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Fırat Üniversitesi Sağlık Bilimleri Veteriner Dergisi
2014, Cilt 28, Sayı 2, Sayfa(lar) 085-088
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Topikal Selamektin Uygulaması Sonrası Koyun ve Keçilerde Plazma Konsantrasyonlarının Araştırılması
Burcu GÜL BAYKALIR, Gürdal DAĞOĞLU
Fırat Üniversitesi, Veteriner Fakültesi, Farmakoloji ve Toksikoloji Anabilim Dalı, Elazığ, TÜRKİYE
Anahtar Kelimeler: Selamektin, koyun, keçi, HPLC
Özet
Selamektinin koyun ve keçilerde etiket dışı kullanılmasını takiben plazma konsantrasyonu ve farmakokinetik parametrelerinin belirlenmesi amacıyla yapılan bu çalışmada 1 yaşında dişi 12 adet koyun ile 12 adet keçi kullanılmıştır. Her iki gruba tek doz 12 mg/kg selamektin (Stronghold® %12 240 mg) topikal olarak uygulanmıştır. 35 günlük süre boyunca farklı aralıklarla kan örnekleri alınmış ve gerekli analizler yapılmıştır. Selamektinin plazma konsantrasyonu yüksek basınçlı sıvı kromotografisiyle ölçülmüştür (HPLC). Analizler sonucunda ortalama plazma konsantrasyonu, plazma maksimum konsantrasyon (Cmax), eğri altında kalan alan (AUC), ortalama kalış süresi (MRT) ve plazma maksimum konsantrasyona ulaşma süresi (Tmax) koyunlarda sırasıyla 1427.27±90.52 pg/mL, 4.78±0.61 ng/mL, 810.35±115.95 ng.saat/mL, 10.86±0.89 gün ve 72 saat; keçilerde ise 1195.03±70.81 pg/mL; 3.27±0.52 ng/mL, 664.42±72.62 ng.saat/mL, 10.46±0.74 gün ve 72 saat olarak belirlenmiştir. Sonuç olarak, selamektinin koyun ve keçilere topikal olarak uygulanması halinde plazma konsantrasyon düzeyi, Cmax ve AUC değerlerinin koyunlarda keçilere göre daha yüksek bulunduğu (P<0.05), MRT ve Tmax değerleri arasında ise önemli bir fark olmadığı (P>0.05) tespit edilmiştir.
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    Because macrocyclic lactones (ML) has a wide spectrum and are reliable drugs, they are used widely at animals to treat parasitic diseases1-3. Selamectin is created using by chemical modification of doramectin, a new semi-synthetic product4. It has mininum dosage of 6 mg/ kg with very wide spectrum including most of ecto and endoparasites and marketed worldwide with the name of Stronghold® (Europe) and Revolution® (USA) as a topical product5-7.

    Avermectin's pharmacokinetic profiles significantly affected by important factors, such as species, age, sex and physiological condition of the animal, aplication route and formulation of drug, nutrition, intra-species and interspecies variatons, differences at metabolism or elimination process8-10. Avermectins has less soluble ratings in water and highly soluble in oil11. Due to high soluble rating in oil, adipose tissue has been served as drug storage. High proportion fat soluble of this group of drugs; has a large volume of distribution and accumulated at liver and adipose tissue to be eliminated slowly2.

    There is no data on the kinetic disposition of selamectin following topical administration in sheep and goats. Thus, the aim of study was to determine plasma concentrations and some pharmacokinetic profiles during 35 days after administration topically selamectin used widely at animals to treat ecto and endoparasitic diseases and a new product avermectin derivation with doses of 12 mg/kg at sheep and goats.

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    Experimental animals and sampling: Twelve healty and 1 year old, weighing 40 kg on average sheep and 30 kg goats were used in this study. The animals were allocated into two groups of twelve animals each. They were all female provided by Agriculture and Livestock Research Centre of Fırat University. The animals were housed and fed (barley and concentrated feed) for at least 30 days. Water was supplied ad libitum. Both group was applied topically skin on the back at a dose of 12 mg/kg bodyweight selamectin (Stronghold®, Pfizer, ABD). Heparinized blood samples (5 mL) were collected by jugular vein puncture prior to drug administration then at 0, 1, 2, 3, 4, 6, 7, 8, 9, 10, 14, 16, 18, 21, 28 and 35 days. Blood samples were centrifuged at 3500 g for 15 min.

    Analytical procedures: The plasma concentration of selamectin was analysed by high performance liquid chromatography (HPLC) according to the method of Sutra et al.12 and Walker and Fenner13 using HPLC system (Schimadzu LC-20 AT, Japan). The mobile phase13 consisted of acetonitrile- watertetrahidrofuran (68:17:15, v/v/v) and at a flow rate of 1 mL/minute. A C18 analytical column (5 μ; 250x4.6 mm, Phenomenex, UK) was used for analysis. Fluorescence detection was at an excitation wavelength of 360 nm and emission wavelength of 450 nm. Each sample run was 15 min.

    Pharmacokinetic and statistical analysis of data: The plasma concentration-time data after administration of drug for each animal were created by using WinNonlin® 4.1 software programme (Scientific Consulting Inc., USA). Pharmacokinetic parameters for each animal were analyzed using topical route of administration and non-compartmental model. SPSS software (for Windows 11.5) was used for the statistical analysis. Mann Whitney U-test was used to test for between species differences in plasma concentration and some pharmacokinetic parametres. Results mean ± standart deviation (SD) were expressed and mean values were considered statistically was different at P<0.05.

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    The mean pharmacokinetic parameters of selamectin after topical administration in sheep and goats are shown in Table 1 with mean plasma concentrations time curve goats and sheep (Figure 1 and 2). Plasma concentration of sheeps (1427.27±90.52 pg/mL) was found to significantly higher compared to goats (1195.03±70.81 pg/mL) (P<0.05). Accordingly, Cmax and AUC in sheep were found to be higher compared goats (P<0.05). However, there was no statistically significant differences in terms of the values of MRT and Tmax (P>0.05).


    Büyütmek İçin Tıklayın
    Table 1: Mean (±SD) pharmacokinetic parameters of selamectin in sheep and goats following topical administration at a dose rate of 12 mg/kg (n: 20)


    Büyütmek İçin Tıklayın
    Figure 1: Mean (±S.D.) plasma concentration time profile after topical administration selamectin at a dose of 12 mg/kg in sheep


    Büyütmek İçin Tıklayın
    Figure 2: Mean (±S.D.) plasma concentration time profile after topical administration selamectin at a dose of 12 mg/kg in goats

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    Pharmacokinetic studies on selamectin1,14,15 usually carried out in cats and dogs. In sheep, goats and cattle, there was no study conducted. In this study, there were evaluated mean plasma concentration levels, Cmax, AUC, MRT and Tmax values during following 35 days after topically administration of selamectin with a single dose 12 mg/kg in sheep and goats. Animal species, sex, route of administration, and feeding, body-fat ratio, physico-chemical structure and formulation of drug were known on pharmacokinetic of selamectin1,8,14-22.

    As a result of the analysis, for sheep mean plasma concentration, Cmax, AUC, MRT and Tmax values determined as 1427.27±90.52 pg/mL, 4.78±0.61ng/mL, 810.35±115.95 ng.h/mL, 10.86±0.89 days and 72 hours, respectively and for goats plasma concentration, Cmax, AUC, MRT and Tmax values determined as 1195.03±70.81 pg/mL, 3.27±0.52 ng/mL, 664.42±72.62 ng.h/ml, 10.46±0.74 days and 72 hours, respectively.

    In a study conducted by Sarasola et al.15, after topically administration of selamectin Cmax and Tmax values were determined as 86.5±34.0 ng/mL and 3 days in dogs, respectively and for cats 5513±2173 ng/mL and 15 hours, respectively.

    In a study conducted by Dupuy et al.1, after topically administration of selamectin with 6 mg/kg dose Cmax, AUC, MRT, Tmax values determined as 12.72±5.13 ng/mL, 192.08±63.85 ng.d/mL, 12.55 days, 4.86±3.56 days at male dogs, respectively and 22.65±11.95 ng/mL, 370.97±146.87 ng.d/mL, 12.55 days, 5.2±1.87 days for female dogs, respectively.

    As a result, selamectin was topically administired for treatment and control of parasitic diseases of sheep and goats, mean plasma concentration, Cmax and AUC values were found higher in sheeps compared to goats and no significant difference were identified between goats and sheep for MRT and Tmax values.

    This study has contributed to pharmacokinetic values of selamectin at sheep and goats. We believe that new studies must be conducted for dose and dose limits, planned a variety of pharmacokinetic studies, revealing drug interactions and determination of residual period of selamectin at sheep, goat and cattle.

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    1) Dupuy J, Derlon AL, Sutra JF, et al. Pharmacokinetics of selamectin in dogs after topical application. Vet Res Commun 2004; 28: 407-413.

    2) Gokbulut C, Bilgili A, Hanedan B, et al. Sex-related plasma disposition of ivermectin following pour-on administration in goats. Vet Parasitol 2009; 162: 342-345.

    3) Novotony MJ, Krautmann MJ, Ehrhart JC, et al. Safety of selamectin in dogs. Vet Parasitol 2000; 91: 377-391.

    4) Bishop BF, Bruce CI, Evans NA, et al. Selamectin: A novel broad-spectrum endectocide for dogs and cats. Vet Parasitol 2000; 91: 163-176.

    5) Benchaoui HA, Clemence RG, Clements PJM, et al. Efficacy and safety of selamectin against fleas on dogs and cats presented as veterinary patients in Europe. Vet Parasitol 2000; 91: 223-232.

    6) Maggie AF, David J. A review of the off-label use of selamectin (stronghold®/ revolution®) in dogs and cats. Acta Vet Scand 2008; 50: 46.

    7) McTier TL, Jones RL, Holbert MS, et al. Efficacy of selamectin against adult flea infestations (ctenocephalides felis felis and ctenocephalides canis) on dogs and cats. Vet Parasitol 2000; 91: 187-199.

    8) Lo PKA, Fink DW, Williams JB, Blodinger J. Pharmacokinetic studies of ivermectin effects of formulation. Vet Res Commun 1985; 9: 251-268.

    9) McKellar QA, Benchaoui HA. Avermectins and milbemycins. J Vet Pharmacol Ther 1996; 19: 331-351.

    10) Mugford CA, Kedderis GL. Sex-dependent metabolism of xenobiotics. Drug Metab Rev 1998; 30: 441-498.

    11) Bassissi MF, Alvinerie M, Lespine A. Macrocyclic lactones: distribution in plasma lipoproteins of several animal species including humans. Comp Biochem Phys C 2004; 138: 437-444.

    12) Sutra JF, Cadiergues MC, Dupuy J, Franc M, Alvinerie M. Determination of selamectin in dog plasma by high performance liquid chromatography with automated solid phase extraction and fluorescence detection. Vet Res 2001; 32: 455-461.

    13) Walker DK, Fenner KS. A sensitive method for the measurement of the novel pet endectocide, selamectin (UK-124,114), in dog and cat plasma by chemical derivatisation and high-performance liquid chromatography with fluorescence detection. J Pharmaceut Biomed 2000; 24: 105-111.

    14) Pillai U, Harran L, Blackwell D, Updike L. Toxicokinetics of selamectin in rats and dogs. In: Soback S, McKellar Q. (Editors). Proceeding of the 8th International Congress of the European Association for Veterinary Pharmacology and Toxicology (EAVPT). J Vet Pharmacol Ther 2000; 23(1).

    15) Sarasola P, Jernigan AD, Walker DK, et al. Pharmacokinetics of selamectin following intravenous, oral and topical administration in cats and dogs. J Vet Pharmacol Ther 2002; 25: 265-272.

    16) Alvinerie M, Lacoste E, Sutra JF, Chartier C. Some pharmacokinetic parameters of eprinomectin in goats following pour-on administration. Vet Res Commun 1999; 23: 449-455.

    17) Alvinerie M, Sutra JF, Cabezas I, Rubilar L, Perez R. Enhanced plasma availability of moxidectin in fasted horses. J Equine Vet Sci 2000; 20: 575-578.

    18) Atta AH, Abo-Shıhada MN. Comparative pharmacokinetics of doramectin and ivermectin in sheep. J Vet Pharmacol Ther 2000; 23: 49-52.

    19) Craven J, Bjorn H, Hennessy DR, Friis C, Nansen P. Pharmacokinetics of moxidectin and ivermectin following intravenous in pigs with different body compositions. J Vet Pharmacol Ther 2001; 24: 99-104.

    20) Escudero E, Carceles CM, Diaz MS, et al. Pharmacokinetics of moxidectin and doramectin in goats. Res Vet Sci 1999; 67: 175-179.

    21) Nowakowski MA, Lynch MJ, Smith DG, et al. Pharmacokinetic and bio-equivalence of parenterally administered doramectin cattle. J Vet Pharmacol Ther 1995; 18: 290-298.

    22) Wilkinson PK, Pope DG, Baylis FP. Pharmacokinetics of ivermectin administered intravenously to cattle. J Pharm Sci 1985; 75: 1105-1107.

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