Variations in the fate of triamterene

Pruitt, Albert W.; Winkel, Joan S.; Dayton, Peter G.

doi:10.1002/cpt1977215610

Cited by 55 publications

(19 citation statements)

References 11 publications

(17 reference statements)

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“…The renal excretion of furosemide, however, was substantially diminished (36% for furosemide-retard and 25% for furosemide-retard/triamterene), In contrast to this 14.8% of the dose as triamterene and 62% of the dose as OH-TA sulfate were excreted within 12 h. These values are substantially higher than those found after the administration of triamterene alone (2,9,26). In our studies the relation of OH-TA sulfate to triamterene in the plasma was higher than that in urine; this was in agreement with the results obtained by Gundert-Remy et al We have, as yet, no explanation for the high renal excretion of OH-TA sulfate and triamterene or for the diminished excretion of furosemide after administration of a combination of the two substances.…”

Section: Pharmacokinetic Of Triamterenecontrasting

confidence: 47%

Bioavailability and elimination kinetics of the combination furosemide-retard/triamterene

Schuster¹,

Loew²,

Knoell³

1985

European Journal of Drug Metabolism and Pharmacokinetics

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In a pharmacokinetic study on 18 healthy male volunteers the bioavailability and elimination kinetics of furosemide-retard and the combination furosemide-retard/triamterene were investigated and compared with the non-retarded form and another retard form of furosemide. The relative bioavailability of the non-retarded form of furosemide was distinctly reduced by the retardation in the substances investigated. It varied between 42-66% in the plasma and between 37-73% in the urine. In the combination with triamterene the serum concentration time curve of furosemide was only slightly modified but the renal excretion of furosemide was more influenced (36% for furosemide-retard and 25% for furosemide-retard/triamterene). In comparison, the values for the renal excretion of triamterene and OH-TA sulfate were distinctly greater than those obtained after administration of triamterene alone. A renewed increase of the plasma concentration and renal excretion of furosemide were observed between 9 and 10.5 h after administration of furosemide-retard/triamterene. This observation suggests that a further absorption of furosemide occurs as a consequence of the delayed release from distal parts of the small intestine or from the large intestine.

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Section: Pharmacokinetic Of Triamterenecontrasting

confidence: 47%

Bioavailability and elimination kinetics of the combination furosemide-retard/triamterene

Schuster¹,

Loew²,

Knoell³

1985

European Journal of Drug Metabolism and Pharmacokinetics

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“…CB [7] was dissolved in distilled water, and the solution was evaporated slowly at room temperature to get colorless block-shaped crystals of CB [7]. Elemental analysis for C 42 The powder of CB [7] for the synthesis of the drug−CB [7] complexes was obtained by drying the crystals of CB [7]-(H 2 O) 22 at 100°C under vacuum for 24 h to get CB [7](H 2 O) 13 . Elemental analysis for C 42 [7] + H] + ).…”

Section: ■ Introductionmentioning

confidence: 99%

“…Cucurbit [7]uril was synthesized by the reported methods, 27,32,50 which was further purified by recrystallization from distilled water, and characterized by single X-ray analysis, 1 H NMR spectra were recorded on a Varian Mercury 300 MHz spectrometer. 13 C NMR spectra were recorded on Bruker UltraShield 400 MHz spectrometer.…”

Section: ■ Introductionmentioning

confidence: 99%

The Delivery of Triamterene by Cucurbit[7]uril: Synthesis, Structures and Pharmacokinetics Study

Chen

Jiang

et al. 2013

Mol. Pharmaceutics

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In recent years, cucurbit [7]uril (CB [7]) has attracted great attention in drug delivery. Though the effect of CB [7] in enhancing the solubility of water insoluble drugs has been validated, the underlying mechanism remains poorly understood, particularly at a molecular level. This study is designed to evaluate a CB [7]-based pharmaceutical formulation to improve solubility and bioavailability of triamterene (a mild potassium-sparing diuretic). Two polymorphs of triamterene@CB [7] were obtained, and their crystal structures were determined by single crystal X-ray diffraction. The CB [7] molecule forms a stable host−guest complex with triamterene (K a = 1.69 ± 0.34 × 10 4 M −1 ) in aqueous solution (pH = 1.0). The results of dissolution study demonstrate that the apparent solubility value of triamterene@CB [7] complex in 0.1 M HCl is 1.6 times as large as that of triamterene, while free triamterene was released from triamterene@CB [7] complex in phosphate buffer of pH 6.8. Pharmacokinetic studies in rats reveal that the AUC 0−∞ value of triamterene@CB [7] complex increases 2.8-fold compared with that of free triamterene, and t 1/2 is prolonged from 1.42 to 2.61 h (P < 0.05) after oral administration. The increased solubility and oral bioavailability are attributed to the formation of a hydrophilic capsule composed of two CB [7] molecules, in which two insoluble triamterene molecules are encapsulated. These results demonstrate that triamterene@CB [7] complex is a stable and effective pharmaceutical formulation. KEYWORDS: cucurbit [7]uril, triamterene, crystal structure, solubility, pharmacokinetics ■ INTRODUCTIONPoor aqueous solubility is a major bottleneck in drug discovery and drug development: more than 40% of drug candidates are poorly water-soluble, and poor aqueous solubility is the main factor to restrict the bioavailability of drugs.1,2 Various approaches have been investigated to improve solubility of drugs, including cocrystal, 3,4 salts, 5 prodrugs, 6 solid dispersion, 7 macrocyclic hosts (e.g., cyclodextrins, cucurbiturils), 8,9 etc. Triamterene, 2,4,7-triamino-6-phenylpteridine (Scheme 1) is a mild potassium-sparing diuretic used either alone or in combination with potassium-wasting diuretics such as hydrochlorothiazide.10,11 It displays low oral bioavailability, and there exists wide intersubject variation because of its poor aqueous solubility (45 mg/L). 12,13 Though triamterene contains three primary amine groups, various methods to obtain soluble salts failed, probably due to its weak basicity. 12 To date, only a few formulations have been proposed to improve the solubility of triamterene, including cyclodextrins 14,15 and solid dispersions. 16,17 However, parenteral administration of β-cyclodextrin results in renal toxicity, 18 and solid dispersions are often physically unstable upon storage at elevated temperature and humidity, 19 and neither of the two triamterene formulations has been applied for clinical therapy. Therefore, the development of new pharmaceutical formulation of triam...

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“…Only recently have TA pharmacokinetics been thor oughly investigated [5][6][7][8][9][10][11]. These studies clearly docu mented that the bioavailability of TA was very formula tion-dependent.…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…Alterations in the pharmacokinetics of TA occur in a number of disease states including liver disease [6,8,11], renal disease [8,9] and as a consequence of aging [5,8]. The liver serves a primary role in the metabolism of TA since this drug undergoes extensive biotransformation to OH-TA and OH-TA ester [8,10], In patients with cirrho sis, the elimination half-life for TA is markedly pro longed, increasing from 3 to approximately 12 h as a consequence of diminished hydroxylation to OH-TA [8].…”

Section: Pharmacokinetics In Disease Statesmentioning

confidence: 99%

Triamterene and the Kidney

Sica¹,

Gehr²

1989

Nephron

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Triamterene (TA) is a mild ‘potassium-sparing’ diuretic usually employed in combination with other more potent diuretics in the treatment of hypertension. TA pharmacokinetics and pharmacodynamics in normal volunteers, elderly subjects and in patients with renal and hepatic dysfunction are reviewed. A variety of adverse renal effects, such as abnormalities in urinary sediment, nephrolithiasis, interstitial nephritis and acute renal failure, has been reported to occur and is also reviewed. Of particular concern with the increased availability of ‘over-the-counter’ nonsteroidal anti-inflammatory medications (NSAID) is the adverse interaction between TA and NSAID which may culminate in acute renal failure. Although a rare occurrence, the clinician should be aware of potential adverse reactions associated with the use of TA.

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Variations in the fate of triamterene

Cited by 55 publications

References 11 publications

Bioavailability and elimination kinetics of the combination furosemide-retard/triamterene

Bioavailability and elimination kinetics of the combination furosemide-retard/triamterene

The Delivery of Triamterene by Cucurbit[7]uril: Synthesis, Structures and Pharmacokinetics Study

Triamterene and the Kidney

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