/kg$ (1일), $5,670.99-38,922.23{\mu}g/l$ (1일), $2,457.27-10,192.78{\mu}g/kg$ (1일), $886.04-3,070.87{\mu}g/kg$ (1일) 및 $1,188.15-3,814.33{\mu}g/kg$ (1일)으로 계산되었다. 평균체류시간 ($MRT_{0-{\infty}}$)과 배설반감기 ($T_{1/2}$)는 각각 1.51-4.74일 (1.08-3.47일), 2.12-3.06 (1.14-5.42일), 4.25-13.18일 (3.56-10.99일), 1.37-18.66일 (1.17-14.93일) 및 1.78-29.76일 (1.25-28.55일)로 계산되었다.

Keywords

References

  1. Alimentarius C.: CAC/GL 71-2009. Guidelines for the design and implementation of national regulatory food safety assurance programme associated with the use of veterinary drugs in food producing animals. Rome: Codex Secretariat. Adopted., 2009.
  2. Barbhaiya RH.: A pharmacokinetic comparison of cefadroxil and cephalexin after administration of 250, 500 and 1000 mg solution doses. Biopharm. Drug Dispos. 17: 319-330, 1996. https://doi.org/10.1002/(SICI)1099-081X(199605)17:4<319::AID-BDD957>3.0.CO;2-W
  3. Bjorklund H and Bylund G.: Temperature-related absorption and excretion of oxytetracycline in rainbow trout (Salmo gairdneri R.). Aquacult. 84: 363-372, 1990. https://doi.org/10.1016/0044-8486(90)90101-R
  4. Colin P, De Bock L, T'jollyn H, Boussery K and Van Bocxlaer J.: Development and validation of a fast and uniform approach to quantify ${\beta}$-lactam antibiotics in human plasma by solid phase extractionliquid chromatography-electrospray-tandem mass spectrometry. Talanta. 103: 285-293, 2013. https://doi.org/10.1016/j.talanta.2012.10.046
  5. Cutler RE, Blair AD and Kelly MR.: Cefadroxil kinetics in patients with renal insufficiency. C. Pharmacol. Therap. 25: 514-521, 1979. https://doi.org/10.1002/cpt1979255part1514
  6. Duffee NE, Christensen JM and Craig AM.: The pharmacokinetics of cefadroxil in the foal. J. vet. Pharmacol. Therap. 12: 322-326, 1989. https://doi.org/10.1111/j.1365-2885.1989.tb00678.x
  7. Duffee NE, Stang BE and Schaeffer DJ.: The pharmacokinetics of cefadroxil over a range of oral doses and animal ages in the foal. J. vet. Pharmacol. Therap. 20: 427-433, 1997. https://doi.org/10.1046/j.1365-2885.1997.00085.x
  8. Fan GR, Li Z, Tang SX, Shi J, Song HJ, Liu T and Hu JH.: Pharmacokinetics and relative bioavailability of cefadroxil dispersible tablet in healthy volunteers. Acad. J. of Sec. Mil. Med. Univ. 4: 19, 2002.
  9. Garcia-Carbonell MC, Granero LUIS, Torres-Molina FRANCISCA, Aristorena JC, Chesa-Jimenez J, Pla-Delfina JM and Peris-Ribera JE.: Nonlinear pharmacokinetics of cefadroxil in the rat. D. M. D. 21: 215-217, 1993.
  10. Hekman P.: Withdrawal-time Calculation Program. CVMP note of guidance: considerations on establishing withdrawal periods, 1996.
  11. Huh MJ and Myung SW.: Simultaneous analysis of ${\beta}$-lactam antibiotics in surface water. Anal. Sci. Technol. 23: 199-127, 2010.
  12. Jin HE, Kim IB, Kim YC, Cho KH and Maeng HJ.: Determination of cefadroxil in rat plasma and urine using LC-MS/MS and its application to pharmacokinetic and urinary excretion studies. J. of Chrom. B. 947: 103-110, 2014.
  13. Jung SH, Choi DL, Kim JW, Jo MR, Seo JS and Jee BY.: Pharmacokinetics of oxytetracycline in olive flounder (Paralichthys olivaceus) by dipping and oral administration. J. Fish Pathol. 21: 107-117, 2008.
  14. Jung SH, Seo JS, Jee BY, Kim JW and Park MA.: Effect of temperature on pharmacokinetics of nalidixic acid and piromidic acid in black rockfish Sebastes schlegeli following oral administration. J. Fish Pathol. 24: 29-37, 2011. https://doi.org/10.7847/jfp.2011.24.1.029
  15. Kano EK, Serra CHDR, Koono EEM, Fukuda K and Porta V.: An efficient HPLC-UV method for the quantitative determination of cefadroxil in human plasma and its application in pharmacokinetic studies. J. Liq. Chromatogr. Relat. Technol. 35: 1871-1881, 2012.
  16. Karageorgou E, Myridakis A, Stephanou EG and Samanidou V.: Multiresidue LC-MS/MS analysis of cephalosporins and quinolones in milk following ultrasound-assisted matrix solid-phase dispersive extraction combined with the quick, easy, cheap, effective, rugged, and safe methodology. J. Sep. Sci. 36: 2020-2027, 2013. https://doi.org/10.1002/jssc.201300194
  17. KFDA (Korean Food and Drug Administration): Advanced Notice No., pp. 9, Cheongju, 2017.
  18. Kim JS, Lee JH, Lee SJ and Park KH.: Pharmacokinetics of amoxicillin after intramuscular injection at different temperatures to cultured olive flounder, Paralichthys olivaceus. 28: 43-51, 2015.
  19. La Rosa, F., Ripa S, Prenna M, Ghezzi A and Pfeffer M.: Pharmacokinetics of cefadroxil after oral administration in humans. Antimicrob. Agents Chemother. 21: 320-322, 1982. https://doi.org/10.1128/AAC.21.2.320
  20. Marino EL, Dominguez-Gil AA, Cepeda M, Otero MJ and Dominguez-Gil A.: Effect of experimentally induced renal impairment on the pharmacokinetics of cefadroxil in rabbits. Arzneim. Forsc. 31: 478-481, 1981.
  21. NIFS: Guide Book for Aquacultural drug use, pp. 103, National Institute of Fisheries Science, Busan, 2016.
  22. Oh JH, Kwon CH, Jeon JS, and Choi DM.: Management of veterinary drug residues in food. Korean J. Environ. Agric. 28: 310-325, 2009. https://doi.org/10.5338/KJEA.2009.28.3.310
  23. Park MS, Lee JJ and Myung SW.: Analysis of phoxim residue in animal food production (cattle and pig) by LC/ESI-MS/MS. J. Korean Chem. Soc. 55: 626-632, 2011. https://doi.org/10.5012/jkcs.2011.55.4.626
  24. Rahim N, Naqvi S, Baqir S, Alam M, Rasheed A and Khalique UA.: Comparative bioavailability and pharmacokinetic study of Cefadroxil capsules in male healthy volunteers of Pakistan. Pakistan J. of pharmac. sci. 29, 2016.
  25. Son KT, Jo MR, Oh EG, Mok JS, Kwon JY, Lee TS, Song KC, Kim PH and Lee HJ.: Residues of Ampicillin and Amoxicillin in Olive Flounder Paralichthys olivaceus Following Oral Administration. Kor. J. Fish Aquat. Sci. 44: 464-469, 2011.
  26. Treves-Brown KM.: Applied Fish Pharmacology. Tetracyclines. pp. 64-82, Kluwer Academic Publishers, Boston, London, 2000.
  27. Welling PG, Selen A, Pearson JG, Kwok F, Rogge MC, Ifan A and Johnson CA.: A pharmacokinetic comparison of cephalexin and cefadroxil using HPLC assay procedures. Biopharm. Drug Dispos. 6: 147-157, 1985. https://doi.org/10.1002/bdd.2510060206
  28. Wilson WD, Baggot JD, Adamson PJ, Hirsh DC and Hietala SK.: Cefadroxil in the horse: pharmacokinetics and in vitro antibacterial activity. J. vet. Pharmacol. Therap. 8: 246-253, 1985. https://doi.org/10.1111/j.1365-2885.1985.tb00953.x
  29. Yoo HJ, Choi MK, Kim KS, Chung SJ and Shim CK.: Bioequivalence of Shinil Cefadroxil Capsule to Duricef Capsule (cefadroxil 500 mg). J. Appl. Pharmacol. 10: 303-308, 2002.
  30. Zhang Q and Li X.: Pharmacokinetics and residue elimination of oxytetracycline in grass carp, Ctenopharyngodon idellus. Aquacult. 272: 140-145, 2007. https://doi.org/10.1016/j.aquaculture.2007.08.033
  31. Zhang X, Wu LH, Shentu JZ, Chen ZG and Shi MF.: The Pharmacokinetics and Bioequivalence Study of Cefadroxil Capsules. Chinese J. of Clinic. Pharmacol. 17: 352-355, 2001.
  32. Zhang Y, Huo M, Zhou J and Xie S.: PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel. Comput. Methods Programs Biomed. 99: 306-314, 2010. https://doi.org/10.1016/j.cmpb.2010.01.007