Amoxicillin trihydrate의 단독 경구투여 및 정맥투여에 따른 뱀장어, Anguilla japonica 체내 약물동태학적 특성
Pharmacokinetics of amoxicillin trihydrate in cultured eel Anguilla japonica by single oral and intravenous administrations
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아목시실린(Amoxicillin trihydrate; Amox)을 뱀장어(평균 체중 220±10 g)에 1일 1회 경구투여(40 및80 mg/kg body weight) 및 정맥투여(1 mg/kg)한 다음,경시적(0시간∼720시간)으로 혈장내 Amox의 잔류농도를 분석하였다. 40 및 80 mg/kg 농도로 경구투여한 모든 시험구에서 투여 6시간째 각각 3.3±0.5 및3.4±0.1 ㎍/㎖로 최대혈중농도를 나타내었다. Amox 의 모든 시험구는 투여 720시간째 혈중에서 검출되지 않았다. Amox의 경구투여방법에 따른 뱀장어 체내 약물 혈중농도 측정결과를 바탕으로 WinNonlin program을 이용한 2-compartment model로 하여 Amox 의 흡수, 배설, 반감기 등 약물동태학적 매개변수(parameter)를 조사하였다. 2-compartment model을 이용한 분석을 통하여 40 및 80 mg/kg Amox를 경구투여한 경우, 혈장농도-시간곡선하 면적(AUC)은 각각 464 및 667 ㎍ㆍh/㎖, 혈중최고농도의 도달시간(Tmax)은 2.1 및 3.6 hr, 혈중최고농도(Cmax)는 3.04및 3.4 ㎕/㎖로 계산되었다. 1 mg/kg Amox을 정맥투여한 경우, 혈장농도-시간곡선하 면적(AUC)은748 ㎍ㆍh/㎖, 혈중최고농도(Cmax)는 4.2 ㎕/㎖로 계산되었다. 1일 1회 단독으로 40 및 80 mg/kg Amox를각각 경구 투여시의 뱀장어내 생체내이용율(F%;bioavailability)은 각각 1.6, 1.1%로 매우 낮게 나타났다. 이러한 결과는 아목시실린을 삼수화물 형태로사용함에도 낮은 어류내 생체내이용율을 가진다는사실을 알 수 있다.
Abstract
The pharmacokinetic properties of amoxicillin trihydrate (Amox) were studied after single oral administration and single intravenous injection to cultured eel, Anguilla japonica, respectively (average 220±10 g, 28±1℃). Plasma samples were taken at 3, 5, 10, 15, 24, 30, 48, 96 and 144 h post-dose. The kinetic profile of absorption, distribution and elimination of Amox in plasma were analyzed fitting to a two-compartment model by WinNonlin program. In oral dosage of 40 and 80 ㎎/㎏ body weight, the peak plasma concentrations of Amox, which attained at 3～12 h post-dose, were 3.4 and 3.3 ㎍/㎖, respectively. In intravenous injection with 1 ㎎/㎏, the peak plasma concentrations of Amox, which attained at 9 h post-dose, was 7.2 ㎍/㎖. The following parmeters were calculated for a single oral dosage of 40 and 80 ㎎/㎏ body weight, respectively: AUC (the area under the concentration-time curve)〓 464 and 667 ㎍․h/㎖; Tmax (time for maximum concentration)〓 2.1 and 3.6 h; Cmax (maximum concentration)〓 3.04 and 3.4 ㎍/㎖. Following intravenous injection at 1 ㎎/㎏, this parameters were AUC= 748 ㎍․h/㎖; Cmax〓 4.2 ㎍/㎖. The apparent oral bioavailability at 40 and 80 ㎎/㎏ were 1.6 and 1.1%, respectively. Despite using the trihydrate form of amoxicillin, the oral bioavailability was low in eel.
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