• Archives of Pharmacal Research
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• 제28권4호
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• pp.463-468
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• 2005

The purpose of the present study was to develop a standard protocol for imidapril hydrochloride bioequivalence testing. For this reason, a specific LC-MS method was developed and validated for the determination of imidapril in human plasma. A solid-phase extraction cartridge, $Sep-pak^{R}$ C18, was used to extract imidapril and ramipril (an internal standard) from deproteinized plasma. The compounds were separated using a XTerra $MS^{R}$?C18 column ($3.5 {\mu}m, 2.1\times150 mm$) and $acetonitrile-0.1\%$ formic acid (67:33, v/v) adjusted to pH 2.4 by 2 mmol/L ammonium formic acid, as mobile phase at 0.3 mL/min. Imidapril was detected as m/z 406 at a retention time of ca. 2.3 min, and ramipril as m/z 417 at ca. 3.6 min. The described method showed acceptable specificity, linearity from 0.5 to 100 ng/mL, precision (expressed as a relative standard deviation of less than $15\%$), accuracy, and stability. The plasma concentration-versus-time curves of eight healthy male volunteers administered a single dose of imidapril (10 mg), gave an $AUC_{12hr}$ of imidapril of $121.48\pm35.81 ng mL^{-1} h$, and $C_{max} and T_{max}$ values of $32.59\pm9.76 ng/mL and 1.75\pm0.27 h$. The developed method should be useful for the determination of imidapril in plasma with sufficient sensitivity and specificity in bioequivalence study.

• Journal of Yeungnam Medical Science
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• 제16권1호
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• pp.69-75
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• 1999

1993년 일본의 Tanabe 제약에서 개발된 염산 Imidapril (Tanatril$^{(R)}$)은 새로운 작용지속형 ACE inhibitor이며 강압효과와 안정성이 뛰어나고, 마른기침 등의 부작용이 다른 ACE inhibitor 보다는 적은 것으로 보고되고 있다. 1997년 10월 6일부터 1998년 12월까지 영남대학교 의과대학 부속병원 순환기 내과에 내원하여 고혈압이 처음 진단되었거나 진단받은 후에도 강압제 치료를 받지 않았던 환자 중 경증(1기)에서 중증(3기) 본태성 고혈압(JNC V 분류의거)을 보인 30명중 최종분석이 가능한 21명(부작용으로 투약을 중단한 1명 포함)을 대상으로 하였다. 임상시험 종료 시 측정한 확장기 혈압은 $88.7{\pm}9mmHg$로 평균 하강량은 13.8mmHg이었다. 혈압 강하효과 판정에서 16명이 혈압 하강군으로 분류되어 혈압강하효과는 76.2%(16/21)였다. Imidapril 단독 투여로 치료 종료시 정상 혈압(l40/90mmHg 미만)을 보인 경우는 10명(47.6%)이었다. 임상시험중 나타나는 부작용으로는 마른기침, 두통, 현기증, 오심, 상복부 불쾌감, 졸리움 등이 있었으며 총 7명에서(33.3%) 부작용이 관찰되었고, 심한 위장관계 불편감을 호소한 한 예를 제외하고는 모두 일상 생활에 불편을 주지는 않는 상태였으며, 시간이 경과할수록 그 정도가 점차로 약해졌다. ACE inhibitor의 가장 흔한 부작용 중의 하나인 마른기침은 모두 2명(9.5%)에서 관찰되었다. 새로운 ACE inhibitor인 Imidapril은 다른 ACE inhibitor와 비슷한 강압효과와 안정성을 보이며, 특별히 심각한 부작용을 보이지 않고, 그 중에서도 특히 마른기침 발현 빈도는 9.5%로 다른 제제에 비해 현저히 낮았으며, 그 정도가 미미하여 감량없이 계속투여가 가능했다.

• 한국임상약학회지
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• 제22권4호
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• pp.330-339
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• 2012

Background : Hypertension is treated with both lifestyle modification and pharmacotherapy. The Seventh Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7), published in 2003, provides a streamlined management approach to hypertension for the primary care physician. The JNC-7 is the gold standard also in Korea. According to the JNC-7, special therapeutic considerations are recommended for high-risk individuals with compelling indications. The presence of compelling indications in any given patient should be considered when selecting specific pharmacotherapy to treat hypertension. However, in patients with compelling indications, it is unknown that hepatotoxicity is caused by Calcium Channel Blocker (CCB), one of 1st anti-hypertensive drugs. Now, the CCB is the most used 1st anti-hypertensive drug in Korea Therefore, we evaluated the changes in blood liver function parameters (ALT, AST, Total bilirubin, serum albumin) for the study group. Methods : We randomly collected and retrospectively analyzed Electronic Medical Record data (n=28,788) of patients, and who took calcium channel blockers(non-dihydropyridines; diltiazem, verapamil, dihydropyridines; amlodipine, barnidipine, benidipine, clinidipine, efonidipine, felodipine, isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nimodipine), with having liver function tests (LFTs) from July 1st 2009 to June 30th 2010 at the Seoul National University Hospital in Korea. Control groups are two antihypertensive agents: RAS blockade (ARB; candesartan, irbesartan, losartan, olmesartan, telmisartan, valsartan, ACE-I; cilazapril, enalapril, fosinopril, imidapril, perindopril, ramipril) and, Diuretics (loop; furosemide, torsemide, thiazide; hydrochlorothiazide[HCTZ], indapamide). Patients not having LFT results at these three standard points of time(baseline, during, medication, and after finishing medication) were excluded. The collected data were analyzed by using the SPSS (Version12.0) and Microsoft Excel (Version2007). Results : 711 patients who were treated CCB (297), RAS blockade (232) or Diuretics (182) monotherapy were selected for the study. In selected patients, liver damage degree(changes of each LFTs value) was higher in diuretics group than other groups, followed by RAS blockade and CCB. In diuretics group's was loop-diuretics group was higher than thiazide-diuretics group. In CCB group, Nondihydropyridine-CCB's damage degree was higher than Dihydropyrine-CCB's that. Conclusions : Despite the limitations due to the retrospective study, among patients with abnormal LFTs, the use of CCBs led to a less liver damage than other 1st anti-hypertensive agents. It can be recommended CCBs as one of the initial treatments of hypertension in patients with liver disease.