• 핵의학기술
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• 제23권2호
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• pp.43-50
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• 2019

목적: 분당서울대병원 검체 검사실에서는 노후화된 전자동방사면역측정기의 교체로 인하여 새로운 자동화 장비가 도입이 되어, 검사원리가 IRMA법인 Insulin 검사로 장비 간 비교실험을 하게 되었다. 실험결과 장비간에 동일한 알고리즘인 선형 보간법을 적용하였음에도 불구하고 특히 저농도값에서 현저한 값 차이를 보였다. 이에 실험실내 보유중인 SR300, Gamma 10, Gamma Pro, Cobra 감마카운터 각각의 장비에 2가지의 알고리즘을 다르게 적용시켰을 때 값 차이를 알아보고자 하였다. 대상 및 방법: 검사원리가 IRMA법인 검사법 중 주로 자동화 장비에 검사가 시행 되고 있는 TSH, Ferritin, C-peptide, Insulin 4종목을 각각 10검체씩 저, 중, 고농도 값으로 선별하여 총 30개씩 동일한 검사항목에 대해서 SR300, Gamma 10, Gamma Pro, Cobra 카운터 장비에 선형 보간법과 스플라인 보간법으로 적용했을 때의 결과 값 차이를 비교하여 보았다. 결과: TSH, Ferritin, C-Peptide, Insulin 항목의 결과값에 선형 보간법과 스플라인 보간법을 다르게 적용시켜 장비간 상관성 검사를 시행한 결과 결정계수 $R^2$ 값은 0.9이상으로 모든 장비에서 상관성은 우수한 결과를 나타내었지만 통계적으로 유의성 검증결과 장비간 비교에서는 TSH를 제외하고 Ferritin, C-Peptide, Insulin 항목은 P값의 유의성이 0.001 미만으로 유의한 차이가 있었다. 선형 보간법과 스플라인 보간법 간의 결과값 비교에서는 TSH, ferritin, insulin을 제외하고 C-peptide 항목만 P값의 유의성이 0.03으로 보간법 간에 차이가 있음을 알 수 있었다. Insulin 낮은 값 영역에서 장비간 비교한 결과 P값의 유의성이 0.001 미만으로 Gamma Pro, Gamma 10, Cobra, SR300 카운터 장비간에 유의한 차이가 있었고 선형 보간법과 스플라인 보간법 간의 결과값 비교에서도 P값의 유의성이 0.001 미만으로 보간법간에 서로 유의한 차이가 있음을 알 수 있었다. 결론: 연구결과 검사원리가 IRMA법이면서 linear 보간법인 검사결과를 살펴보면 장비마다 Curve Fitting 방식 차이에 따라 Standard 0값을 설정해주는 기대치와 실측치의 값에 차이가 있음을 알 수 있었다. 이러한 원인으로 인해서 저농도 결과값에 영향을 미치고 장비 간에 차이가 유발됨을 알 수 있었다.

• Journal of Pharmaceutical Investigation
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• 제37권2호
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• pp.107-111
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• 2007

Epigallocatechin gallate (EGCC), a flavonoid, is the main component of green tea extracts. EGCG has been reported to be an inhibitor of P-glycoprotein (P-gp) and cytochrom P450 3A(CYP3A4). This study investigated the effect of long-term administration of EGCG on the pharmacokinetics of verapamil in rats. Pharmacokinetic parameters of verapamil were determined after oral administration of verapamil (9 mg/kg) in rats pretreated with EGCG (7.5 mg/hg) for 3 and 9 days. Compared to oral control group, the presence of EGCG significantly (p<0.01) increased the area under the plasma concentration-time curve (AUC) of verapamil by 102% (coad), 83.2% (3 days) and 52.3% (9 days), and the peak concentration $(C_{max})$ by 134% (coad), 120% (3 days) and 66.1% (9 days). The absolute bioavailability (A.B.%) of verapamil was significantly (p<0.01) higher by 8.4% (coad), 7.7% (3 days), 6.4% (9 days) compared to control (4.2%), and presence of EGCG was no significant change in the terminal half-life $(t_{1/2})$ and the time to reach the peak concentration $(T_{max})$ of verapamil. Our results indicate that EGCG significantly enhanced oral bioavailability of verapamil in rats, implying that presence of EGCG could be effective to inhibit the CYP3A4-mediated metabolism and P-gp efflux of verapamil in the intestine. Drug interactions should be considered in the clinical setting when verapamil is coadministrated with EGCG or EGCG-containing dietary.

• 약학회지
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• 제53권5호
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• pp.259-264
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• 2009

The present study was to investigate the effect of naringin, a flavonoid, on the pharmacokinetics of losartan in rats. Pharmacokinetic parameters of losartan in rats were determined after an oral administration of losartan (9 mg/kg) in the presence or absence of naringin (0.5, 2.5 and 10 mg/kg). The pharmacokinetic parameters of losartan were significantly altered by the presence of naringin compared with the control group (given losartan alone). Presence of naringin significantly (p<0.05, 2.5 mg/kg; p<0.01, 10 mg/kg) increased the area under the plasma concentration?time curve (AUC) of losartan by 43.7~63.0% and peak plasma concentration ($C_{max}$) of losartan by 31.7~45.5%. Consequently, the absolute bioavailability (AB) of losartan in the presence of naringin was 43.8~62.9%, which was enhanced significantly (p<0.05, p<0.01) compared to that in the oral control group (22.4%). The relative bioavailability (R.B.) of losartan increased by 1.44- to 1.63-fold in the presence of naringin. However, there was no significant change in the peak plasma concentration ($T_{max}$) and terminal half-life ($t_{1/2}$) of losartan in the presence of naringin. In conclusion, the presence of naringin significantly enhanced the oral bioavailability of losartan, implying that presence of naringin might be mainly effective to inhibit the cytochrome P450 (CYP)3A-mediated metabolism, resulting in reducing gastrointestinal and hepatic first-pass metabilism and Pglycoprotein (P-gp)-mediated efflux of losartan in small intestine. Concurrent use of naringin or naringin-containing dietary supplement with losartan should require close monitoring for potential drug interactions.

• 약학회지
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• 제49권3호
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• pp.230-236
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• 2005

The purpose of this study was to investigate the effect of naringin pretreatment on the bioavailability and phar-macokinetics of diltiazem and one of its metabolites, deacetyldiltiazem, in rabbits. Pharmacokinetic parameters of diltiazem and deacetyldiltiazem were determined after oral administration of diltiazem (15 mg/kg) pretreated with naringin (1.5, 7.5 and 15 mg/kg). Absorption rate constant ($k_a$) of diltiazem after oral administration of diltiazem pretreated with naringin was significantly (p<0.05 or p<0.0l) increased compared to the control group. Area under the plasma concentration-time curve (AUC) and peak concentration ($C_{max}$) of the diltiazem were significantly (p<0.05 or p<0.01) higher than those of the control. Absolute bioavailability ($AB\%$) of diltiazem pretreated with naringin ranged from $13.5\%$ to $18.6\%$, being enhanced compared to that of the control, $7.2\%$. Relative bioavailability ($RB\%$) of diltiazem was $1.9\~2.6$ times higher than that of the control group. There was no significant change in terminal half-life ($t_{1/2}$) and $T_{max}$ of diltiazem in the presence of naringin. AUC of deacetyldiltiazem pretreated with naringin was significantly (p<0.05) higher than (p<0.05) that of the control. But the metabolite ratios (MR) were significantly decreased (p<0.05), implying that pretreatment of naringin could be effective to inhibit the CYP 3A4-mediated metabolism of diltiazem. In this study, pretreatment of naringin significantly enhanced the oral bioavailability of diltiazem. These results suggested that the diltiazem dosage should be adjusted when it is administered with naringin or a naringin-containing dietary supplement in the clinical setting.

• The Korean Journal of Physiology
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• 제20권2호
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• pp.218-224
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• 1986

사람의 적혈구에서 여러 가지 음이온들의 등삼투성 암모늄 염으로 된 용액속에서의 용혈성을 이용하여 이들 음이온들이 $HCO_3\;^-$ 혹은 $OH^-$와 교환되어 이동되는 정도와 몇 가지 억제 물질의 영향, pH 및 온도 변화의 효과를 관찰하여 그 결과를 지금까지 방사성동위원소를 이용한 실험에서 보고된 성적들과 비교하였다. $SITS.\;H_2DIDS$, furosemide등은 농도에 비례하여 등삼투성 $NH_4Cl$ 용액에서의 용혈 시간을 연장시켰으며 $t_{1/2}$를 두배로 연장시킨 농도는 각각 $ 2.3{\times}10^{-7}M,\;3{\times}10^{-7}M,\;2.5{\times}10^{-5}M$이었다. Acetazolamide도 농도에 비례하여 적혈구 용혈 시간을 연장시켰으며 $t_{1/2}$을 2배로 연장시킨 농도는 $2.4{\times}10^{-5}M$이었다. 온도를 $2^{\circ}C$에서 $37^{\circ}C$까지 변화시키며 적혈구 용혈시간을 관찰했을 때 높은 온도 의존성을 보였으며 $1/t_{1/2}$을 Arrhenius plot하였을 때 $20^{\circ}C$에서 회절점을 보였고 activation energy는 $20^{\circ}C{\sim}37^{\circ}C$범위에서 11.2kcal/mol이었다. 여러 가지 무기 음이온의 투과도를 $t_{1/2}$을 기준으로 비교했을 때 $Cl^->NO_3\;^->SCN^->SO_4\;^{2-}>SSO_3\;^{2-}>HPO_4\;^{2-}$의 순이었으며 유기 음이온 중 oxalate는 $Cl^-$보다 높은 투과도를 succinate는 낮은 투과도를 보였다. 이상의 결과를 종합하면 등삼투성 암모늄염 용액에서의 적혈구 용혈성을 이용하여 음이온 이동에 대하여 관찰한 결과들이 지금까지의 동위원소를 이용한 실험 성적들과 유사한 결과를 보여주고 있으며 특히 이동률이 빠르거나, 높은 온도범위에서의 음이온의 이동을 관찰하는데는 동위원소를 이용한 실험의 단점을 보완할 수 있는 장점도 있어 이 방법의 적혈구 막을 통한 음이온의 이동 기전과 이에 영향을 미치는 인자들을 연구하는데 간편하고 유용하게 이용될 수 있을 것으로 사료된다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.117-117
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• 1997

Sandimmune Neoral$\^$(R)/ and Neoplanta$\^$(R)/ capsules were administered to twenty four healthy Korean male subjects at a cyclosporin A (CsA) dose of 175 mg in a 2 ${\times}$ 2 crossover investigation with a two-week wash-out phase. Concentrations of CsA in blood were measured by RIA method for over a period of 48 h. Result : The two formulations were found bioequivalent, but analysis of variance (ANOVA) indicated that there is a significant (p<0.01) period effect in AUC$\_$0-LAST/ (area under the blood concentration above assay limit of quantification-time curve) and C$\_$MAX/ (maximum blood concentration) between the administrations. Paired t-test revealed 6 and 9% decreases in AUC$\_$0-LAST/ and C$\_$MAX/, respectively at the second administration. This period effect on the pharmacokinetics of CsA may be relevant for the patients who need consecutive administration of the drug. A number of mechanisms, such as induction of the enzymes responsible for metabolism of the drug in the gut wall and/or liver and modulation of P-glycoprotein upon the consecutive dosing, appear consistent with the change, and needs experimental proof.

• 한국환경보건학회지
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• 제22권3호
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• pp.56-63
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• 1996

The results of the water purification studies using water parsley (Oenanthe javanica) were obtained as follows. The removal rate of nutrient salts increased with longer plant growth periods. The results of this study use the assumption, log(T+1) = $K(C_0-C)^A$, based on Prakish's Theory. The initial concentration was calculated from experimental data. A and K are closely related to the initial concentration. It is possible to model the concentration of residual salts, as time goes by, if concentration is constant. It was observed that water parsley neutralizes acid and alkali substances promptly. The maximum suitable neutralization period is 48 hours. But water parsley withered up in strong acid and alkali solutions within a week. The removal efficiency of Cd progresses in 2 steps, which are unrelated to the initial concentration of Cd. The first part of the curve shows the concentration rapid rate of Cd removal, followed by a levelling off. The removal rate of $NO_x-N$ in the sample water tank containing 0.5 ppm Cd was between 50~80% but the removal rate was less than 20% for the higher concentration. On the other hand, increased amounts of $PO_4-P$ in the sample water tank from the third day on suspected that $PO_4-P$ was desorbed from the water parsley. The accumulation efficiency of Cd in plant was increased in proportion to the initial concentration of Cd. The accumulation phenomenon was observed in the tanks more than 50~100 times.

• Asian-Australasian Journal of Animal Sciences
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• 제33권4호
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• pp.670-677
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• 2020

Objective: Interleukin-6 (IL-6) is a T cell-derived B cell stimulating factor which plays an important role in inflammatory diseases. In this study, the pharmacokinetic properties of LMT-28 including physicochemical property, in vitro liver microsomal stability and an in vivo pharmacokinetic study using BALB/c mice were characterized. Methods: LMT-28 has been synthesized and is being developed as a novel therapeutic IL-6 inhibitor. The physicochemical properties and in vitro pharmacokinetic profiles such as liver microsomal stability and Madin-Darby canine kidney (MDCK) cell permeability assay were examined. For in vivo pharmacokinetic studies, pharmacokinetic parameters using BALB/c mice were calculated. Results: The logarithm of the partition coefficient value (LogP; 3.65) and the apparent permeability coefficient values (P_app; 9.7×10^-6 cm/s) showed that LMT-28 possesses a moderate-high cell permeability property across MDCK cell monolayers. The plasma protein binding rate of LMT-28 was 92.4% and mostly bound to serum albumin. The metabolic half-life (t_1/2) values of LMT-28 were 15.3 min for rat and 21.9 min for human at the concentration 1 μM. The area under the plasma drug concentration-time curve and C_max after oral administration (5 mg/kg) of LMT-28 were 302±209 h·ng/mL and 137±100 ng/mL, respectively. Conclusion: These data suggest that LMT-28 may have good physicochemical and pharmacokinetic properties and may be a novel oral drug candidate as the first synthetic IL-6 inhibitor to ameliorate mammalian inflammation.

• 한국임상약학회지
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• 제18권2호
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• pp.120-123
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• 2008

The purpose of this study was to investigate the effect of naringin, one of flavonoids, on the pharmacokinetics and bioavailability of nimodipine in rabbits. Pharmacokinetic parameters of nimodipine were determined in rabbits after oral administration of nimodipine (16 mg/kg) with or without naringin (1, 5 or 15 mg/kg). Nimodipine was analyzed by high performance liquid chromatography using Hypersil ODS column. Naringin significantly (p<0.05) increased the area under the plasma concentration-time curve (AUC) and the peak concentration ($C_{max}$) of nimodipine at 5 and 15 mg/kg. The absolute bioavailability (AB%) of nimodipine by prescence of naringin (5 or 15 mg/kg) increased from 32.2-36.9% (p<0.05) compared to the control (22.0%). However, presence of naringin had no significant effect on the elimination rate constant ($K_{el}$) of nimodipine. There were no apparent changes of the time of peak concentration ($T_{max}$) of nimodipine by coadministration. These results suggest that the increased bioavailability and the significant changes of these pharmacokinetic parameters of nimodipine by naringin may be attributed to the potential of narigin to inhibit cytochrome P450 (CYP) 3A4 and P-glycoprotein efflux pump in the liver and intestinal mucosa.

• 한국임상약학회지
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• 제20권1호
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• pp.25-29
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• 2010

The purpose of this study was to investigate the effect of atorvastatin on the pharmacokinetics of nifedipine (6 mg/kg) after oral administration of nifedipine with or without atorvastatin (0.5 and 2.0 mg/kg) in rats, and also was to evaluate to the effect of atorvastatin on the CYP3A4 activity. The 50% inhibiting concentration ($IC_{50}$) values of atorvastatin on CYP3A4 activity is 46.1 ${\mu}M$. Atorvastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner. Coadministration of atorvastatin increased significantly (p<0.05, 2.0 mg/kg) the plasma concentration-time curve (AUC) and the peak concentration ($C_{max}$) of nifedipine compared to the control group. The relative bioavailability (RB%) of nifedipine was increased from 1.15- to 1.37-fold. Coadministration of atorvastatin did not significantly change the terminal half-life ($T_{1/2}$) and the time to reach the peak concentration ($T_{max}$) of nifedipine. Based on these results, we can make a conclusion that the significant changes of these pharmacokinetic parameters might be due to atorvastatin, which possesses the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein (P-gp) efflux pump in the intestinal mucosa. It might be suggested that atorvastatin altered disposition of nifedipine by inhibition of both the first-pass metabolism and P-glycoprotein efflux pump in the small intestine of rats. In conclusion, the presence of atorvastatin significantly enhanced the oral bioavailability of nifedipine, suggesting that concurrent use of atorvastatin with nifedipine should require close monitoring for potential drug interation.