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PubMed1979

Plasma and urinary levels of triamterene and certain metabolites after oral administration to man.

The plasma and urinary levels of triamterene and two metabolites were measured using a specific method of analysis. Urinary excretion was completed after 48 h, which permitted a rough estimate of its half-life as longer than two hours. The areas under the curve were 672.5 +/- 160.3 and 1.311.3 +/- 399.1 micrograms/ml X h after the triamterene 150 mg and 300 mg p.o., respectively and correspondingly 4.2 +/- 1.4% and 3.7 +/- 0.6% of the dose were excreted as unchanged drug. The principal metabolite of triamterene found was the sulfate conjugate. The area under the curve of this metabolite amounted to 6.672 +/- 2.120 and 11.941 +/- 5.005 micrograms/ml X h after the of 150 mg and 300 mg triamterene doses, respectively. The urinary excretion of the metabolite varied between 25.0 +/- 4.0% and 17.5 +/- 3.5% of the dose after either dose. In healthy subjects an effect on sodium excretion was observed after a dose of 150 mg, whereas the potassium-retaining effect was observed only after the dose of 300 mg.

Administration, Oral↗
PubMed1982

Fluctuation analysis of short-circuit current in a warm-blooded sodium-retaining epithelium: site current, density, and interaction with triamterene.

Density and conductance of the Na-site in hen coprodeum were studied by employing fluctuation analysis of short-circuit current at sodium concentrations from 26 to 130 mM. Fluctuations of current in the frequency range 2-800 Hz were induced by triamterene, a reversible blocker of conducting epithelial Na-sites. At 130 mM Na the site density was 5.8 +/- 1.0 micrometer-2 and the site conductance was 4 pS. This conductance is equal to that of the frog skin (W. Van Driessche and B. Lindemann, 1979, Nature (London) 282:519-520). Extrapolation of site density to zero sodium renders a total of 38 +/- 28 sites micrometer-2, which is compared with other estimates for the coprodeum. The site-triamterene association and dissociation constants were 9.5 +/- 0.4 rad sec-1 micrometer-1 and 255 +/- 20 rad sec-1 and they were independent of external sodium concentration. An analysis of the affinity constant for triamterene based on the DC-short-circuit current was found to be unrelated to the external sodium concentration and identical to that obtained from fluctuation analysis indicating a noncompetitive interaction between sodium and triamterene. Due to the oxygen demand of the epithelium we have developed an experimental method using short data processing times. A new analytical approach using integration of the power density spectrum proved necessary because of low signal-to-noise ratios.

Animals↗
PubMed1989

Monitoring the effect of triamterene and hydrochlorothiazide on dihydrofolate reductase activity using a new spectrophotometric method.

A new spectrophotometric method is developed and applied for the study of the inhibitory effect of triamterene, hydrochlorothiazide and their combinations on the in vitro activity of dihydrofolate reductase enzyme. The method is based on incubating the drug (0.1-1.0 microM) or a buffer control with a solution containing reduced nicotinamide adenine dinucleotide phosphate (0.5 mM), magnesium chloride (1.29 mM), and folic acid as a substrate (0.01-0.1 mM) with the dihydrofolate reductase (0.25 unit). The resulting tetrahydrofolic acid is determined by first hydrolysing it by a methanol-hydrochloric acid mixture to produce p-aminobenzoyl glutamic acid, then adding p-dimethylaminocinnamic aldehyde reagent to form a stable pink coloured product. The colour is found to develop within 5 min and is stable over 12 h, with a maximum absorption at 545 nm. A linear calibration curve is formed by using standard solutions of tetrahydrofolic acid. The presence of the studied drugs did not interfere with the determination. Lineweaver-Burk plots of the reaction kinetics, in the presence of triamterene and/or hydrochlorothiazide showed a competitive inhibition of the dihydrofolate reductase in the presence of triamterene with or without hydrochlorothiazide. A 100% inhibition is obtained by 1 microM solution of triamterene at a folic acid concentration of 0.01 mM. No measurable effect of hydrochlorothiazide at the studied concentration range is demonstrated.

Folic Acid Antagonists↗
PubMed1981

Triamterene nephrolithiasis complicating dyazide therapy.

A case of triamterene nephrolithiasis is reported in a man after 4 years of hydrochlorothiazide-triamterene therapy for hypertension. The stone passed spontaneously and was found to contain a triamterene metabolite admixed with uric acid salts. Factors affecting triamterene nephrolithiasis are discussed and 2 previously reported cases are reviewed.

Drug Combinations↗
PubMed1985

Effects of triamterene and amiloride on urinary sediment in hypertensive patients taking hydrochlorothiazide.

In a crossover study of 26 hypertensive patients, the effects of triamterene (50 mg/day) and amiloride (5 mg/day) on urinary sediment were compared. Each drug was given for one month and all patients also received hydrochlorothiazide (50 mg/day). An abnormal urinary sediment--evident grossly as a reddish-brown precipitate after routine staining procedures and microscopically as characteristic reddish-brown crystals and casts, as previously described--was identified in 14 of 26 (54%) triamterene urine samples but in none of the amiloride samples. Results of renal function tests were similar for both drugs. In a clinic population of more than 1000 hypertensive patients over 4 years, interstitial nephritis was diagnosed in 4, all of whom were taking a triamterene-containing combination diuretic. It is possible that triamterene is a factor in the aetiology of interstitial nephritis.

Amiloride↗
PubMed2002

Determination of triamterene and leucovorin in biological fluids by UV derivative-spectrophotometry and partial least-squares (PLS-1) calibration.

The resolution of binary mixtures of triamterene (TAT) and leucovorin (LV) by application of first-derivative spectrophotometry and by application of Partial Least Squares calibration (PLS-1) was performed. Triamterene is determined in presence of leucovorin directly in the absorption spectra at 358 nm, and leucovorin is determined in the first-derivative spectra at 305.6 nm, zero-crossing of the triamterene. The mean recovery values in urine samples were 102 and 97% for TAT and LV, respectively. Partial Least Squares calibration (PLS-1) multivariate calibration of spectrophotometric data, have been applied to the determination of these compounds in serum and in urine without pretreatment of the samples. The absorption spectra of samples of serum or urine, spiked with triamterene and/or leucovorin, were used to perform the optimization of the calibration matrices by PLS-1 method. Mean recovery values were of 107 and 108% for TAT and LV in serum samples, and 98 and 91% for TAT and LV in urine samples.

Calibration↗
PubMed2002

Determination of triamterene by transitory retention in a continuous flow solid phase system with fluorimetric transduction.

A rapid and simple flow-through solid phase espectrofluorimetric system (sensor) is described in this paper for the determination of the diuretic triamterene at ng ml(-1) level in physiological fluids and in pharmaceuticals. This sensor is based on the transitory retention of the analyte on the cationic ion-exchanger gel Sephadex SP C-25 placed into a quartz flow-cell in the detection zone itself of a spectrofluorimeter and the continuous monitorization of its intrinsic fluorescence. The spectrofluorimeter was tuned at 240 (excitation) and 440 nm (emission). A transitory signal was obtained because the carrier solution used also eluted the analyte from the sensing zone and no derivatization reactions were needed. Triamterene could be determined in the concentration ranges of 10-400 and 2.5-80 ng ml(-1) with detection limits of 0.95 and 0.17 ng ml(-1) for 300 and 1000 microl of sample volume, respectively. The relative standard deviations (RSD) for ten independent determinations and at three concentration levels of standards solutions were lower than 0.90 for 300 microl and 0.45 for 1000 microl. The RSDs for the determination of triamterene in serum samples and pharmaceuticals were lower than 3.3 and 2.6%, respectively. The method was satisfactorily applied to the determination of triamterene in human serum and pharmaceuticals.

Calibration↗
PubMed2003

Direct determination of triamterene by potentiometry using a coated wire selective electrode.

A coated wire triamterene-selective electrode based on the incorporation of a triamterene-tetraphenylborate ion-pair in a poly(vinylchloride) coating membrane was constructed. The influence of membrane composition, temperature, pH of the test solution, and foreign ions on the electrode performance were investigated. The electrode showed a Nernstian response over a triamterene concentration range from 1.0 x 10(-6) to 3.5 x 10(-2) M, at 25 degrees C, and was found to be very selective, precise, and usable within the pH range 4.5-7.5. The standard electrode potentials, E degrees, were determined at 15, 20, 25, 30, 35, 40 and 45 degrees C and used to calculate the isothermal temperature coefficient (dE degrees /dt) of the electrode. Temperatures higher than 45 degrees C seriously affected the electrode performance. The electrode was successfully applied to the potentiometric determination of triamterene hydrochloride both in pure solutions and in pharmaceutical preparations.

Ion-Selective Electrodes↗
PubMed1979

[Severe megaloblastic anaemia by triamterene in a patient with alcoholic liver cirrhosis (author's transl)].

Mucosal ulceration and severe bone-marrow insufficiency with marked megaloblastic transformation occurred during treatment with triamterene in a patient with decompensated alcoholic liver cirrhosis and malnutrition. When the triamterene-containing preparation was stopped and folinic acid administered the haematological picture improved, but the patient died, with signs of hepatocellular insufficiency, of gastro-intestinal bleeding. The serum folic-acid level was markedly reduced due to the chronic malnutrition, while the vitamin B12 level was within normal limits. This observation indicates that when the pool of folic-acid coenzymes is reduced, triamterene can cause megaloblastic anaemia due to its folic-acid antagonism. Triamterene should, therefore, be given to patients with borderline folic-acid reservoirs, chronic alcoholism or during pregnancy, only under careful serial control of the blood picture.

Anemia, Macrocytic↗
PubMed1977

[Triamterene in the treatment of hypertension with hydrochlorothiazide and propranolol (author's transl)].

In 36 patients with essential hypertension the action and side effects of hydrochlorothiazide (25 mg/d), hydrochlorothiazide-triamterene (25 and 50 mg/d) and propranolol (160 mg/d) were investigated. Hydrochlorothiazide and hydrochlorothiazide-triamterene led to an average decrease of the systolic blood pressure by 21 and 30 mm Hg and of the diastolic pressure by 11 and 18 mm Hg. Propranolol alone decreased the systolic pressure by 35 mm Hg on average in 8 out of 16 patients. The diastolic pressure was lowered by 20 mm Hg. In the remaining 8 patients the systolic pressure, when propranolol was used alone, decreased by 21.3 mm Hg, the diastolic pressure by 11.3 mm Hg. Addition of hydrochlorothiazide-triamterene lowered pressures by a further 22.5 (systolic) and 10.6 (diastolic) mm Hg. No disturbances of the potassium or acid-base balance were observed using hydrochlorothiazide-triamterene.

Acid-Base Equilibrium↗
PubMed1977

[Serum and total body potassium during treatment with chlortalidone and hydrochlorothiazide. Influence of triamterene (author's transl)].

The serum and total body potassium was investigated in 25 patients with non-congestive cardaic failure before and during saluretic treatment. Treatment with triamterene (100 mg/d; n = 10) over a period of 3 weeks led to an increase of serum potassium (from 4.1 +/- 0.65 to 4.7 +/- 0.51 mmol/l) and of total body potassium (by 110 mmol). After treatment with chlortalidon for 7 days (100 mg/d; n = 6) serum potassium concentration decreased from 4.38 "/- 0.37 to 3.30 +/- 0.46 mmol/l (approximately 25%). The total body potassium decreased by 240 mmol (approximately 10%). Continuation of the treatment with a combination of chlortalidon (50 mg/d) and triamterene (150 mg/d) led to correction of the extra- and intracellular potassium loss after 1 to 2 weeks. No significant change of serum and total body potassium was found during and after 6 months of treatment with hydrochlorothiazide (50 mg/d) and triamterene (100 mg/d; n = 9). The results demonstrate the potassium loss which occurs in the early stage of saluretic treatment and show the antikaluretic potency of triamterene.

Adult↗
PubMed1985

[Diuretic monotherapy in heart failure. Comparison of piretanide and hydrochlorothiazide-triamterene].

The effects of piretanide and a hydrochlorothiazide (HCT)-triamterene combination were compared in an open, controlled, randomised study on two groups of 15 patients, aged 42-74 years, with congestive heart failure (NYHA II-III). Weight loss was significant in both groups (P less than 0.05). At the end of the 14 day investigation ten patients from the piretanide group but only four patients from the HCT-triamterene group were fully recompensated. The left ventricular end-systolic and end-diastolic diameters were significantly less under piretanide (P less than 0.05 and P less than 0.01, respectively) than under HCT-triamterene. The shortening fraction and the circumferential velocity of shortening under piretanide increased by 25% over the initial value (P less than 0.001) whereas HCT-triamterene produced no change. A small but statistically significant (P less than 0.05) fall in serum potassium as well as a rise in urinary potassium, sodium and chloride concentration occurred with piretanide.

Adult↗
PubMedDate not supplied

The identification and quantitation of triamterene in blood and urine from a fatal aircraft accident victim.

Triamterene, a diuretic drug used in combination with other drugs for the treatment of hypertension, was found in the blood and urine of a fatal aircraft accident victim. The extraction and identification of triamterene is difficult. It exhibits poor extraction efficiency using some standard base-extraction procedures, and the parent drug is unsuitable for analysis using gas chromatography. In this case, a thin-layer chromatography solvent system and high-performance liquid chromatography were used to identify and quantitate triamterene in blood and urine. Triamterene is a strong absorber in the ultraviolet region and has an unusual UV spectrum, which simplifies the identification and quantitation of this substance by high-performance liquid chromatography.

Accidents, Aviation↗
PubMed1996

Triamterene suppresses bombesin-enhanced peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane.

The effects of combined administration of bombesin and the diuretic triamterene on the incidence of peritoneal metastasis of intestinal cancers induced by azoxymethane (AOM) and the labeling index of intestinal cancers were investigated in male inbred Wistar rats. From the start of the experiment, rats were given weekly s.c. injections of AOM (7.4 mg/kg body weight) for 10 weeks and s.c. injections of bombesin (40 micrograms/kg body weight) every other day, and from week 16, s.c. injections of triamterene (10 and 20 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal cancers. Although administration of both doses of triamterene with bombesin had little or no influence on the enhancement of intestinal carcinogenesis by bombesin, or the location, histologic type, depth of invasion, or labeling index of intestinal cancers, it significantly reduced the incidence of cancer metastasis. These findings indicate that triamterene suppresses cancer metastasis through a mechanism that does not affect the proliferation of intestinal cancers.

Adenocarcinoma↗
PubMed1982

Relative potency of spironolactone, triamterene and potassium chloride in thiazide-induced hypokalaemia.

1 The influence of spironolactone 50 mg and 100 mg daily, triamterene 100 mg and 200 mg daily, potassium chloride 32 mmol and 64 mmol daily and placebo on plasma potassium and other variables was examined in a random crossover study of nine hypertensive patients taking bendrofluazide 10 mg daily. 2 Spironolactone and triamterene had significant and parallel dose-response curves for plasma potassium, with a relative potency for triamterene:spironolactone of 0.25:1, significantly lower than the accepted 0.5:1 ratio. These drugs also lowered serum sodium, bicarbonate and body weight, and increased serum urea and creatinine. 3 Potassium chloride increased plasma potassium above placebo values, but the dose-response was not significant and was not parallel with those of the potassium-sparing drugs. Seven of nine patients remained hypokalaemic despite treatment with 64 mmol potassium chloride daily. 4 The relative expense, convenience and toxicity of the potassium-sparing drugs should be assessed at equivalent doses, namely spironolactone 50 mg:triamterene 200 mg:amiloride 20 mg. Potassium chloride does not correct moderate diuretic-induced hypokalaemia even at doses of 64 mmol daily.

Adult↗
PubMed1991

The effects of frusemide and triamterene on the hypokalaemic and electrocardiographic responses to inhaled terbutaline.

Fifteen normal volunteers were given 5000 micrograms inhaled terbutaline following three separate 4 day oral treatment periods with placebo, frusemide 40 mg, and frusemide 40 mg plus triamterene 50 mg. Serum potassium (K), and electrocardiographic (ECG) responses were measured after 30 min rest and 30 min after inhalation of terbutaline. Frusemide produced significant hypokalaemia compared with placebo (means and 95% CI): 3.58 mmol l-1 (3.5-3.66) vs 3.88 mmol l-1 (3.8-3.96) (P less than 0.001), and this effect was significantly attenuated by the addition of triamterene: 3.80 mmol l-1 (3.72-3.88) (P less than 0.05). Terbutaline alone also caused significant hypokalaemia: from 3.88 mmol l-1 (3.8-3.96) to 3.35 mmol l-1 (3.24-3.46) (P less than 0.001), and a lower absolute level of K was seen when combined with frusemide: 3.13 mmol l-1 (3.02-3.24) (P less than 0.05). The addition of triamterene conferred no significant protection against the combined hypokalaemia: 3.29 mmol l-1 (3.18-3.4). Changes in T wave amplitude during the study periods showed a similar pattern of response to the hypokalaemic effects. These results show that the hypokalaemic response to terbutaline was additive to that of frusemide, and that triamterene attenuated the hypokalaemic response to frusemide, but not terbutaline.

Administration, Inhalation↗
PubMed1979

Triamterene-induced immune haemolytic anaemia with acute intravascular haemolysis and acute renal failure.

Acute intravascular haemolysis and renal failure developed while a patient was taking triamterene. A direct antiglobulin test with a polyvalent reagent was positive. Serum caused agglutination of normal red cells in the presence of triamterene and caused an increase of partial haemolysis of both trypsin-treated erythrocytes and red cells from a patient with paroxysmal nocturnal haemoglobinuria (PNH) in the presence of complement. From the results of antibody-neutralization test and treatment with 2-mercaptoethanol, the presence of IgM antibody with lambda light chain could be demonstrated. The triamterene seemed to bind strongly to the red cells in vitro but in vivo there was no detectable adsorption to red cells. Haptenic inhibition was not demonstrated. From these results, it was assumed that this antibody was found to cross-react with methotrexate which has a structure similar to that of triamterene.

Acute Kidney Injury↗
PubMed1984

Chlorthalidone-triamterene: a potassium-sparing diuretic combination for the treatment of oedema.

The efficacy of a once-daily combination of chlorthalidone 50 mg plus triamterene 50 mg or chlorthalidone 100 mg plus triamterene 100 mg was compared to that of chlorthalidone 50 mg or 100 mg. This double-blind study was carried out in eighty-eight patients over a treatment period of 12 weeks. All patients entered the active medication period of 12 weeks after a placebo run-in period of 3 to 7 days, during which pretibial or malleolar pitting oedema averaging 2 to 4 mm developed. All patients started at the lower doses, i.e. forty-one started on chlorthalidone 50 mg plus triamterene 50 mg and forty-seven started on chlorthalidone 50 mg. The protocol provided for doubling the dose (but not for reducing it thereafter) at any time during the 12-week period when control of oedema was deemed inadequate. Eight of the combination therapy patients and sixteen of those on chlorthalidone required the higher doses. By Week 12, 96% of the chlorthalidone plus triamterene patients and 100% of the chlorthalidone patients had shown a reduction of at least 2 mm in depth of pits, and 92% and 72%, respectively, had complete disappearance of oedema. The decreases in pitting oedema were paralleled by mean weight losses of 2.4 kg and 3.1 kg, respectively, for the combination treatment group and the chlorthalidone group. Average serum potassium levels throughout the 12-week treatment period were 3.70 mEq/L for the patients taking the combination compared to 3.41 mEq/L of those taking chlorthalidone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗