Oxolinic acid의 경구투여, 주사 및 약욕에 따른 넙치, Paralichthys olivaceus 체내 약물동태학적 특성
Pharmacokinetics of oxolinic acid in cultured olive flounder Paralichthys olivaceus by oral administration, injection and dipping
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Oxolonic acid (OA)를 넙치(평균체중 90 g)에 1회 경구투여(15, 30 및 60 ㎎/㎏ body weight), 1회 복강주사(10 및 20 ㎎/㎏ body weight) 및 1시간 동안 약욕(30 및 50 ppm)한 다음, 경시적(3시간~144시간)인 혈장내 OA의 잔류농도를 분석하 였다. 15, 30 및 60 ㎎/㎏ 농도로 경구투여한 모든 시험구에서 투여 10~15시간째 각각 1.92, 2.45 및 3.72 ㎍/㎖로 최대혈중농도를 나타내었다. 10 및 20 ㎎/㎏ 농도로 복강주사한 경우, 투여 10시간째 각각 4.1 및 4.8 ㎍/㎖로 최대혈중농도를 나타내었다. 약욕한 시험구의 경우, 30 및 50 ppm 시험구는 각각 투여 5~30시간째 0.22 및 0.38 ㎍/㎖로 최대혈중농도를 나타내었다. OA의 투여방법에 따른 넙치 체내 약물 혈중농도 측정결과를 바탕으로 one- compartment model로 WinNonlin program을 이용하여 OA의 흡수, 배설, 반감기 등 약물동태학적 매개변수(parameter)를 조사하였다. 15, 30 및 60 ㎎/㎏을 경구투여한 경우, 혈장농도-시간곡선하 면적(AUC)은 각각 70.93, 120.0 및 141.86 ㎍∙h/㎖, 혈중최고농도의 도달시간(Tmax)은 16.22, 20.39 및 17.33 h, 혈중최고농도 (Cmax)는 1.61, 2.40 및 3.01 ㎍/㎖로 계산되었다. 10 및 20 ㎎/㎏을 복강주사한 경우, 혈장농도-시간곡선하 면적(AUC)은 각 각 184.7 및 315.92 ㎍∙h/㎖, 혈중최고농도의 도달시간(Tmax)은 5.91 및 6.26 h, 혈중최고농도(Cmax)는 4.19 및 4.45 ㎍/㎖로 계산되었다. 30 및 50ppm으로 약욕한 경우, 혈장농도-시간곡선하 면적 (AUC)은 각각 17.58 및 21.69 ㎍∙h/㎖, 혈중 최고농도의 도달시간(Tmax)은 19.08 및 31.43 h, 혈중최고농도(Cmax)는 0.22 및 0.25 ㎍/㎖로 계산되었다.
Abstract
The pharmacokinetic properties of oxolinic acid (OA) were studied after oral administration, intraperitoneal injection and dipping to cultured olive flounder, Paralichthys olivaceus (average 90 g, 23±1℃). Plasma samples were taken at 3, 5, 10, 15, 24, 30, 48, 96 and 144 h post-dose. In oral dosage at 15, 30 and 60 ㎎/㎏, the peak plasma concentrations of OA, which attained at 10~15 h post-dose, were 1.92, 2.45 and 3.72 ㎍/㎖, respectively. In intraperitoneal injection with 10 and 20 ㎎/㎏, the peak plasma concentrations of OA, which attained at 10 h post-dose, were 4.1 and 4.8 ㎍/㎖, respectively. In dipping in 30 and 50 ppm for 1 h, peak concentrations were observed at 5 h and 30 h post-dose, were 0.22 and 0.38 ㎍/㎖, respectively. The kinetic profile of absorption, distribution and elimination of OA in plasma were analyzed fitting to a one-compartment model by WinNonlin program. Calculated parameters for a single oral dosage of 15, 30 and 60 ㎎/㎏, respectively, were: AUC (the area under the concentration-time curve)=70.93, 120.0 and 141.86 ㎍∙h/㎖; Tmax (time for maximum concentration)=16.22, 20.39 and 17.33 h; Cmax (maximum concentration)=1.61, 2.40 and 3.01 ㎍/㎖. Following intraperitoneal injection of 10 and 20 ㎎/㎏, these parameters were AUC=184.7 and 315.92 ㎍∙h/㎖; Tmax=5.91 and 6.26 h; Cmax=4.19 and 4.45 ㎍/㎖. Following dipping at 30 and 50 ppm, these parameters were AUC=17.58 and 21.69 ㎍∙h/㎖; Tmax=19.08 and 31.43 h; Cmax=0.22 and 0.25 ㎍/㎖.
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