• Archives of Pharmacal Research
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• v.12 no.3
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• pp.154-159
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• 1989

Pharmacokinetics and urinary excretion of sulfamethoxazole were investigated in healthy sheep. From the plasma disappearance curves after intravenous bolus injection (50 mg/kg), the half-life and volume of distribution were found to be 76 $\PM$14 min and 0.41 $\PM$ 0.18 lit/kg respectively. Body clearance was 4.06 $\PM$ 1.03 ml/kg/min. Very low Concentration of ddrug was present in plasma after 3 hours of administration and plasma level at 6 hour was only 4.4 $\PM$ 2.0 $\mu$g/ml. The renal clearance of sulfamethoxazole (22 $\PM$ 2.17 ml/min/10 kg) exeeded the creatinine clearance (9.78 $\PM$ 1, 57 ml/min/ 10 kg) which may be due to involvement of active tubular secretion and pH dependent back diffusion. Half of the dose of sulfamethoxazole was excreted as unchanged free drug while acetylated amine comprised of 20 percent within the first 6 hours of drug administration.

• YAKHAK HOEJI
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• v.29 no.6
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• pp.362-366
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• 1985

These paper was attempted to investigate the mechanism of increased blood level of sulfisomidine by cimetidine pretreatment pharmacokinetically. Especially, effect of cimetidine pretreatment on both renal clearance and biliary clearance of sulfisomidine was studied in rabbits. The results are as follows. The blood level of sulfisomidine administered intravenously in dose of 25mg/kg was elevated significantly by cimetidine pretreatment. Relative bioavailability and biological half-life were increased significantly by cimetidine pretreatment. Overall elimination rate constant ($betha$) and distribution rate constant ($K_{13}$) of sulfisomidine were decreased significantly by cimetidine pretreatment. The renal and biliary clearance of sulfisomidine were decreased significantly compared with those of control rabbits by cimetidine pretreatment. The results may be also related to the inhibition of sulfisomidine metabolism enzyme activity or reduction of blood flow in the liver.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.503-510
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• 1998

Effects of cadmium exposure on renal $Na^+$ and $K^+$ transports were studied in rats. During the course of cadmium treatment (2 mg Cd/kg/day, s.c. injections for 3 weeks) renal tubular transports of $Na^+$ and $K^+$ were evaluated by lithium clearance technique. During the early phase (first week) of cadmium treatment, urinary $Na^+$ excretion decreased drastically and this was due to an increased $Na^+$ reabsorption both in the proximal and distal nephrons. During the late phase (third week) of cadmium treatment, filtered $Na^+$ load was decreased by reduction in GFR, but the renal $Na^+$ excretion returned to the control level due to impaired $Na^+$ transport in the proximal tubule. Urinary excretion of $K^+$ did not change during the early phase, but it rose markedly during the late phase of cadmium treatment. These results indicate that a light cadmium intoxication induces a $Na^+$ retention, and a heavy intoxication results in a $K^+$ loss. Possible mechanisms for these changes are discussed.

• YAKHAK HOEJI
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• v.45 no.6
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• pp.683-693
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• 2001

This study was attempted to investigate the effect of raclopride, a dopamine $D_2$ receptor antagonist, on renal function in dog. Raclopride (70-220$\mu\textrm{g}$/kg), when given intravenously, Produced antidiuresis along with the decrease in free water clearance ( $C_{H_2O}$), urinary excretion of sodium and potassium ( $E_{Na}$ , $E_{K}$), partially decreased osmolar clearance ( $C_{osm}$) and increased reabsorption rates of sodium and potassium in renal tubules ( $R_{Na}$ , $R_{K}$). Raclopride administered into a renal artery did not influence on renal function in small doses (10 and 30$\mu\textrm{g}$/kg), whereas exhibited the decrease of urine volume (Vol) and $C_{H_2O}$ both in experimental and control kidney in much dose (100$\mu\textrm{g}$/kg), at this time, the decreased rates of both Vol. and $C_{H_2O}$) were more prominent in control kidney rather than that elicited in experimental kidney, and then only via was decreased in control kidney but increased in experimental kidney. Raclopride administered via carotid artery (30-200$\mu\textrm{g}$/kg) did not influence at all on renal function. Antidiuretic action induced by raclopride given intravenously was not affected by renal denervation. Raclopride given into carotid artery was little effect on renal function without relation to renal denervation. Above results suggest that raclopride produces antidiuresis by potentiation of antidiuretic hormone (ADH) action in blood without increase of ADH secretion in posterior pituitary gland, it is not related to renal nerve function in dogs.ogs.s.

• The Korean Journal of Pharmacology
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• v.7 no.1
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• pp.67-76
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• 1971

The excretion of uric acid in man has been of great interest because of its importance as an end product in purine metabolism as well as of its role in causing gout. There are many differences in the modes of renal handling of urate among various species of animals. Uric acid actively secreted by the renal tubules of most vertebrate including amphibians, reptiles, and birds. On the other hand, in most mammals net tubular reabsorption of urate appears to be occurred with some exception, such, as Dalmatian dog. In the rabbits, however, the mechanism of renal excretion of uric acid has long been a subject of controversial results. Within a given group it was possible to find individuals with either net secretion or net reabsorption of urate depend on the experimental conditions. Excretion of urate can be depressed or enhanced by a variety of drugs belonging mainly to the aromatic acid group. Diodrast, probenecid, cinchophen and salicylates have been reported as uricosuric agents, on the other hand, lactate, benzoate, pyrazinoic acid, acetazolamide and chlorothiazide are known to be contraindicated to use for the patient with gout since these agents depress the excretion of uric acid from the kidney. However, complex and sometimes the paradoxical effects on the urate excretion by those above mentioned drugs are not uncommon. The experiments were designed to investigate the mechanisms of renal handling of urate as well as the effects of variety of drugs on the tubular transport of uric acid in the rabbits. Male or female white rabbits, from 1.5 to 2.5 kg in weight, were used. The experimental methods used in these studies were clearance, stop-flow, and retrograde injection techniques. The effects of saline, salicylate, chlorothiazide and probenecid were investigated in each experimental conditions. Results of the experiments were summarized as follows; 1. In the rabbits, the rate of urate clearance was always lower than the rate of inulin clearance. The filtration fraction of the urate was one third on an average, therefore, it is estimated that approximately two thirds of filtered urate was reabsorbed. 2. In the kidneys of rabbits, the urate clearance was increased significantly by administration of chlorothiazide and decreased by probenecid. The administration of salicylate had no effect on the rate of urate clearance. The filtration fraction of urate was increased by chlorothiazide and decreased by probenecid. 3. In the stop-flow studies, the U/P ratio of urate was higher than the U/P ratio of inulin in the proximal region, indicating the secretion of uric acid in the proximal tubules. The proximal peak was increased by chlorothiazide and inhibited by probenecid.4. In the retrograde injection studies, the reabsorption of urate in the proximal region was observed, and these reabsorptive transport of urate was depressed by either probenecid or by chlorothiazide. 5. No distal tubular activity was observed under any of these experimental conditions concerning urate transport. The results of these experiments show that probenecid inhibits both secretory and reabsorptive transport of uric acid in the kidney of the rabbits. The enhancement of secretory transport of urate by chlorothiazide in the clearance study was due to the secondary action of chlorothiazide which inhibits the reabsorptive transport of urate in the proximal tubules. It is evident that the urate transport in the kidneys of rabbits is bidirectional nondiffusive flux both secretory and reabsorptive directions in the proximal tubules.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.151-159
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• 1993

Effect of yohimbine, a specific antagonist for presynaptic adrenoceptor, on the renal action of clonidine, a specific presynaptic adrenoceptor agonist, was investigated in dog. Clonidine, when given intravenously, produced diuretic action accompanied with augmentation of osmolar and free water clearance (Cosm and 4C_{H_2O}$), and elicited the increase of amounts of sodium and potassium excreted in urine ($E_{Na}\; and\; E_k$). These actions of clonidine were inhibited by yohimbine either injected intravenously or infused into a renal artery. Clonidine, when infused into a renal artery, produced antidiuretic action accompanied with decreased of glomerular filtration rate (GFR) and renal plasma flow (RPF), and exhibited the reduced amounts of sodium and potassium in urine. These actions of clonidine injected into a renal artery were blocked by yohimbine administered either into vein or into a renal artery. Above results suggest that yohimbine block the renal action of clonidine only in central system, do not in kidney.

• Biomolecules & Therapeutics
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• v.1 no.1
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• pp.84-92
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• 1993

This study was performed to elucidate the mechanism of antidiuretic action of diltiazem by infusion into the vein and carotid artery, of diuretic action into a renal artery in dog. Renal denervation caused a reversal of the effect of diltiazem from the antidiuretic to the diuretic when infused into vein or carotid artery, and potentiated the diuretic effect when infused into a renal artery. The changes of renal function in diuretic circumstances as described above included the increase in renal plasma flow, osmolar clearance, the amounts of sodium and potassium excreted in urine and the decrease in reabosrption rate of sodium and potassium in renal tubules. Above results suggest that antidiuretic action of diltiazem may be mediated by central nervous system, not by endogenous substance, diuretic action by direct renal action.

• YAKHAK HOEJI
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• v.36 no.1
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• pp.46-55
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• 1992

Methoxyverapamil, $Ca^{2+}$ channel blocker, when given intravenously by means of bolus, produced the transient increase of urine flow, and then methoxyverapamil was infused in this experiments. Methoxyverapamil, when infused into vein, elicited the increase of urine flow ancampanied with the increased glomeralar filtration rate(GFR), renal plasma flow(RPF), excretion amounts of sodium and potassium in urine($E_{Na},\;E_k$) and osmolar clearance(Cosm), wherease produced the no change of free water clearance($C_{H2O}$) and the reduction of reabsorption rates of sodium and potassium in reral tubules($R_{Na},\;R_k$). Methoxyverapamil, when infused into a renal artery, exhibited the diuretic action in only infused Kidney, at this time changes of renal function were the same aspect to that of intravenously infused methoxyverapamil. Methoxyverapamil, when infused into a carotid artery, exhibited the decreased urine flow along with the reduction of Cosm, $C_{H2O}\;and\;E_{Na}$. Above results suggest that methoxyverapamil possess both the diuretic action by direct action in kidney and antidiuretic action through the central function.

• Korean Journal of Clinical Pharmacy
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• v.8 no.1
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• pp.23-28
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• 1998

The pharmacokinetics of atenolol (25 mg/kg, i.v.) in the folate-induced renal failure rabbits was studied. Renal failure was induced by the i.v. injection of folate (50, 100, and 200 mg/kg). At folate dose of 100 and 200 mg/kg, the serum creatinine concentration (Scr) and blood urea nitrogen (BUN) increased significantly compared with control rabbits. Plasma concentrations and AUC of atenolol increased significantly at folate dose of 100 and 200 mg/kg. The elimination rate constant $(K_{el})$ and total body clearance $(CL_t)$ of atenolol decreased significantly, and half-life ($t_{1/2}$) and mean residence time (MRT) of atenolol increased significantly at folate dose of 100 and 200 mg/kg. The serum creatinine concentration $(S_{cr})$ correlated well (p<0.05) with half-life $(t_{1/2})$ and elimination rate constant $(K_{el})$ of atenolol, as well as BUN with AUC and total body clearance $(CL_t)$ of atenolol.

• Journal of Pharmaceutical Investigation
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• v.5 no.1
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• pp.28-40
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• 1975

Polyporus would used as diuretics. Then, for the purpose of experimentally certifying the above mention, the effect on the renal function of dog was investigated, utilizing clearance technique. Water and alcohol extracts, when injected intravenously, produced significant increases of urinary sodium and potassium, osmolar and free water clearances, and urine flow, while glomerular filtration rate and renal plasma flow remained unchanged. During diuresis produced by furosemide, addition of water extract reduced the action of furosemide and markedly renal plasma flow. It would appear that these compounds are capable of action by a different mechanism or a different site. water extract, when infused directly into a renal artery, reduced the urine flow of experimental kidney as well as renal plasma flow, and the contralateral kidney exhibited diuresis, whereas amounts of sodium and potassium excreted in urine increased on both kidney. It is surmised from those observations that Polyporus induces diuresis by inhibition the reabsorptive mechanism of renal tubules through some endogeneous humoral substances, in addition, directly reduces the renal plasma flow.