• 생명과학회지
• /
• 제28권4호
• /
• pp.472-477
• /
• 2018

Pravastatin은 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) 환원효소 억제제이며, 혈청 콜레스테롤 농도를 낮추어 심혈 관계 위험성 및 사망률을 감소시킨다. 이번 연구는 부형제, 안정화제, 붕해제, 활택제, 착색제로 사용되는 첨가제들 및 pravastatin과의 적합성 연구를 위해 진행되었다. 모든 첨가제들과의 혼합은 PTP 포장으로 포장되어 가속시험장치($40^{\circ}C/75%$ Relative Humidity)에서 3개월 동안 진행하였다. 가시적인 시험결과로는 백색의 가루 또는 밝은 갈색으로 변화는 없었다. 모든 첨가제들과 pravastatin 혼합 시 pravastatin 함량 및 순도에 있어 아주 적은 수준으로 영향을 주었으며, 그 중 pravastatin의 lactone 함량의 변화가 조금 있는 첨가제로는 microcrystalline cellulose 및 croscamellose sodium이었다. 초기의 pravastatin의 lactone 함량과 비교 시 약 0.22% 및 0.18%로 증가하였고 모든 첨가제들과의 전체 혼합 시도 3개월에서 lactone 함량이 0.43%로 증가하는 것을 확인 하였다. 이번 연구 결과들은 복용편리성을 위한 pravastatin 정제 크기 감소 연구에 크게 기여 할 것으로 판단된다.

• 산업식품공학
• /
• 제13권4호
• /
• pp.243-250
• /
• 2009

프라바스타틴 나트륨은 HMG-CoA(3-hydroxy-3-methylglutaryl coenzyme A) 환원효소 저해제로서, 콜레스테롤 생합성의 초기 율속단계(rate-limiting step)에 작용하여 메 발로네이트(mevalonate)의 합성을 저해하는 광범위한 고지혈증 치료제이다. 본 연구에서는 효율적 발효와 고품질의 정제를 통한 생산성 향상을 위해 수행하였다. 프라바스타틴 나트륨의 경쟁력있는 생산성 향상을 위하여 Streptomyces carbophilus KCCM 10370을 UV 돌연변이 처리하여 프라바스타틴 나트륨의 생산량을 약 45배 향상시키는 S. carbophilus K-212(KCCM 10370) 선별하였다. 생산성을 극대화시키기 위하여 콤팩틴 나트륨의 연속식 투입이 회분식 투입보다 생산량이 24%, 전환율 4.3%로 향상 되었으며, 본배양에서 콤팩틴 나트륨의 농도를 연속적으로 투입하여 0.1%(w/v) 이하로 유지시켜 프라바스타틴 나트륨의 생산량이 0.49%, 전환율 70%로 확인하였다. 발효가 종료된 후 배양액을 Diaion HP20 수지 컬럼, 분배(Partition), 그리고 ODS(Octa-Decylsilyl Silicagel) 수지 컬럼 크로마토 그래피를 하여 유럽약전기준(EP)에 적합한 순도 99.7% 이상, 70~72%의 수율이었다. 프라바스타틴 나트륨을 적외부스펙트럼측정법, 자외부스펙트럼측정법, 수소핵자기공명스펙트럼측정법 및 탄소핵자기공명스펙트럼측정법으로 분석한 결과 유럽약전기준(EP)과 일치하였다.

• 한국임상약학회지
• /
• 제24권4호
• /
• pp.231-239
• /
• 2014

Background and objective: Pravastatin has been shown to have favorable risk-benefit profile when it is administered to hypercholesterolemic subjects to prevent cardiovascular events. However, subjects with impaired OATP1B1 activity may be more susceptible to pravastatin-induced muscle toxicity than subjects with normal OATP1B1 activity. A systematic review was conducted to evaluate the effect of SLCO1B1 genetic polymorphism on pharmacokinetics of pravastatin. Method: Medline$^{(R)}$ and Embase$^{(R)}$ were searched for relevant studies until July 2013. The search terms used were pravastatin AND (SLCO1B1 OR OATP1B1 OR LST1 OR SLC21A6) AND (gene OR $genetic^*$ OR $genomic^*$ OR $pharmacogenet^*$ OR $pharmacogenom^*$ OR $polymorph^*$). Results: A meta-analysis of the area under the concentration-time curve (AUC) of pravastatin in $SLCO1B1^*15$ and $SLCO1B1^*1a/^*1a$ was conducted. Five studies met all the inclusion criteria and methodological requirements. There was no statistically significant difference in the AUC value between $SLCO1B1^*15$ and $SLCO1B1^*1a/^*1a$ (p=0.728). However, $SLCO1B1^*15$ participants exhibited significantly higher AUC values than $SLCO1B1^*1b/^*1b$ carriers (p<0.001). In case of $SLCO1B1^*15^*15$ carriers, they had significantly higher AUC value than $SLCO1B1^*1a/^*1a$ subjects (p=0.002). Lastly, compared with to the subjects of $SLCO1B1^*1a/^*1a$, the carriers of heterozygous $SLCO1B1^*15$ increased the AUC value of pravastatin statistically significantly in Asian population (p=0.014). Conclusion: The present meta-analysis suggests that subjects with $SLCO1B1^*15$ are associated with increased AUC of pravastatin.

• 대한한방내과학회지
• /
• 제38권3호
• /
• pp.327-335
• /
• 2017

Objective: The goal of this preclinical study was to compare the dyslipidemic effect of pravastatin with that of herbal medicine in rats. Methods: In total, 40 rats were divided into 4 groups: Normal (10 rats), Control (10 rats), Statin alone (10 rats), and the MO-PM-S group (10 rats), which was given the powder of the cortex of Magnolia officinalis Rehd. et Wils., the root of Polygonum multiflorum Thunb, and pravastatin. The Control group, the Statin alone group, and the MO-PM-S group were all given a high-fat (45%) diet that made them obese. After 2 weeks of drug administration, the dyslipidemic effect of pravastatin was compared with that of herbal medicine in rats by analyzing the lipid profiles, measuring the body weights, and taking biopsies (liver, aorta). Results: The herbal medicine and the statin complex group got a much lower TG level and a slightly higher HDL-cholesterol level than the other groups. However, it got a higher total cholesterol and LDL-cholesterol level than the other groups. In biopsies, 30% of the Statin alone group and 10% of the MO-PM-S group showed mild histopathologic findings in the liver. Conclusion: The cortex of the Magnolia officinalis Rehd. et Wils. and the root of Polygonum multiflorum Thunb have dyslipidemic effects from the perspective of a TG level and HDL-cholesterol. However, the herbal mixture has a raising effect on both the LDL-cholesterol and the total cholesterol levels. Therefore, we cannot conclude that the herbal mixture helps to prevent dyslipidemia. In liver biopsies, the group administered with both the herbal mixture and the statin showed less histopathologic findings than the group administered with statin alone. This means that the herbal mixture helps to prevent fatty degeneration of the liver.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
• /
• pp.332-332
• /
• 1994

식이습관을 바꾸지 않는 상태에서 4주간의 placebo 투여후 혈청 Total-C치가 240mg/dl 이상인 원발성 고콜레스테 혈증환자 25예씩 두군으로 하여 제1군은 lovastatin 20mg에서 80mg을 1일 1회 저녁에 12주간 투여하였고, 제2군은 pravastatin 5mg을 12주간 아침 저녁으로 2회 경구 투여하였다. Lovastatin과 pravastatin 12주 투여후 혈청 Total-C치는 309$\pm$46mg/d1에서 201$\pm$37mg/d1로, 281$\pm$41mg/d1에서 218$\pm$31mg/d1로, 혈청LDL-C치는 230$\pm$46mg/d1에서 125$\pm$40mg/d1로, 199$\pm$46mg/d1에서 137$\pm$37mg/d1로 각각 유의하게 감소 하였다. (p < 0.005)혈청 Apo B치는 183$\pm$32mg/d1에서 114$\pm$26mg/d1로, 164$\pm$38mg/d1에서 123$\pm$20mg/d1로, 혈청 Apo B / Apo A-1 ratio는 1.6$\pm$0.4에서 1.0$\pm$0.3으로, 1.4$\pm$0.5에서 1.0$\pm$0.3으로 각각 유의하게 감소하였다. (p < 0.005) Lovastatin 및 pravastatin 투여후 임상적으로 의미있는 중상이나 검사상 이상 소견은 관찰되지 않았다.

• The Korean journal of internal medicine
• /
• 제33권6호
• /
• pp.1210-1223
• /
• 2018

Background/Aims: The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma. Methods: High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed. Results: HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice. Conclusions: These results suggest that the IL-17-leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.

• 분석과학
• /
• 제22권5호
• /
• pp.407-414
• /
• 2009

가스크로마토그래피-질량분석기 (GC/MS)를 이용하여 뇨 중의 cholesterol, lanosterol, desmosterol 의 동시분석법을 개발하였다. 뇨 시료는 ${\beta}$-glucuronidase/arylsulfatase를 첨가하여 효소가수분해한 후 에틸아세테이트-헥산 (2:3, v/v)으로 추출하였으며 추출한 잔사를 MSTFA/TMSI/TMCS (100:2:5 v/v/v)로 유도체화한 후 GC/MS의 selective ion monitoring mode에서 분석하였다. 개발된 분석방법은 검량선에서 좋은 직선성 ($r^2=0.998{\sim}0.999$)과 회수율 (80.0%~113%)을 보였으며 5-200 ng/mL의 농도범위에서 15% 이내의 정확도와 정밀도를 보였다. 개발된 분석법은 고지혈증 유도 쥐에 pravastatin을 7일동안 70과 250 mg/kg/day로 경구투여한 후 채취한 뇨 시료를 분석하는데 적용하였다. 측정 결과 뇨 중 스테롤의 농도가 약물 투여한 쥐에서 대조군에서 보다 유의성 있게 낮아 약물효과를 관찰할 수 있었다. 이 결과로부터 개발된 방법을 뇨 중 스테롤의 농도를 정량함으로서 스타틴약물의 효과를 측정하는데 적용할 수 있음을 확인하였다.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
• /
• pp.44-58
• /
• 2003

• 대한임상약리학회:학술대회논문집
• /
• 대한임상약리학회 2006년도 제15차 추계학술대회
• /
• pp.41-42
• /
• 2006

• Journal of Microbiology and Biotechnology
• /
• 제27권5호
• /
• pp.956-964
• /
• 2017

Compactin and pravastatin are competitive cholesterol biosynthesis inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase and belong to the statin drugs; however, the latter shows superior pharmacokinetic characteristics. Previously, we reported that the bacterial P450, CYP105D7, from Streptomyces avermitilis can catalyze the hydroxylation of 1-deoxypentalenic acid, diclofenac, and naringenin. Here, we demonstrate that CYP105D7 could also catalyze compactin hydroxylation in vitro. In the presence of both bacterial and cyanobacterial redox partner systems with an NADPH regeneration system, the reaction produced two hydroxylated products, including pravastatin (hydroxylated at the C6 position). The steady-state kinetic parameters were measured using the redox partners of putidaredoxin and its reductase. The $k_m$ and $k_{cat}$ values for compactin were $39.1{\pm}8.8{\mu}M$ and $1.12{\pm}0.09min^{-1}$, respectively. The $k_{cat}/K_m$ value for compactin ($0.029min^{-1}{\cdot}{\mu}M^{-1}$) was lower than that for diclofenac ($0.114min^{-1}{\cdot}{\mu}M^{-1}$). Spectroscopic analysis showed that CYP105D7 binds to compactin with a $K_d$ value of $17.5{\pm}3.6{\mu}M$. Molecular docking analysis was performed to build a possible binding model of compactin. Comparisons of different substrates with CYP105D7 were conclusively illustrated for the first time.