• Archives of Pharmacal Research
• /
• v.2 no.1
• /
• pp.49-64
• /
• 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.

• The Korean Journal of Pharmacology
• /
• v.17 no.2
• /
• pp.63-67
• /
• 1981

Effect of acetazolamide on the diuretic action of furosemide was investigated in rabbits. The rates of urine flow and excretion of salts were significantly reduced when furosemide (0.5 mg/kg) was administered with acetazolamide (10 mg/kg) compared to the diuretic response of the single furosemide (0. 5 mg/kg) administration. Reduction in the fractional excretion rate of urine volume was more pronounced than the fractional excretion rate of salts. The results suggest that reduction of diuretic action on furosemide by combined administration of acetazolamide is probably due elevated urinary pH and interference in the mechanism of inhibition of chloride transport in the ascending Henle's limb.

• Journal of Pharmaceutical Investigation
• /
• v.13 no.4
• /
• pp.173-182
• /
• 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.)

• The Korean Journal of Pharmacology
• /
• v.22 no.2
• /
• pp.135-143
• /
• 1986

This study was designed to investigate the role of calcium in the function of an isolated perfused rabbit kidney and its effect on the diuretic action of furosemide. The administrations of hydralazine and verapamil produced remarkable diuretic actions mainly by decreasing renal resistance. The administration of furosemide in combination with hydralazine or verapamil produced remarkable diuretic action and there was no difference between the two groups. The administration of quinidine produced a diuretic action in spite of vasoconstriction and potentiated the diuretic action of furosemide. In the calcium-free perfusion medium, the administration of calcium produced a marked diuretic action in spite of vasoconstriction and potentiated significantly the diuretic action of furosemide. The administration of quinidine did not alter renal function and the diuretic action of furosemide, but the combined administration of quinidine and calcium showed antidiuretic effect due to excessive vasoconstriction in the calcium-free perfusion medium. Although the administration of verapamil produced a slight diuretic action in the calcium-free perfusion medium, verapamil did not alter the diuretic action of calcium as well as the diuretic actions of furosemide alone and in combination with calcium. The results of this experiment show that calcium, verapamil and quinidine produced diuretic actions and calcium potentiates the diuretic action of furosemide.

• Journal of Pharmaceutical Investigation
• /
• v.9 no.1
• /
• pp.7-14
• /
• 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
• /
• v.13 no.2
• /
• pp.73-87
• /
• 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.

• YAKHAK HOEJI
• /
• v.33 no.6
• /
• pp.345-349
• /
• 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
• /
• v.2 no.1
• /
• pp.35-47
• /
• 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
• /
• v.20 no.4
• /
• pp.193-198
• /
• 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.

• The Korean Journal of Pharmacology
• /
• v.25 no.1
• /
• pp.59-66
• /
• 1989

To determine the relation between cGMP and ion reabsorption in rat medullary thick ascending limb of Henle's loop (mTALH) the effects of loop diuretics, furosemide and ethacrynic acid, on the guanylate cyclase of rat mTALH were investigated. The interactions between loop diuretics and cyclooxygenase inhibitors, aspirin and indomethacin, on guanylate cyclase of rat mTALH were also investigated. Furosemide and ethacrynic acid increased guanylate cyclase activity and these effects were not inhibited by aspirin or indomethacin. Arachidonic acid potentiated the stimulatory effect of furosemide on guanylate cyclase. These results suggest that furosemide and ethacrynic acid activate guanylate cyclase directly, and in addition, furosemide affects indirectly via prostaglandin. The reabsorption of sodium chloride may be, at least partially, controlled by cGMP in mTALH.