Excretion of Phenazopyridine and its Metabolites in the Urine of Humans, Rats, Mice, and Guinea Pigs

Thomas, Barb R.; Whitehouse, L.W.; Solomonraj, G.; Paul, Catherine J.

doi:10.1002/jps.2600790410

Cited by 24 publications

(25 citation statements)

References 10 publications

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“…32 The metabolism of many azobenzenes has been analyzed by scientists interested in the effects of widely used azo-based food dyes. It varies greatly with the structure of the dye and the route of administration (e.g., whether it is exposed to gut bacteria).…”

Section: ■ Azobenzenes In Vivomentioning

confidence: 99%

Red-Shifting Azobenzene Photoswitches for in Vivo Use

et al. 2015

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Recently, there has been a great deal of interest in using the photoisomerization of azobenzene compounds to control specific biological targets in vivo. These azo compounds can be used as research tools or, in principle, could act as optically controlled drugs. Such "photopharmaceuticals" offer the prospect of targeted drug action and an unprecedented degree of temporal control. A key feature of azo compounds designed to photoswitch in vivo is the wavelength of light required to cause the photoisomerization. To pass through tissue such as the human hand, wavelengths in the red, far-red, or ideally near infrared region are required. This Account describes our attempts to produce such azo compounds. Introducing electron-donating or push/pull substituents at the para positions delocalizes the azobenzene chromophore and leads to long wavelength absorption but usually also lowers the thermal barrier to interconversion of the isomers. Fast thermal relaxation means it is difficult to produce a large steady state fraction of the cis isomer. Thus, specifically activating or inhibiting a biological process with the cis isomer would require an impractically bright light source. We have found that introducing substituents at all four ortho positions leads to azo compounds with a number of unusual properties that are useful for in vivo photoswitching. When the para substituents are amide groups, these tetra-ortho substituted azo compounds show unusually slow thermal relaxation rates and enhanced separation of n-π* transitions of cis and trans isomers compared to analogues without ortho substituents. When para positions are substituted with amino groups, ortho methoxy groups greatly stabilize the azonium form of the compounds, in which the azo group is protonated. Azonium ions absorb strongly in the red region of the spectrum and can reach into the near-IR. These azonium ions can exhibit robust cis-trans isomerization in aqueous solutions at neutral pH. By varying the nature of ortho substituents, together with the number and nature of meta and para substituents, long wavelength switching, stability to photobleaching, stability to hydrolysis, and stability to reduction by thiols can all be crafted into a photoswitch. Some of these newly developed photoswitches can be used in whole blood and show promise for effective use in vivo. It is hoped they can be combined with appropriate bioactive targets to realize the potential of photopharmacology.

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Section: ■ Azobenzenes In Vivomentioning

confidence: 99%

Red-Shifting Azobenzene Photoswitches for in Vivo Use

et al. 2015

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“…In addition, thiadiazole or triazole derivatives were documented to be effective as anti-inflammatory agents [11][12][13]. Furthermore, although limited, there are examples in the literature on the analgesic activity of azo compounds [14][15]. Recently, a series of compounds containing pyrazole, thiadiazole, and triazole rings has been synthesized in our laboratory and the compounds have been evaluated for their encouraging antibacterial [16][17][18][19] and anticonvulsant activities [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Some Novel Azo Derivatives of 3,5‐Dimethly‐1‐(2‐hydroxyethyl)pyrazole as Potent Analgesic Agents

Oruç

Koçyığıt‐Kaymakcioğlu

Oral

et al. 2006

Archiv der Pharmazie

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A series of 1-(2-hydroxyethyl)-3,5-dimethylpyrazolylazo derivatives, incorporating thiosemicarbazide 2a-c, 1,3,4-thiadiazole 3a-c, and 1,2,4-triazole-3-thione 4a-c were synthesized. The structure of these novel synthesized compounds 2a-c, 3a-c, and 4a-c was confirmed by spectral analysis. All these compounds were screened for their analgesic activity. Hot-plate and tail-immersion tests were used for the determination of the analgesic activity. Morphine, an analgesic through both spinal and supraspinal pathways, was used as a standard test drug. All compounds were administered at a dose of 100 mg/kg i.p. Among the compounds, 2-(butylamino)-5-[((1-(2-hydroxyethyl)-3,5-dimethylpyrazole-4-yl)azo)phenyl]-1,3,4-thiadiazole 3a and 4-[((1-(2-hydroxyethyl)-3,5-dimethylpyrazole-4-yl)azo)phenyl]-4-(2-phenethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 4c showed analgesic effects in both tests. Especially 4c exerted strong analgesia starting at 30 min after injection.

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“…as previously described (Thomas et al 1990). The tissue distribution of 14.C was measured by digestion of weighed tissue samples and scintillation counting (Thomas et al 1972).…”

Section: Analysesmentioning

confidence: 99%

“…we have recently published a study comparing PAP metabolism in rats, mice, guinea pigs and humans (Thomas et al 1990). This latter study measured PAP and its metabolites in urine by h.p.1.c.)…”

Section: Introductionmentioning

confidence: 96%

Metabolism and disposition of phenazopyridine in rat

Thomas¹,

Whitehouse²,

Solomonraj³

et al. 1993

Xenobiotica

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1. The blood profile, tissue distribution, biliary and urinary excretion, and metabolism of 14C-phenazopyridine (PAP) was studied in male Wistar rats. 2. Based on the blood profile of 14C the absorption of PAP from the gastrointestinal tract was rapid; the t1/2 of elimination was 7.35 h. 3. Biliary excretion was a major route of elimination with 40.7% dose excreted by this route in bile duct-cannulated rats over the 0-8 h period. The predominant metabolite was conjugated 4'-hydroxy-PAP. 4. Liver and kidney showed the highest tissue levels of PAP-derived 14C, and significant covalent binding was found in these two tissues. 5. The major urinary metabolite of PAP was 4-acetylaminophenol (NAPA) followed in order by 5,4'-dihydroxy-PAP, 5-hydroxy-PAP, 4'-hydroxy-PAP and 2'-hydroxy-PAP; unchanged PAP accounted for < 1% dose. 6. Doubling the dose of PAP to 200 mg/kg caused a proportionate decrease in urinary NAPA excretion and an increase in 5-hydroxy-PAP.

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Excretion of Phenazopyridine and its Metabolites in the Urine of Humans, Rats, Mice, and Guinea Pigs

Cited by 24 publications

References 10 publications

Red-Shifting Azobenzene Photoswitches for in Vivo Use

Red-Shifting Azobenzene Photoswitches for in Vivo Use

Synthesis of Some Novel Azo Derivatives of 3,5‐Dimethly‐1‐(2‐hydroxyethyl)pyrazole as Potent Analgesic Agents

Metabolism and disposition of phenazopyridine in rat

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