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At least 1,063 records · Page 59Linked to original sources
PubMed1989

[Role of prostanoids in the control of renal function in normal potassium balance and in acute experimental potassium depletion. 4. Relation of extrarenal parameters, renal function parameters and urinary excretion of prostanoids].

The renal function has been evaluated by clearance (cl.) method during hypotonic polyuria and successive moderate antidiuresis induced by a low dose of lysine-8-vasopressin; four 15 min and two 60 min cl. periods were performed, respectively. Glomerular filtration rate was estimated by creatinine cl.; the osmotic cl. (Cosm, CH2O), the absolute and fractional excretions of water, sodium, potassium and chloride were determined by usual methods. The urinary concentrations of PGE2, 6-keto-PGF1 alpha (6KPGF) and TxB2 were measured by RIA. The study protocol was applied in normal potassium balance and experimental potassium balance (KD), both in absence and presence of indomethacin. In KD groups with a potassium cumulative deficit of 198.4 +/- 22.2 meq (D3; n = 6) during polyuria significant correlations are consistent with the hypothesis that the lower the plasma potassium concentration is the higher the urinary chloride excretion and the inhibition of distal fractional chloride reabsorption. Moreover, by utilizing the polyuria and antidiuresis data pool, the effects of urine flow rate changes on PGE2 and 6KPGF urinary excretions are blunted as compared to normal potassium balance (n = 14). After indomethacin treatment (D3.I) the following functional relationships are disclosed: a) the lower the kaliemia is the lower the urinary chloride and potassium excretions and the higher the fractional isosmotic reabsorption; b) the lower the urinary potassium excretion is the lower the urinary chloride excretion. In both D3 and D3.I experimental groups the positive correlation between urinary chloride excretion and urinary potassium excretion is significant.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Effect of intravenous glucagon on the urinary excretion of adenosine 3',5'-monophosphate in man and in rats. Evidence for activation of renal adenylate cyclase and formation of nephrogenous cAMP.

To examine the effect of glucagon in vivo on renal formation and excretion of cAMP, clearance studies were performed in patients with hypoparathyroidism and in parathyroidectomized rats. Four patients with idiopathic hypoparathyroidism and 2 patients with pseudohypoparathyroidism were studied during an intravenous glucagon infusion (20 micrograms/kg body weight). In all patients, glucagon induced a significant increase in nephrogenous cAMP and a 2- to 3-fold increase in fractional excretion of phosphate. The average increase in nephrogenous cAMP was from a baseline of 784 +/- 229 to 18,748 +/- 3,842 pmol/100 ml glomerular filtrate (GF) (p less than 0.01) and occurred 30-60 min after the beginning of the glucagon infusion. The effect of intravenous glucagon, given as a bolus, was further examined in parathyroidectomized rats. Glucagon elicited a significant increase in the urinary excretion of the nucleotide. The excreted cAMP was compared with its filtered load for each urine collection period. In the first two collections, 0-15 and 15-30 min, the filtered load of cAMP was higher than its urinary excretion. During the following periods, 30-90 min, the excreted urinary cAMP exceeded by far its filtered load, suggesting a net nephrogenous contribution to the excretion of the nucleotide. Infusion of exogenous cAMP to parathyroidectomized rats induced significant increments in the filtered load and urinary excretion of the nucleotide. Tubular secretion of extrarenal cAMP could not be detected during the cAMP infusion. These results provide evidence supporting in vivo a possible parathyroid-independent formation of nephrogenous cAMP after glucagon administration, in men and in rats. The glucagon-induced increase in nephrogenous cAMP seems to account, at least partly, for some of the renal actions of this hormone.

Adenylyl Cyclases↗
PubMed1986

Urinary excretion and renal production of prostaglandins E2, F2 alpha, and thromboxane B2 in experimental diabetes mellitus.

To delineate the urinary excretion of prostaglandins E2 (PGE), F2 alpha (PGF), and thromboxane B2 (TxB) in diabetic rats, we treated male Sprague-Dawley rats with streptozocin 60 mg/kg or with vehicle. Plasma glucose and creatinine concentration and 24-hour urine collections for determination of TxB, PGE, PGF, creatinine, and protein excretion were measured at 2, 8, and 14 weeks after streptozocin. Creatinine clearance was significantly decreased in diabetic rats at 2 and 8 weeks, whereas the urinary protein excretion was three to five times that of control animals at all times. The 24-hour excretion of TxB was elevated twofold to threefold in diabetic rats, whereas PGE and PGF excretion were both significantly decreased. This alteration in excretion was not caused by increased urine flow rate, inasmuch as mannitol-induced osmotic diuresis caused an increase in PGE and PGF excretion. Eight weeks after streptozocin, a group of diabetic and control rats were sacrificed, and the production of PGE, PGF, and TxB by the renal papillae and glomeruli determined. An additional five diabetic rats were treated with protamine zinc insulin for 1 week before sacrifice to determine the effect of insulin treatment on the production of PGE, PGF, and TxB by the glomeruli and renal papillae. Papillary production of PGE, PGF, and TxB was decreased in diabetic rats, as was glomerular production of PGE and PGF. Insulin treatment increased PGF production by the renal papillae and increased PGE, PGF, and TxB production by glomeruli. These results indicate that changes in prostaglandin excretion accompany the development of marked proteinuria and a decrease in creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

[Urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and its isoenzyme B as a marker of the nephrotoxicity of gentamicin: re-test from an animal model].

A high level of NAG urinary excretion with marked isoenzyme B excretion are commonly considered as an indicator of aminoglycoside nephrotoxicity. The urinary excretion of NAG following gentamicin treatment was studied in rabbit. The rabbits received gentamicin at equivalent therapeutic (5 and 20 mg/kg/j) or toxic (50 mg/kg/j) doses during four days. Activities were measured daily and isoenzyme patterns were determined on the day of maximal urinary enzyme excretion. Isoenzyme patterns of kidney cortex, urinary control, and urinary gentamicin treated rabbits were compared. As compared with control rabbit, no changes in isoenzyme profiles appeared following the administration of gentamicin at 5-20 mg/kg/j. Thus, NAG enzymuria is constituted almost exclusively by isoenzyme A. Surprisingly, the high level of NAG excretion following the administration of gentamicin at 50 mg/kg/j is not accompanied by a marked excretion of isoenzyme B. The present results confirm controversy still exists regarding the clinical significance of urinary NAG excretion. These data indicate that increases in urinary NAG and isoenzyme B excretion following gentamicin treatment in Human are not always reliable indicators of renal tubular cell lysis.

Acetylglucosaminidase↗
PubMedDate not supplied

Effects of two different loading doses of L-tryptophan on the urinary excretion of tryptophan metabolites in rats, mice and guinea pigs. Correlation with the enzyme activities.

The effect of two different loading doses of L-tryptophan (0.5 and 1.0 g/Kg b.w.) on excretion of tryptophan metabolites and the relation to the enzyme activities were studied in rats, mice and guinea pigs. In rats there is no ratio between the dosage used and the levels of the metabolites excreted. Doubling the amount of tryptophan administered, a 5-fold increase in the elimination of the metabolites along the kynurenine pathway is obtained. The 1.0 g/Kg load provides a more complete pattern of the metabolites than with the 0.5 g/Kg b.w. load. Kynurenic acid, kynurenine and xanthurenic acid are the chief metabolites excreted. In mice, the urinary excretion of the metabolites is very low with both loads. In guinea pigs, xanthurenic acid is excreted in the highest amount and kynurenic acid and kynurenine also constitute the large fractions with both loadings. The load of 0.5 g/Kg b.w. is preferable to that of 1.0 g/Kg b.w. for not causing B6-deficiency. Liver tryptophan pyrrolase exists in two forms in rats, while in mice and in guinea pigs it is present only as holoenzyme. This enzyme is more active in rats than in the other two species of animals. Kynureninase activity is lower in guinea pigs, but it apparently correlated to the low levels of excretion of the metabolites following this step. Kynurenine aminotransferase is very active in rats and in mice, while it is apparently depressed in guinea pigs, in contrast with the high excretion of xanthurenic and kynurenic acids, that puts in evidence a B6-deficiency. The excretion of tryptophan metabolites and enzyme activities are better correlated in rats.

Animals↗
PubMed1986

[Technics for the study of the renal excretion of free water in normal rats and those with experimental liver cirrhosis].

Different techniques to measure free water excretion in rats, administered an oral water overload and with measurement of its ability to excrete it into the urine have been studied. When 30 or 50 ml/kg b.wt. were administered and the urine excreted in 3 h was collected, a decrease on the urinary osmolality (UOSM) was observed with respect to the baseline UOSM, which was similar in both overloads, although the percentage of the overload excreted was significantly greater with 50 ml/kg. However, the UOSM obtained was hypertonic as compared to plasma osmolality (POSM) indicating that this determination was not useful to study free water excretion. In a further study it was investigated if there was any period of time in which all the animals excreted hypotonic urine. However, results indicated that the period for excreting a maximally diluted urine was very variable in time. The best technique to study free water excretion in these animals was the collection of each spontaneously voided urine independently, to measure the minimal UOSM. When a 50 ml/kg water load was administered and the minimal UOSM was determined it was observed to be lower than POSM in all the animals indicating that this technique was useful to study this derangement in these animals.

Animals↗
PubMed1986

[Studies on absorption, distribution and excretion of 14C labeled pivaloyloxymethyl (+)-(6R,7R)- 7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]- 3-[(5-methyl-2H-tetrazol-2-yl)methyl]-8-oxo-5-thia- 1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate (14C-T-2588) in rats and mice].

Absorption, distribution and excretion of T-2588 were studied in rats and mice using (aminothiazole-2-14C) T-2588 and (pivaloyloxymethyl-14C) T-2588. Results are summarized below. The binding rate of 14C-T-2525, an activated form of 14C-T-2588 in vivo, to serum protein was 90 approximately 100% in rats and mice after an oral administration of (aminothiazole-2-14C) T-2588. Blood levels of radioactivity reached to the highest concentration at 1 hour after an oral administration of (aminothiazole-2-14C) T-2588 to rats, and then gradually diminished. After an oral administration of (aminothiazole-2-14C) T-2588 to rats and mice, the highest radioactivity distribution was found in kidney among all the organs except stomach, intestine and bladder. Radioactivity was widely distributed into other organs such as adrenal, lung, liver, heart and pancreas. But little radioactivity was found in the brain. In new born rats, tissue levels of radioactivity were lower and diminished slower than those of adult rats. After an oral administration of (aminothiazole-2-14C) T-2588 to rats and mice, urinary excretion of radioactivity was about 26% and 35% of the dosed radioactivity in rats and mice, respectively, and fecal excretion was about 76% and 63% of the dosed radioactivity in rats and mice, respectively. Urinary and fecal excretion patterns of radioactivity after multiple oral administration of (aminothiazole-2-14C) T-2588 for 7 days to mice were similar to those after a single administration. This result suggests that T-2588 did not accumulate in the body. After an oral administration of (pivaloyloxymethyl-14C) T-2588 to rats and mice, urinary excretion was both about 8% of the dosed radioactivity, and fecal excretion was both about 6%. Then excretion of 14CO2 into respiratory air was about 55% and 66% of the dosed radioactivity in rats and mice, respectively. Biliary excretion was about 6.5% of the dosed radioactivity after an oral administration of (aminothiazole-2-14C) T-2588 to rats. Small amount of radioactivity was secreted to the milk after intravenous administration of (aminothiazole-2-14C) T-2525 to nursing rats. After an administration of (aminothiazole-2-14C) T-2588 to pregnant mice, radioactivity hardly transferred into the fetus.

Administration, Oral↗
PubMed1986

The influence of diuretics on the excretion and metabolism of doping agents. III. Etilamfetamine.

The urinary excretion of etilamfetamine (ethylamphetamine) and its major metabolite amphetamine in humans was followed over a period of several days after the oral administration of two formulations. The excretion of both substances was affected by urinary pH. Excretion peaks were observed 3-4 h after the ingestion of etilamfetamine in a capsule and the proportion of etilamfetamine excreted during 72 h was 22.2 to 54.4%. Excepting a shift in the peak excretion time to 4-5 h, no meaningful pharmacokinetic differences were found when Apetinil-Depot, a retard formulation, was administered. The intake of acetozolamide shortly after etilamfetamine resulted in a decrease of the etilamfetamine excretion during one day and a suppression below the detection limit for periods varying from 2-7 h post-dosing. Although the etilamfetamine excretion was suppressed from 2 to at least 10 h post-dosing, the action of the diuretic clofenamide on the etilamfetamine excretion is generally not so obvious as that of acetazolamide. The administration of furosemide only reduced the etilamfetamine concentrations by a factor of 4 to 5 during a 2-h period.

Acetazolamide↗
PubMed1985

Acute changes of iodothyronine excretion by bile after a single and repeated administration of dexamethasone in rats.

Bile was collected from cannulated bile duct under pentobarbiturate anesthesia and the excretion of several iodothyronines was estimated with the aid of radioimmunoassay as described previously. The excretion of triiodothyronine (T3) was significantly decreased between 4 and 6 h after a single injection of 20 and 40 mg kg-1 dexamethasone (DEX), while no changes in the excretion of thyroxine (T4) and reverse triiodothyronine (rT3) were found. In another experiment a decrease of T3 excretion was observed together with an increase of rT3 excretion and of T4/T3 and rT3/T3 ratio between 9 and 11 h after a single injection of 0.75, 1.5 and 3.0 mg kg-1 DEX, the differences being in most cases significant as compared to controls. In the same experiments a dose related increase of excretion of 3,3'-diiodothyronine (3,3'-T2) and 3,5-diiodothyronine (3,5-T2) was found, while the excretion of 3',5'-diiodothyronine (3',5'-T2) decreased with dose of DEX. Similar results were observed even after the administration of 1.5 and 3.0 mg kg-1 DEX for 5 days. In addition, the level of rT3 in serum was significantly increased at 9 h after a single dose of 3.0 mg kg-1 DEX and after 5 days administration of 1.5 and 3.0 mg kg-1 DEX. The data support a previous view that the changes in biliary excretion of iodothyronines are closely related to deiodinating metabolism of T4 in the liver and are expressed earlier and more remarkably than these in their plasma level.

Animals↗
PubMed1985

The effect of dietary sodium loading on the kinetics of sodium excretion and blood pressure regulation in essential hypertensive men.

The kinetics of urinary sodium excretion defined as the rate of urinary sodium excretion during five-days oral sodium loading was investigated in 12 male patients with essential hypertension. The change in blood pressure under oral 200 mmol/24 h NaCl intake correlated inversely with the rate of urinary sodium excretion (r = -0.60, p less than 0.05), but did not significantly depend on the change in the absolute amount of excreted sodium. The rate of sodium excretion correlated directly with preload glomerular filtration rate (GFR) (r = 0.63, p less than 0.05), effective renal plasma flow (ERPF) (r = 0.78, p less than 0.01) and inversely with renal vascular resistance (RVR) (r = 0.67, p less than 0.01). The fall of renal plasma flow at moderate increment in the filtration fraction under sodium loading correlated directly with the rate of urinary sodium excretion (r = 0.73, p less than 0.01). The results suggest that: 1) the rate of sodium excretion is a more important factor in blood pressure regulation than the ability of the kidney to excrete the entire sodium load; 2) renal haemodynamics plays an indirect role in blood pressure regulation.

Adult↗
PubMed1979

Changes in connective tissue metabolism due to bone fractures in children aged 10--14 years. III. Urinary hydroxyproline and glycosaminoglycan excretion following bone fractures treated in different ways.

Urinary hydroxyproline and glycosaminoglycan excretion was studied in the course of fracture healing in twenty 10--14-year-old children with fracture of the femur or of the tibia and fibula. In 11 children reduction and plaster cast were used, in 5 osteosynthesis, and in 4 extension of 6--21 days duration combined with immobilization by plaster cast. In the state of resorption, an increase was observed in the urinary excretion of hydroxyproline and total glycosaminoglycans and in the six glycosaminoglycan fractions studied. As a result of the soft tissue damage accompanying the fracture, the excretion of hyaluronic acid, heparan sulphate, and dermatan sulphate showed the most marked increase. No statistically significant relationship could be demonstrated between the mode of treatment and the amounts of urinary hydroxyproline and glycosaminoglycan, but the stage of resorption was prolonged in the case of treatment with traction. At the beginning of regeneration, a decrease in hydroxyproline excretion and then an increase corresponding to the intensive synthesis of collagen were demonstrated. Glycosaminoglycan excretion during the development of fibrous callus was considerably below the control value. Excretion of the metabolites decreased markedly in the five operated patients. in the case of extension, the stage of regeneration prolonged by 4 to 10 days. In the stage of calcification, urinary hydroxyproline excretion was increased while the excretion of glycosaminoglycan and its fractions was the same as in the controls except in the patients treated with traction. No statistically significant relationship was found between the urinary amounts of hydroxyproline and glycosaminoglycan and the mode of treatment. In the case of traction, fracture repair and the formation of connective tissue callus were prolonged.

Adolescent↗
PubMedDate not supplied

Metabolism and excretion of 2,4-dinitrotoluene in male and female Fischer 344 rats after different doses.

Female Fischer 344 rats are less susceptible to the hepatocarcinogenic effects of 2,4-dinitrotoluene (2,4-DNT) than males. This study is a comparison of the metabolism and excretion of 2,4-DNT in male and female rats after oral doses of 10, 35, or 100 mg of 14C-2,4-DNT per kg. The major route of elimination of 14C after all doses was the urine. 4-(N-Acetyl)amino-2-nitrobenzoic acid (4Ac2NBAcid), 2,4-dinitrobenzoic acid (2,4-DNMBAcid), 2-amino-4-nitrobenzoic acid (2A4NBAcid), and 2,4-dinitrobenzyl alcohol glucuronide (2,4-DNBAlcG) were identified in urine of rats. These four compounds accounted for greater than 85% of the radioactivity excreted in urine. Female rats excreted a significantly greater percentage of the dose in the urine as 2,4-DNBAlcG at doses of 10 or 35 mg/kg when compared to males. Both sexes showed dose-dependent changes in urinary excretion of 2,4-DNT metabolites. Males excreted a smaller percentage of the dose as 2,4-DNBAcid at 100 mg/kg than at 10 or 35 mg/kg. Females excreted less of the dose as 2,4-DNBAcid and 2,4-DNBAlcG at 100 mg/kg than at 10 or 35 mg/kg. The only sex difference in 2,4-DNT metabolism or excretion of sufficient magnitude to account for the sex difference in susceptibility to the hepatocarcinogenic effects of 2,4-DNT was the greater percentage of 2,4-DNT excreted as 2,4-DNBAlcG by female rats at 10 or 35 mg/kg.

Animals↗
PubMedDate not supplied

The metabolism and excretion of mononitrotoluenes by Fischer 344 rats.

The metabolism and excretion of 2-, 3-, and 4-nitrotoluene (2NT, 3NT, and 4NT, respectively) were studied in male Fischer 344 rats. Excreta were collected for 72 hr after an oral dose (200 mg/kg) of radiolabeled 2NT, 3NT, or 4NT. Radiolabel from each NT isomer was rapidly excreted (86, 73 and 74% of the dose for 2NT, 3NT, and 4NT, respectively in 24 hr). The urine was the major route of excretion with 70-85% of the dose being excreted by that route in 72 hr. Five to 13% and 0.0 to 0.1% of the dose was excreted in the feces and expired air, respectively, in 72 hr. The major metabolites excreted in urine in 72 hr after administration of 2NT were 2-nitrobenzoic acid (29% of the dose), an unidentified metabolite (16% of the dose), 2-nitrobenzyl glucuronide (14% of the dose), and S-(2-nitrobenzyl)-N-acetylcysteine (12% of the dose). The major metabolites excreted in urine in 72 hr after administration of 3NT were 3-nitrohippuric acid (24% of the dose), 3-nitrobenzoic acid (21% of the dose), and 3-acetamidobenzoic acid (12% of the dose). The major metabolites excreted in urine in 72 hr after administration of 4NT were 4-nitrobenzoic acid (28% of the dose), 4-acetamidobenzoic acid (27% of the dose), and 4-nitrohippuric acid (13% of the dose). Thus, the major urinary metabolites of 3NT and 4NT differed only quantitatively while those of 2NT were also qualitatively different.

Animals↗
PubMed1982

Excretion of attenuated polioviruses in children vaccinated with live oral poliovirus vaccine.

The excretion of attenuated polioviruses was studied in a group of nursery children vaccinated with 105TCD50 of each type of virus. The primovaccinated children were found to excrete type 1 poliovirus for 8 weeks, type 2 for 11 weeks after the vaccination with the type 1 + 2 bivaccine. Poliovirus type 1 as eliminated by 78% and type 2 by 98% of the vaccinees. The separately administered type 3 was detectable for 6 weeks and was isolated from 100% of the vaccinees. The highest per cent of children with type 1 excretion positivity was recorded at week 5, with type 2 positivity at week 1 and with type 3 positivity at week 2. The poliovirus excretion peaked early after the vaccination, the titres of the poliovirus type 2 were the highest. The children revaccinated next year with the type 1 + 2 bivaccine eliminated the respective types of virus 1 - 2 weeks; type 3 poliovirus was detectable for 6 weeks after revaccination and was excreted by the highest per cent of vaccines. The contact infections caused by the attenuated polioviruses developed in 9 from 22 children vaccinated previously. The excretion of polioviruses did not last longer than 1 week. The contact infections were most frequently caused by the poliovirus type 2. The examined children, particularly those vaccinated previously, turned out to excrete also other enteroviruses identified as Coxsakieviruses B 4 and B 5 and Echovirus 21. In the primovaccinated these viruses were isolated only from those with the negative excretion of polioviruses.

Child, Preschool↗
PubMed1978

[Disorder in the circladian rhythms of calcium, magnesium and phosphorus excretion in hypertension (use of the "cosinor" method)].

The daily rhythms of calcium, magnesium, and phosphorus excretion were studied in 10 healthy individuals and in 43 patients with hypertensive disease. All the subjects under study followed the standard regimen of wakefulness, sleep, and meals. The transverse "cosinor" method of rhythm study was used. Statistically significant daily rhythms of calcium, magnesium, and phosphorus excretion were revealed in healthy individuals, in which case the phenomena of internal synchronization were encountered. Daily rhythms of phosphorus and calcium excretion were revealed in patients with stage IB hypertensive disease, while the rhythm of magnesium excretion was statistically insignificant. In stage IIA the rhythms of calcium, magnesium, and phosphorus excretion are demonstrated, but desyncronization as compared to the findings in healthy individuals is observed. There are no statistically significant daily rhythms of calcium, magnesium, and phosphorus excretion in patients with stages IIB and III hypertensive disease. The change in the rhythm of magnesium excretion in patients suffering from IB stage hypertensive disease points to the early inclusion of the disturbance of its homeostasis in the development of this disease. The control mechanisms of the daily rhythms of calcium, magnesium, and phosphorus excretion are not clear to date. The study of the daily rhythms of these elements is nevertheless of definite importance in revealing disturbances in their homeostasis.

Adult↗
PubMed1984

Effect of gastrointestinal surgery and bacterial overgrowth on the urinary excretion of sulfur amino acids and their main degradation products.

The urinary excretion of sulfur amino acids and their main degradation products was determined in patients subjected to various forms of gastrointestinal surgery or with bacterial overgrowth. A normal excretion of total sulfur and inorganic sulfate was found, indicating an adequate intake and maintained ability to absorb sulfur amino acids. An increased excretion of ester sulfate was observed in all groups except patients subjected to ileocecal resection or proctocolectomy, probably owing to bacterial overgrowth. A reduced excretion of methionine was observed in patients with gastric resection (Billroth I), ileocecal resection, and abnormal gut flora, whereas patients with jejunoileal bypass showed an increased excretion of methionine, probably a consequence of the impaired liver function. For cystathionine, a similar effect was found in patients with ileocecal resection and jejunoileal bypass. A reduced excretion of mercaptolactate was found in jejunoileal bypass patients. A low excretion of thiosulfate was seen in proctocolectomized patients, suggesting that the bacterial flora of the colon plays a role in the formation of thiosulfate. A low excretion of thiocyanate was found in gastric-resected patients, which may be due to a decreased ability to hydrolyze cyanogenic and/or thiocyanogenic glycosides or to a reduced intake of these compounds.

Adult↗
PubMed1984

Residual chloroquine and metabolites in man as a sequel of previous chloroquine medications: a urinary excretion study and its significance.

In malaria-endemic areas like Nigeria, chloroquine is used frequently and extensively in the management of attacks. In this investigation urine samples of six different adult subjects showed a significantly wide range of excretion of total chloroquine and metabolites (10.01 to 0.021 mg) in 12 h due to residual levels of the drug in the subjects as a function of time of last medication with the drug. Two subjects representing extreme users of the drug--a naive subject and a frequent user--were given 300 mg of chloroquine each and the excretion rate profile monitored for 24 h. The first-time user of chloroquine showed a typical cumulative excretion pattern with total excretion of 16 mg while the frequent user showed a bimodal cumulative excretion curve with the second phase tending to a higher plateau effect and a total excretion of 21 mg in 24 h. These different levels of total excretion could be attributed to the influence of protein binding and tissue accumulation of the drug in the frequent user, and a second-phase excretion related to release of some bound chloroquine and metabolites. These effects are considered in relation to accumulation of chloroquine in the body resulting from frequent medication with the drug. Information regarding the time of last medication, and residual levels of chloroquine and metabolites is necessary for instituting the appropriate therapeutic regimen. The assay techniques involving single selective solvent extraction, thin-layer chromatography and spectrophotometric measurements, have been found adequately quantitative, simple and quick for use in routine clinical laboratory investigation.

Adult↗
PubMed1983

The effect of taurocholate on canine bile flow, biliary excretion and concentration of ioglycamide.

The bile acid taurocholate increases the biliary excretion of organic anions, such as sulfobromophthalein (BSP), bilirubin and iopanoic acid. In the present study has been investigated the effect of taurocholate on 1. Canine biliary excretion and concentration of the i.v. contrast medium ioglycamide and 2. Canine bile flow. The experimental model consisted of cholecystectomized, anaesthetized dogs with a fistula, through which the common bile duct could be catheterized and drained. One hour after cannulation, i.v. infusion of ioglycamide at a rate of 4 mumol/min./kg. was started. Two hours after the infusion start a control group received i.v. infusion of saline, while in another a 1.5% sodium taurocholate infusion was started with stepwise increases with 30 min. intervals from 0.4 to 0.8, 1.6 and 3.2 mumol/min./kg. Compared with control, all rates of taurocholate infusion increased bile flow and decreased biliary ioglycamide concentration. Although the bile flow with increasing taurocholate infusion rates was enhanced, the biliary ioglycamide excretion did not increase. The results indicate that ioglycamide and taurocholate are excreted into bile by separate excretion mechanisms. As taurocholate increases the biliary excretion of some other organic anions, it supports the hypothesis that organic anions are excreted into bile by more than two excretion mechanisms, taurocholate affecting only some of them.

Animals↗