• Biomolecules & Therapeutics
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• 제19권2호
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• pp.248-254
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• 2011

Biotransformation of pharmacologically inactive lactone prodrug simvastatin (SV) into pharmacologically active simvastatin ${\beta}$-hydroxy acid (SVA) exhibits inter-species differences due to variations in amount and activity of esterase enzymes. In this study, we investigated the pharmacokinetics (PK) of SV and its metabolite SVA following oral doses of SV from controlled-release (CR) tablets and immediate-release (IR) tablets in rodent and canine animal models that features different esterase activity. In rat PK study, no SV was detected in plasma for both formulations due to rapid hydrolysis of SV into SVA by plasma esterase. Besides, no significant differences in PK parameters of SV or SVA were observed between both species. In dog PK study, the relative oral bioavailability of CR tablets in terms of SV was 72.3% compared to IR tablets. Regarding formulation differences in dogs, CR tablets exhibited significantly lower $C_{max}$ (p<0.05), and higher $T_{max}$ (p<0.01) and MRT (p<0.01) for both SV and SVA compared to IR tablets. Accordingly, CR tablets of SV with prolonged drug release profiles in both species might be a potential candidate for a more effective delivery of SV with reduced side effects. Besides, similar PK parameters of SV and SVA in both species despite variation in enzyme activities suggested involvement of equally potent biotransformation pathways in these animal species.

• 대한수의학회지
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• 제43권2호
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• pp.203-210
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• 2003

The purpose of this study is to investigate the pharmacokinetics and tissue distribution of recombinant bovine somatotropin (rBST) after subcutaneous adminstration of $^{125}I-rBST$ in male and female rats. A solid state conjugation (Iodo-bead$^{(R)}$) method was confirmed useful for producing $^{125}I-rBST$ because the administration of the conjugated form enabled enough to determine time- concentration relationships of rBST in rats. Subcuatenous administrations showed sex differences that female ($t_{1/2,kc}$, 2.87 h) revealed rapid elimination as compared to male ($t_{1/2,ke}$, 4.81 h), with the absorption ($t_{1/2,ka}$ in male being 0.3 h and that in female 0.75 h) in the reverse order. For subcutaneous administration of rBST in male rats, the liver was the highest in amount, followed by kidney, testes, muscle, and stomach, at the slaughtering tame of 1, 6, 12 and 24 h. But the testes was the highest at the 48 h slaughtered animals, followed by liver, kidney, stomach, and muscle. In slaughtered females at 1, 6, and 12 h after the administration of rBST, the liver was the highest, followed by ovary, kidney, small intestine, and stomach. At 24 and 48 h slaughtered female rats, the ovary was the highest, the liver the second, and the kidney the third.

• 생명과학회지
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• 제26권1호
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• pp.123-128
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• 2016

본 연구의 최종 목표는 한방제제인 심적환과 심혈관계 양방 치료제인 cilostazol과 병용 투여 효과에 대한 포괄적이고 통합의학 측면에서 정확한 정보를 얻는 것이다. Cilostazol은 말초 동맥질환 치료제로 개발 된 항 혈소판 및 혈관확장제이다. 사이클릭 AMP protein kinase A를 활성 시켜 세포내 사이클릭 AMP (cAMP) 증가를 통하여 내피세포의 NO생산을 활성화 시킨다. 심적환을 단 회 또는 반복 투여 후 cilostazol의 약물 동태학적 효과를 평가하기 위하여 순수한 증류수 단회 용량과 증류수에 심적환 콜로이드 현탁액을 각각 대조군과 시험군에 투여 하여 30분 후, 두 그룹에 cilostazol를 투여하였다. 혈청은 cilostazol 약물 투여 30분 전에 수집 하였으며, cilostazol 약물 처리 후 0.25, 0.5, 0.45 및 1, 2, 4, 6, 8, 24시간 후에 각각 수집 하였다. 그 다음 실험군과 및 테스트 그룹 사이에 실로 스타 졸에서 관찰 된 약동학 적 변화를 평가 하였다. 통계적으로 유의 한 차이는 심적관 단독 투여와 반복투여군 그룹의 약물 동태 학에서 관찰되지 않았다. 이러한 연구 결과는 만성 질환 환자에서 한약제인 심적환의 투여는 cilostazol의 약동학에 영향을 미치지 않았음을 보여 주었다. 본 연구에서 얻어진 결과는 만성 혈관질환 환자에서 심적환과 cilostazol의 병용 투여를 제안하며 두 약물간의 잠재적 인 약물 상호 작용에 대한 cilostazol의 생체 이용률에 영향을 미치지 않을 것이라 판단된다.

• 한국임상약학회지
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• 제9권2호
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• pp.88-91
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• 1999

The purpose of this study was to compare the pkarmacokinetic parameters of vancomycin using a 2-compartment model in 8 Korean healthy volunteers and 8 lymphoma patients. Vancomycin (1.0 g) was administered by IV infusion over 60 minutes. The $\beta-phase$ rate constant $(\beta)$, apparent volume of distribution at steady srate $(V_{ss})$, total body clearance (CL) and area under the plasma level-time curve (AUC) of vancomycin in healthy volunteers were $0.15\pm0.02\;hr^{-1},\;33.8\pm4.12\;L/kg,\;5.36\pm0.61\;L/hr\;and\;185.8\pm20.5\;{\mu}g/ml{\cdot}hr$, respectively. The corresponding values in lymphoma patients ere $0.09\pm0.02\;hr^{-1},\;38.2\pm5.11\;L/kg,\;4.58\pm0.52\;L/hr\;and\;218.3\pm22.9\;{\mu}g/ml{\cdot}hr$. There were significant differences (p<0.05) in ${\beta}$ and CL between healthy volunteers and lymphoma patients.

• Archives of Pharmacal Research
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• 제19권4호
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• pp.297-301
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• 1996

Plasma profile of niflumic acid following oral administration of talniflumate tablets (Somalgen) was compared to that of niflumic acid tablets in man. Plasma niflumic acid was assayed by HPLC method. Plasma niflumic acid profile from the tainiflumate tablets was similar to that from the niflumic acid tablets resulting in no differences in $AUC, C_max, t_max$ and MRT. It demonstrates that talniflumate is a prodrug of niflumic acid, and undergoes extensive first-pass biotransformation to niflumic acid. However, plasma niflumic acid concentration at 30 min after tainiflumate dosing was significantly (p<0.05) higher than that of niflumic acid dosing. The more potent analgesic activity of talniflumate than niflumic acid might be related to this higher plasma drug concentration at the earlier phase. Considering that tainiflumate is less irritant to gastrointestinal mucosa than niflumic acid, talniflumate seems to be advantageous over niflumic acid in terms of activity and side effects.

• 한국임상약학회지
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• 제5권2호
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• pp.1-12
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• 1995

The purpose of this investigation was to determine pharmacokinetic parameters of gentamicin using linear least square regression(LLSR) and Bayesian analysis in Korean normal volunteers and appendicitis patients. Nonparametric expected maximum(NPEM) algorithm for population pharmacokinetic parameters was used. Gentamicin was administered every 8 hours for 3 days by infusion over 30 minutes. The volume of distribution(V) and elimination rate constant(K) of gentamicin were $0.215\pm0.0562,\;0.226\pm0.0325L/kg\;and\;0.339\pm0.0443,\;0.357\pm0.0243hr^{-1}$ for normal volunteers and appendicitis patients using LLSR analysis. Population pharmacokinetic parameters, VS and KS were $0.228\pm0.0614L/kg\;and\;0.00356\pm0.00041(hr{\cdot}mL/min/1.73m^2)^{-1}$ for appendicitis patients using NPEM algorithm. The V and K were $0.232\pm0.0568L/kg\;and\;0.337\pm0.0385hr^{-1}$ for appendicitis patients using Bayesian analysis. There were no differences in gentamicin pharmacokinetics between LLSR and Bayesian analysis.

• 약학회지
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• 제45권2호
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• pp.153-160
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• 2001

This research developed an intravenous (IV) vancomycin dosing nomogram based on the clinical pharmacokinetic data of Korean adult patients. Total 99 pairs of steady-state peak and trough serum concentrations of vancomycin were obtained from 73 adult patients in a tertiary general hospital. Serum vancomycin concentrations were determined to assess the appropriateness of initial vancomycin dosing. Only 47.2% of the cases were within therapeutic range. To characterize the clinical pharmacokinetics (PK) of vancomycin, PK parameters including elimination rate constant ( $K_{e}$) half-life( $T_{1}$2/), clearance (C $l_{van}$), volume of distribution ( $V_{d}$) were calculated by using one-compartment, first order pharmacokinetic equations. PK parameters were evaluated based on the differences of patients'renal function and age. Regression analysis showed a significant correlation between C $l_{van}$ and $C_{cr}$ (C $l_{van}$ = -1.89+0.914 $C_{cr}$ , r=0.763) and between $K_{e}$ and $C_{cr}$ , ( $K_{e}$=-0.0037+0.00139 $C_{cr}$ =0.724). The relationship between $K_{e}$ and $C_{cr}$ , and the mean $V_{d}$ were utilized for developing the nomogram to individualize the initial dosing regimen of vancomycin for the patients with various degrees of renal functions. The nomogram may be used as an efficient tool to determine safe and effective doses of vancomycin for the Korean adult patients.nts.nts.nts.s.nts.

• 한국임상약학회지
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• 제8권2호
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• pp.107-112
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• 1998

Lovastatin is a lipid lowering agent for the treatment of hypercholesterolemia and belongs to a new class of pharmacologic compounds called the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. By competitively inhibiting HMG CoA reductase, lovastatin disrupts the biosynthesis of cholesterol in hepatic and peripheral cells and increases the synthesis of high-density-lipoprotein HDL) receptors. Following oral administration, the lactone ring of lovastatin is hydrolysed to the active inhibitor of HMG CoA reductase, lovastatin acid. Lovastatin is known to have poor oral absorption and wide individual variation. In this study, bioequivalence test of two lovastatin formulations, the test drug ($Lovaload^{TM}$, Chong Kun Dang Pharmaceutical Co.) and the reference drug ($Mevacor^{TM}$, Chung Wae Pharmaceutical Co.) were conducted according to the guidelines of Korea Food and Drug Administration (KFDA). A total of 18 healthy male volunteers, $31.90\pm3.60$ years old and $72.17\;7.88$ kg of body weight in average, were evaluated in a randomized crossover manner with a 2-week washout period. Concentrations of lovastatin acid in plasma were measured upto 12 hours following a single oral administration of eight tablets (20 mg of lovastatin per tablet) by high-performance liquid chromatography with UV detection at 238 nm. The area under the concentration-vs-time curve from 0 to 12 hours $(AUC_{0-12h})$ was calculated by the trapezoidal summation method. The statistical analysis showed that there are no significant differences in $AUC_{0-12h),\;C_{max}\;and\;T_{max}$ between the two formulations ($6.72\%,\;1.52\%,\;and\;0.88\$, respectively). The least significant differences between the formulations at $\alpha$=0.05 were less than $20\%\;(11.65\%,\;19.73\%,\;and\;14.81\%\;for\;AUC_{0-12h},\;C_{max}\;and\;T_{max}$, respectively). The $90\%$ confidence intervals for these parameters were also within $\pm20\%\;(-1.50{\leq}{\delta}{\leq}15.00$, $-12.50{\leq}{\delta}{\leq}15.50,\;and\;-9.64{\leq}{\delta]{\leq}11.40{\leq}\;for\;\;AUC_{0-12h}$ ,$C_{max}\;and\;T_{max}$, respectively). In conclusion, the new generic product $Lovaload^{TM}$ was proven to be bioequivalent with the reference drug.

• 산업식품공학
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• 제21권3호
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• pp.273-279
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• 2017

커큐민 분말은 항산화 및 항염증 등의 생리활성을 내세우며, 건강기능식품 및 일반식품의 마케팅 포인트로 광범위하게 사용되고 있다. 커큐민의 낮은 체내 흡수율은 생리적 기능성에도 영향을 미칠것으로 사료되어 리포좀 형태나 인지질 결합 형태로 커큐민의 제형 개발이 활발이 진행되고 있다. 본 연구에서는 커큐민의 체내 흡수율을 높이고, 실제 산업에의 활용도를 높이기 위해 커큐민을 서브마이크론 입자 형태의 제형으로 개발하여, 일반 커큐민 형태와의 흡수율을 비교해보고자 하였다. 본 연구 결과, 일반 커큐민 보다 서브마이크론 입자 형태 커큐민의 체내 흡수율이 남녀 평균 28배 더 높게 나타났다. 서브마이크론 입자 형태 커큐민의 체내 흡수율은 성별에 따라 다르게 나타났으며, 남성의 경우는 22배, 여성의 경우는 35배 흡수율이 높게 나타났다. 편의성을 증진시킨 농축제제와 기존 제제의 흡수율은 $C_{max}$ 값이 각각 166.0과 177.7로 통계적 유의성이 나타나지 않았다. 단회 투여 후 8시간 동안의 AUC 값 역시 약 952와 약 849로 나타나 제제의 동등성에서 유의적인 차이는 없었다. 결론적으로, 본 연구를 통해 일반 커큐민 보다 서브마이크론 입자 형태 커큐민의 체내 흡수율이 남녀 평균 약 28배 증진되는 것으로 확인되었으며, 편의성을 증진시킨 농축제제와 일반 제제의 흡수율이 거의 동일하게 나타났다.

• Journal of Ginseng Research
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• 제23권3호
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• pp.172-175
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• 1999

홍삼액기스의 투여가 에탄올의 곡선하면적(AUC)과 제거속도상수(elimination rate constant)에 미치는 효과에 대하여 웅성 백서 14마리와 건강한 남성 자원자 10명을 대상으로 연구하였다. 백서에게 홍삼액기스 200 mg/kg를 투여하거나 같은 분량의 물을 투여한 후 즉시 $50\%$ 에탄올, 3.2g/kg의 용량을 구강 투여하였다. 에탄올의 곡선하면적(AUC)과 제거속도상수는 홍삼액기스를 투여할 경우 $29.2{\pm}6.2\;g{\cdot}min.{\cdot}dl^-$와, $0.51{\pm}0.06\;mg{\cdot}dl^-{\cdot}min.^-$를 나타내었으며, 홍삼액기스를 투여하지 않을 경우는 각각 $28.0{\pm}5.6\;g{\cdot}min.{\cdot}dl^-$와 $0.5{\pm}0.1\;mg{\cdot}dl^-{\cdot}min.^-$를 나타내었다. 이들 차이는 통계적으로 유의하지 않았다. 또한 인체에서는 일인당 홍삼액기스 3그램을 100 ml의 물에 희석하거나 또는 동일분량의 물을 투여하고 곧 이어서 소주 2.4 m/kg의 용량을 마시게 하였다. 자원자의 에탄올에 대한 곡선하면적과 제거속도상수는 홍삼액기스의 투여군이 $10.6{\pm}2.0\;g{\cdot}min.{\cdot}dl^{-}$와 $0.21{\pm}0.05\;mg{\cdot}dl^-{\cdot}min.^-$를,대조군에서는 $11.0{\pm}2.2\;g{\cdot}min.{\cdot}dl^{-}$와 $0.22{\pm}0.04\;mg{\cdot}dl^-{\cdot}min.^-$를 나타내었으며 역시 두 군간의 차이는 없었다. (평균${\pm}$표준편차) 이런 결과들로 미루어 홍삼액기스의 투여로 에탄올의 약동학에 의미있는 변화를 초래하기란 어려울 것으로 생각된다.