Absorption, Distribution and Excretion
Up to 15% of therapeutic dose of phenolphthalein is absorbed and eliminated by kidney, most of it in conjugated form.
Urine becomes pink or red if it is sufficiently alkaline (pH 7or more). Some absorbed drug is also exreted in the bile, and the resulting enterohepatic cycle may contribute to prolongation of laxative effect.
Biliary excretion of metabolites of...phenolphthalein...in rats was shown...to be increased by pre-treatment with hepatic-microsomal-enzyme inducers, and to be decreased by enzyme inhibitors after dosing with parent compound, but no effect was observed after dosing with metabolites.
Phenolphthalein glucuronide (I) excreted more rapidly than phenolphthalein (II) following iv injection, suggesting that uptake of (I) from blood imposes rate limitation which outweighs the lack of conjugation before excretion.
For more Absorption, Distribution and Excretion (Complete) data for PHENOLPHTHALEIN (14 total), please visit the HSDB record page.

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Metabolism / Metabolites
Phenolphthalein that had undergone conjugation, but no unmetabolized phenolphthalein, was excreted into breast milk in concentrations up to 1.0 ug/mL after a single 200-800 mg dose in 22 lactating women. Bowel movements occurred in 16 of the women after the dose, but none of the nursing infants had diarrhea.
Yields phenolphthalein-beta-d-glucuronide in rat, in mouse. /from table/
Phenolphthalein is absorbed in the intestine and is almost completely converted to its glucuronide during extensive first-pass metabolism in the intestinal epithelium and liver via uridine diphosphate glucuronosyltransferase (UDPGT) in rodents and dogs. In guinea-pigs, small amounts of sulfate-conjugated metabolites have been detected in isolated mucosal sheets originating in the jejunum and colon. Fecal excretion is the major route of elimination of phenolphthalein in rats, while in mice both urinary and fecal elimination are important. The metabolites identified in urine and feces are phenolphthalein glucuronide, phenolphthalein sulfate and phenolphthalein hydroxide.
...The major metabolite was PHTH glucuronide. Three minor metabolites were detected. A sulfate conjugate and and a hydroxylated metabolite were identified by comparison of retention times and 1H NMR and/or mass spectra with synthetic standards. A diglucuronide conjugate was tentatively identified. Biliary elimination was extensive in rats (35% of dose within 6 hr); the only product detected in bile was phenolphthalein glucuronide

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Biological Half-Life
Classical compartmental pharmacokinetics model developed to describe systemic blood concentration-time profile of phenolphthalein following single iv bolus injection; used to simulate 24-hr time course of blood concentration. Indication that long t/2 are artifacts of recirculation.

Interactions
Pretreatment of rats with sodium methotrexate (1 mg, orally, daily for 5 days) or vincristine sulfate (0.03 mg/kg, iv, weekly for 3 wk) markedly reduced biliary excretion of phenolphthalein (10 mg/kg, iv) indicating that hepatic function was decreased.

[1]. Color indicator for supramolecular polymer chemistry: phenolphthalein-containing thermo- and pH-sensitive N-(Isopropyl)acrylamide copolymers and β-cyclodextrin complexation. Macromol Rapid Commun. 2013 Jul 12;34(13):1085-9.

Phenolphthalein can cause cancer according to The Food and Drug Administration (FDA) and The National Toxicology Program.
Phenolphthalein appears as white or yellowish-white to pale orange fine crystalline powder. Odorless. Aqueous solution is acidic. Colorless to pH 8.5; pink to deep-red above pH 9. Colorless in presence of large amounts of alkali. Tasteless. (NTP, 1992)
Phenolphthalein is a member of phenols. It is functionally related to a 2-benzofuran-1(3H)-one.
Phenolphthalein was withdrawn in Canada due to concerns with carcinogenicity in 1997.
Phenolphthalein has been reported in Caragana conferta with data available.
Phenolphthalein is an organic compound used as a laboratory reagent and pH indicator. Phenolphthalein exerts laxative effects by stimulating the intestinal mucosa and constricting smooth muscles. However, phenolphthalein is no longer used as a laxative due to the suspected carcinogenicity of this compound.
Phenolphthalein was withdrawn in Canada due to concerns with carcinogenicity in 1997.
An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic.

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Drug Indication
Used for over a century as a laxative.

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Mechanism of Action
Stimulant drugs alter fluid and electrolyte absorption, producing net intestinal fluid accumulation and laxation. Increased concentrations of cyclic 3'-5'-adenosine monophosphate (CAMP) occurring in clonic mucosal cells may alter the permeability of these cells leading to net fluid accumulation and laxative action. Phenolphthalein also acts directly or reflexly to increase the the activity of the small intestine. Phenolphthalein acts mainly on the colon about 6 hours after ingestion.
When taken orally, it is thought to be dissolved by intestinal juices and bile and to stimulate intestinal musculature, chiefly that of colon.
Phenolphthalein increased intestinal fluid volume in rat colon in situ, apparently via stimulation of prostaglandin E biosynthesis in colon.
Water absorption from intestines of 6 pt with ileostomies and from rats was measured after administration of phenolphthalein. Results indicate that some laxative effects result from inhibition of water absorption in large and small intestines.
.... A catechol metabolite of PT, hydroxyphenolphthalein (PT-CAT), was recently identified and may be the molecular species responsible for at least part of the toxicity/carcinogenicity of PT. We hypothesize that PT-CAT inhibits the enzyme catechol-O-methyltransferase (COMT) and therefore potentiates genotoxicity by either PT-CAT itself or the endogenous catechol estrogens (CEs) in susceptible tissues. The present studies were conducted to determine the effects of PT treatment and PT-CAT itself on the COMT-mediated metabolism of 4- and 2-hydroxyestradiol both in vitro and in vivo. Female mice were treated with PT (50 mg/kg/d) for 21 days and then euthanized. PT-CAT concentration in urine reached plateau levels by 7 days of exposure. An O-methylated metabolite of PT-CAT was detected in feces. In vitro experiments demonstrated that PT treatment resulted in an increase in free CEs, which are normally cleared by COMT and a concurrent decrease in the capacity of hepatic catechol clearance by COMT. In vitro, PT-CAT was a substrate of COMT, with kinetic properties within the range measured with endogenous substrates. PT-CAT was an extremely potent mixed-type inhibitor of the O-methylation of the catechol estrogens, with 90-300 nM IC50s.

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Therapeutic Uses
Cathartics; Indicators and Reagents
...Has...been widely employed as cathartic. ... /it/ is avail...in numerous proprietary preparations.
Since ... laxative effects are not usually produced in less than 6 hr after oral administration, they are often taken at bedtime, to produce their effect next morning. Because of adverse effects, use of these agents should be limited to 10 consecutive days. /diphenylmethane derivatives/
(VET): Has been used as a laxative.
Cathartic drug in laxatives; acid-base indicator

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Drug Warnings
Use of phenolphthalein by women during breast-feeding may cause diarrhea in their infants.
Patients should be warned of possible coloring of urine and feces.

C20H14O4

318.32

318.089

77-09-8

4764

White to off-white solid powder

1.4±0.1 g/cm3

557.8±50.0 °C at 760 mmHg

258-263 °C

206.5±23.6 °C

0.0±1.6 mmHg at 25°C

1.693

2.63

2

4

2

24

438

0

KJFMBFZCATUALV-UHFFFAOYSA-N

InChI=1S/C20H14O4/c21-15-9-5-13(6-10-15)20(14-7-11-16(22)12-8-14)18-4-2-1-3-17(18)19(23)24-20/h1-12,21-22H

3,3-bis(4-hydroxyphenyl)-2-benzofuran-1-one

Phthalimetten; Euchessina; Phenolphthalein

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 50 mg/mL (~157.07 mM)

Solubility in Formulation 1: 2.5 mg/mL (7.85 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (7.85 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: 2.5 mg/mL (7.85 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)