Plasma Concentration, Distribution and Excretion of 14C-Milrinone in Rats following Single and Repeated Intravenous Administration.
Yasuhiko ImaiHiroshi OchiaiShinichiro KobayashiSaburo HiguchiYoshio ESUMIMatsuo TAKAICHIHideaki SEKIShinichi NinomiyaAtsushi TAKAOKazue Kimura
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雄性ラットに14C-ミルリノンを5mg/kg単回および反復静脈内投与したときの血漿中濃度，分布および排泄について検討した． 1．14C-ミルリノンをラットに単回静脈内投与したときの血漿中放射能濃度は2相性で低下し，最終消失相のt1/2は3.5hrであった．AUC0-∞，VdssおよびCLtotalはそれぞれ7.19μg equiv. ofmilrinone·hr/ml，873ml/kgおよび11.6ml/min/kgであった．血漿中の未変化体濃度は放射能濃度とほぼ同様の値で推移し，t1/2，AUC0-∞，VdssおよびCLtotalはそれぞれ3.2hr，7.35μg·hr/ml，727ml/kgおよび11.3ml/min/kgであった． 2．14C-ミルリノンを単回静脈内投与したときの放射能は各組織へ速やかに分布し，投与後15分に最高濃度を示した．投与後15分の組織内濃度は腎において血漿より約4倍高い値を示したが，他の組織ではいずれも血漿と同程度かそれ以下であった．その後，放射能は皮膚を除く各組織から速やかに消失した．14C-ミルリノンを7日間連続静脈内投与したときにはいずれの組織においても放射能の蓄積性は認められなかったが，皮膚からの消失が比較的遅かった．投与後24時間の全身オートラジオグラムにおいて放射能は被毛で認められたが，皮膚では検出されなかった．被毛では投与後72時間にも弱い放射能が検出された． 3．14C-ミルリノンを単回静脈内投与後168時間までの放射能の尿および糞中排泄率はそれぞれ79.2%および21.9%であり，投与量の101.1%が回収された．14C-ミルリノンを7日間連続静脈内投与したとき，放射能の尿および糞中への累積排泄率はそれぞれ74.9%および21.4%と単回投与時と同様であった．胆管カニューレを施したラットに14C-ミルリノンを単回静脈内投与後48時間までの尿，糞および胆汁中へ放射能がそれぞれ65.1%，10.4%および18.9%排泄され，本薬の主排泄経路は腎排泄であることが示された．Keywords:
Milrinone
Objective To observe the effect of milrinone on heart function and the plasma level of kaliuretic peptide(KP) in heart failure(CHF) patients.Methods Sixty-seven patients with CHF were enrolled in the study.The patients were randomly divided into milrinone group (32 cases) and control group(35 cases).The control group were treated with conventional drugs.Milrinone group were given intravenous milrinone for 7 days in addition to conventional treatment.The plasma level of KP was investigated before and after the treatment.Results The effective rate was higher in milrinone group than in control group.The cardiac function improved by 1 - 2 grades after milrinone treatment.The plasma level of KP in milrinone group was significantly declined after treatment than before and control group.Conclusion Milrinone is effective and safe for CHF and can decrease KP plasma level.
Milrinone
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Objective To observe the effect of treatment of congestive heart failure with milrinone. Methods 22 cases of congestive heart failure were treated with Chinese made milrinone intravenously. The heart function was evaluated by ultrasonocardiography after ten days of treatment and the results compared with the control group. Results The total effective rate of milrinone was 86.4%, while the control group was 27.8%. The difference between two groups was significant( χ 2=14.158, P 0.05). After the treatment, SV,CO,EF,FS improved significantly ( t=3.01-9.58, P 0.05). No serious side effects were detected during treatment. Conclusion Milrinone is an effective medicine for the treatment of congestive heart failure. [
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Objective To evaluate the content of aluminum in Milrinone Injection.Methods To determinate content of aluminum in Milrinone Injections by ICP-MS.Results There was a higher concentration of aluminum in Milrinone Injections.Conclusion It was necessary to control the content of aluminum in Milrinone Injection.
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Milrinone, 1,6-dihydro-2-methyl-6-oxo-[3,4?-bipyridine]-5-carbonitrile, is a positive inotropic cardiotonic agent with vasodilator properties that acts as selective phosphodiesterase 3 inhibitor in cardiac and vascular smooth muscle. Trade names of milrinone are Primacor, Corotrop, Corotrope, and Milrila. Milrinone, an amrinone derivative, is 20 to 50 times more active than amrinone and possesses reduced propensity to side effects. The use of milrinone has created controversy in the medical as the result of increased mortality rate among patients that received high amounts of milrinone in oral form. Reaserch show that it can be benifitial for patients with severe congestive heart failure when used as short-time intravenous therapy. Milrinone properties, stability, as well as mechanism of action and synthesis under laboratory and industry conditions have been described in this paper. For industrial purposes milrinone is synthesized by condensation of cyanoacetamide with 4-(dimethylamino)-3-(4-pyridinyl)-3-buten-2-one and 4-ethoxy-3-(4-pyridinyl)-3-buten-2-one in presence of a base, or by the reaction of 1-(4-pyridinyl)- 2-propanone with ethoxymethylenmalononitrile or 4-alkoxy-3-(4-pyridinyl)-3-buten-2-one with malononitrile without the use of external base. The starting compound for these syntheses is 4-picoline. Alternative synthesis of milrinone starts from 2-methyl-3-(4-pyridylidiene)-1,1,5-tricyano-1,4-pentadiene-5-carboxamide and 2-methyl-6-oxo-1,6-dihydro-3,4?-bipyridine-5-carboxamide. Lastly, methods for milrinone synthesis in laboratory, injection preparation and purification have been summarized.
Milrinone
Amrinone
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Objective: To observe the efficacy and safety of milrinone in the treatment of refractory heart failure. Methods: 45 patients with refractory heart failure received milrinone infusion 10 mg in 5% glucose 250ml continued for 6 h/d, for 7 days. Results: The total clinical response rate was 91.1%. Milrinone has significantly improved left ventricular systolic and diastolic function. Conclusion: Milrinone is an effective and safe drug, which can improve the left ventricular function in patients with refractory heart failure.
Milrinone
Refractory (planetary science)
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冠動脈バイパス術後の心不全症例に対する phosphodiesterase III阻害剤である milrinone の効果を検討した. 術後の心係数が2.0l/min/m2以下あるいは肺動脈楔入圧が12mmHg以上の心不全を有する20例を対象とし, milrinone (0.5μg/kg/min) を投与した Milrinone 群 (n=10), 非投与の Control 群 (n=10) の2群に分類し, 循環動態および臨床成績より比較検討した. 肺動脈楔入圧および全身血管抵抗は milrinone 投与により有意 (p<0.05) に低下した. 心係数は Control 群に比較し Milrinone 群で有意 (p<0.05) に高値で左室1回拍出仕事係数の上昇も同群で早期であった. Rate pressure product は有意な変化は認めなかった. Milrinone 群は Control 群に比較し中枢-末梢の温度較差も有意に (p<0.05) 低値であり, 術後のカテコールアミン必要量も同群で有意 (p<0.05) に低値であった. 本検討では milrinone 投与に伴う有意な副作用の増加は認められなかった. 以上の結果より冠動脈バイパス術後の心不全症例に対して milrinone は陽性変力作用および血管拡張作用を有していた. 従来の心不全の治療薬であるカテコールアミン製剤および血管拡張薬とともに本薬剤が有効な治療薬となることが示唆された.
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Objective To observe the efficacy and safety of milrinone for refractory heart failure. Methods Forty-eight patients with refratory heart failure received milrinone 10mg in 5% glucose 250 ml 6h/d , for 7 days. Results The total clinical effective rate was 91.7%, milrinone significantly improved left ventricular systolic and diastolic function. Conclusion Milinone is an effective and safe drug, and can improve the left ventricular function in patients with refractory heart failure.
Milrinone
Refractory (planetary science)
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Home-based milrinone therapy (HMT) is used as a bridge to cardiac transplant (CT). The safety, efficacy, and predictors of success of HMT were assessed. Forty-five patients with heart failure, referred for CT, were prospectively studied. After initial assessment, low-dose milrinone was titrated based on clinical response. Hemodynamic status was then reevaluated. Thirty-nine patients were discharged on HMT. Patients needing a left ventricular assist device (LVAD) despite milrinone (group I) and those not requiring LVAD (group II) were compared. Six of the 45 patients were ineligible for CT; 16 of 39 required LVAD as a bridge to CT despite milrinone (group I); 23 were stable on milrinone and did not require LVAD (group II). Group I was younger than group II (mean age 38.4 ± 14.5 years vs. 57.3 ± 5.9 years, p < 0.001). Initial acute response to intravenous milrinone [e.g., fall in the PCWP (–10.7 ± 9.5 vs. –2.7 ± 10.4, p = 0.02), rise in pulmonary artery oxygen saturations (16.5 ± 8.7 vs. 7.3 ± 10.9, p = 0.05)] was significantly better in group II than in group I. Acute hemodynamic response to milrinone predicts success of HMT as a bridge to CT.
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The interaction of the cAMP-phosphodiesterase inhibitor milrinone and the beta-adrenoceptor agonist isoproterenol was studied on guinea-pig isolated hearts. Milrinone, (10 microns) caused a positive inotropic response which differed from that of isoproterenol (7 nM) and decreased cardiac inotropic responses to the subsequent administration of isadrin despite a significant great rise in cAMP. The interaction of the drugs is assumed to be associated with the milrinone-induced increase in cGMP which is able to restrict myocardial cAMP-activated processes.
Milrinone
Phosphodiesterase inhibitor
Enoximone
Contractility
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Objective To compare the effects between milrinone and lrh-BNP for treating the peripartum cardiomyopathy heart failure.Methods After treated by routine measure,52 serious PPCM patients were randomized into two groups,Milrinone group(26 cases) treated with milrinone and Lrh-BNP group treated with Lrh-BNP.Results The total efficient rate in Lrh-BNP group(93.5%) was more higher than that of Milrinone group(79%).The index of heart function such as LVEF,FS,E/A,SV,CO,24 hours urine quantity and dyspnea improved after the therapy(P0.05),but the effects of Lrh-BNP group was more higher than that of Milrinone group(P0.05).Conclusion Lrh-BNP can be more efficient in treating PPCM than Milrinone.
Milrinone
Peripartum Cardiomyopathy
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