• Archives of Pharmacal Research
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• 제2권1호
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• pp.49-64
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• 1979

In an atempt to elucidate further physicochemical properties of furosemide-PVP coprecipitates, extensive investigations such as TLC, UV,IR, NMR, X-ray diffraction, TGA and DTA studies were carried out for the furosemide test systems. X-ray diffraction studies revealed that the pure furosemide and the furosemide contained within a physical mixture were crystalline in nature. However, there was no crystallinity evident in the 1:5 furosemide-PVP 40,000 coprecipitate system, even after standing for two years. The various ratio furosemide-PVP 40,000 coprecipitate systems revealed that the coprecipitate containing a greater amount of PVP 40,000 than that of furosemide showed a crystalline state of furosemide and that the minimum amounts of PVP to make amorphous form of furosemide was 1:1 ratio of furosemide to PVP. From the furosemide-PVP coprecipitate systems with PVP of different molecular weights of 10,000, 40,000 and 360,000, all the 1:1 ratio coprecipitates did not exhibit any crystallinity of furosemide, whereas all the 2:1 ratio coprecipitates showed a presence of crystalline furosemide. All the coprecipitated preparations with PEG 4,000 and with PEG 6,000 showed the diffraction peaks indicating the presence of crystalline furosemide. The comparison of infrared spectra of the physical mixture and the coprecipitate showed an interaction such as association between the functional groups of furosemide and PVP in the molecular level, whereas the studies by TLC, UV and NMR showed its dissociation in methanol solution. The weight losses in TGA curves showed all the same patterns. However, a little different transition form in DTA thermograms was shown between the physical mixture and the coprecipitate, indicating the different thermal property.

• 대한약리학회지
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• 제17권2호
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• pp.63-67
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• 1981

Furosemide의 이뇨작용에 대한 acetazolamide의 영향을 알아보고자 토끼를 4군으로 나누어 saline(0.5ml/kg), acetazolamide (10mg/kg), furosemide (0.5mg/kg), acetazolamide (10mg/kg)+furosemide(0.5mg/kg)를 각각 정맥주사하였다. 1) Acetazolamide와 furosemide 병합투여시 furosemide를 단독투여했을 때의 뇨량, 뇨중 전해질 배설량에 비하여 유의한 감소를 보였다. 2) Acetazolamide와 furosemide 병합투여시와 furosemide를 단독투여시의 뇨중 전해질과 뇨량의 fraxtional excretion rate를 비교하면, 병합투여시에 감소되어 나타났으며 뇨중전해질보다 뇨량에서 그 정도가 심하였다. 3) Acetazolamide와 furosemide 병합투여시 뇨 pH가 furosemide 단독투여시보다 높게 나타났다. 4) 뇨중 $Cl^-$배설량에 대한 $Na^+\;+K^+$배설량의 비는 acetazolamide + furosemide 병합투여군과 furosemide 단독투여군에서 유의한 차이를 보이지 않았다. Acetazolamide와의 병합투여로 나타나는 furosemide 이뇨작용의 감소는 뇨 pH의 증가 또는 ascending Henle‘s limb에서의 $Cl^-$재흡수 억제의 감소에 기인하는 것으로 사료된다.

• Journal of Pharmaceutical Investigation
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• 제13권4호
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• pp.173-182
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• 1983

The influence of prazosin (0.1 mg/kg i.v.) on the excretion and diuretic action of furosemide (2mg/kg i.v.) in rabbits was studied to investigate an interaction between ${\alpha}-adrenergic$ blocking agent, prazosin and furosemide. The results were as follows; 1) With the combined administration of prazosin and furosemide, the plasma concentration of furosemide was increased, the urinary excretion rate and renal clearance of furosemide were reduced, and tile biological half-life of furosemide was increased. 2) The diuretic action of furosemide was significantly reduced with the combined administration of prazosin: maximal decrease in urine volume, urinary electrolytes, clearance of $Na^+$ and $Cl^-$, and GFR and RPF, as well as maximal increase in $Na^+$ reabsorption rate were noted 10 minutes after administration of furosemide (2mg/kg i.v.)

• 대한약리학회지
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• 제22권2호
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• pp.135-143
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• 1986

저자는 적출관류 토끼 신장기능에서 칼슘의 역할과 furosemide의 이뇨작용에 미치는 영향을 관찰하여 다음과 같은 결과를 얻었다. hydralazine놔 verapamil을 주로 신혈관 저항의 감소로 이뇨작용을 나타냈다. furosemide를 hydralazine 또는 verapamil 병합투여시 뚜렷한 이뇨작용이 나타났으며 두군 사이에 차이는 없었다. quinidine은 신혈관 수축을 일으켰으나 이뇨작용이 나타났으며 furosemide의 이뇨작용을 항진시켰다. 칼슘제외된 관류액으로 관류시 칼슘은 신혈관 수축에도 불구하고 이뇨작용이 나타났으며 furosemide의 이뇨작용을 항진시켰다. quinidine은 칼슘이 제외된 상태에서 신장기능 및 furosemide의 이뇨작용에 영향을 미 치지 못하였으나 calcium 병합투여시 과도한 신혈관 수축으로 항 이뇨작용을 보였다. verapamil은 칼슘이 제외된 상태에서 약간의 이뇨작용을 보였지만 칼슘 및 furosemide의 이뇨작용을 변화시키지 못하였다. 이상의 성적은 적출관류 토끼 신장에서 칼슘, verapamil 및quinidine이 이뇨작용이 있으며 칼슘은 furosemide의 이뇨작용을 항진시킨다.

• Journal of Pharmaceutical Investigation
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• 제9권1호
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• pp.7-14
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• 1979

The relative efficacy on the renal function of rabbits by oral administration of furosemide and 1 : 2 furosemide-PVP coprecipitate was compared by measuring the urine volume in response to maximal response and the amounts of electrolytes excreted in urine. The furosemide produced a rapid onset, short duration of diuresis, in contrast, the 1: 2 furosemide-PVP coprecipitate, a rapid onset, significantly larger magnitude, and longer duration of diuresis and therefore the bioavailability of furosemide from the coprecipitate were increased significantly. The average urine volume and the amount of sodium and potassium excreted in urine were increased about 2.9-, 14.8-, and 1.8-fold from furosemide, and about 6.2-, 24.2-, and 3.6-fold from 1 : 2 furosemide- PVP 40,000 coprecipitate, rerpectively, comparing by their control values.

• Journal of Pharmaceutical Investigation
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• 제13권2호
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• pp.73-87
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• 1983

The matrix affects the dissolution of furosemide, which is almost insoluble in the dissolution medium. In order to understand the effect of the matrix on the dissolution of furosemide, lactose, starch, $Avicel\;^{\circledR}pH\;101$, $Avicel\;^{\circledR}pH\;301$, $SiO_2$ and talc were used as the matrix and the solvent deposition method were used. The dissolution characteristics of four dissolution medium were compared to each other using various ratio of drug-to-matrix. The results are as follows: 1) Lactose was shown to be superior and talc was to be inferior to the other matrixes investigated. 2) A maximum dissolution rate and dissolution amount of furosemide were observed in 1 : 10 ratio of the drug-to-matrix. 3) $T_{80%}$ of 1 : 10 ratio of the drug-to-matrix in pH 7.2 was 1 min. from FM-lactose and 30 min. from FM-talc. $T_{50%}$ in pH 4.2 is 2 min. from furosemide-lactose and 150 min. from furosemide-talc. Total amount of furosemide in pH 1.2 at 30 min. were enhanced 13.3 fold in furosemide-lactose and 3.5 fold in furosemide-talc compared to the control. Diuretic action of those furosemide-lactose and furosemide-talc was also evaluated by monitoring changes in urinary excretion of sodium, potassium and urine volume in rat. The accumulated urine volume were enhanced 1.7 fold in furosemide-lactose (1.5) compared to the furosemide.

• 약학회지
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• 제33권6호
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• pp.345-349
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• 1989

This paper was attempted to investigate effect of angiotensin inhibitor (loading dose 25, 50, $100{\mu}g/kg$ and maintenance dose 12.5, 25, $50{\mu}g/kg/hr$) on the pharmacokinetics of furosemide (5 mg/kg i.v) in rabbit. The plasma concentrations of furosemide increased by angiotensin inhibitor and the relative bioavailability of furosemide increased from 118.1% to 193.2% by the inhibitor. The protein binding of furosemide decreased by angiotensin inhibitor in bovine serum albumin ($2.17\;{\times}\;10^{-4}M$) by equilibrium dialysis method. Consequently, dosage regimen of furosemide might be adjusted carefully when furosemide is administered with angiotensin inhibitor.

• Archives of Pharmacal Research
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• 제2권1호
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• pp.35-47
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• 1979

In order to increase the dissolution rate of furosemide(4-choro-N-furfury1-5-sulfamoy1 anthranilic acid_, various ratio coprecipitates with water-soluble polymers, such as polyvinylpyrrolidone and polythylene glycol, of different molecular weight, were prepared and quantitatively studied by comparing their dissolution characteristics of furosemide at powder state and at nondisintegrating disk state containing constant surface area at various temperatures and rotating velocities. The dissolution characteristics of furosemide from pure furosemide disks and 1:2(w/w) furosemide-PVP coprecipitate disks were in accordance with Noyes-Nernst equation and the rate constant of dissolution was proportional to the square root of rotating velocity of the disks. The intrinsic rate of dissoluton at 150 rpm, 37.deg.C was $2.21{\times}10^{-7}$ for the PVP 10, 000 COPRECIPITATE, $1.64{\times}10^{-7}$ for the PVP 40, 000 coprecipitate, and$ 1.44 {\times} 10^{-7}$for the PVP 360, 000 corprecipitate, while the rate was $1.27{\times}10^{-8}M/cm^{2} min$ for pure furosemide, repectively. The activation energy of dissolution was about 17, 000 for furosemide and about 7, 300 cal/mole for the 1:2 furosemide PVP 40, 000 coprecipitate, respectively.

• Journal of Pharmaceutical Investigation
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• 제20권4호
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• pp.193-198
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• 1990

To increase the dissolution rate of furosemide, cogrinding or coprecipitating of furosemide with povidone was carried out. The ground mixture of furosemide with povidone was prepared by cogrinding in a ceramic ball mill and the coprecipitate was prepared by solvent method using methanol. The povidone ground mixture and the coprecipitate showed a faster and more enhanced dissolution rate than the physical mixture or intact furosemide. The IR, DTA and TGA studies showed the physicochemical modifications of furosemide from the ground mixture and the coprecipitate. An interaction, in the ground mixture and in the coprecipitate, such as association between the functional groups of furosemide and povidone might occur in the molecular level. The coprecipitating and cogrinding techniques with povidone provided a promising way to increase the dissolution rate of poorly soluble drugs.

• 대한약리학회지
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• 제25권1호
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• pp.59-66
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• 1989

흰쥐의 헨레고리 수질 비후상행각에서의 전해질 재흡수와 cyclic GMP와의 관계를 알아보고자 수질비후상행각의 guanylate cyclase에 대한 furosemide와 ethacrynic acid의 영향을 관찰하였다. 또한 이들 작용과 prostaglandin의 상관관계를 알아보고자 guanylate cyclase에 대한 고효능이뇨제(furosemide, ethacrynic acid)와 cyclooxygenase 억제제들과의 상호작용을 함께 관찰하였다. furosemide와 ethacrynic acid는 guanylate cyclase의 활성을 현저히 증가시켰으며 이 증가작용은 aspirin이나 indomethacin에 의해 차단되지 않았다. arachidonic acid는 furosemide의 guanylate cyclase 활성증가작용을 유의하게 증강시켰다. 이들의 결과는 furosemide와 ethacynic acid가 직접적인 guanylate cyclase 활성촉진작용을 가지고 있으며 또한 furosemide는 prostaglandin을 경유한 간접적인 guanylate cyclase 활성 촉진작용을 가지고 있음을 나타낸다. 또한 수질 비후상행각에서의 전해질 재흡수에 cyclic GMP가 관여할 가능성을 시사한다.