LSA
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Mechanism of action
...it has been shown that the activation of particular T2R bitter taste receptors is partially involved with the bitter aftertaste sensation of saccharin and acesulfame-K. ... /This study/ addressed the question of whether /they/ could stimulate transient receptor potential vanilloid-1 (TRPV1) receptors, as these receptors are activated by a large range of structurally different chemicals. Moreover, TRPV1 receptors and/or their variants are found in taste receptor cells and in nerve terminals throughout the oral cavity. Hence, TRPV1 activation could be involved in the ... aftertaste or even contribute to the poorly understood metallic taste sensation. Using Ca(2+) imaging on TRPV1 receptors heterologously expressed in the human embryonic kidney (HEK) 293 cells and on dissociated primary sensory neurons,... /it was found/ that in both systems, .../sweeteners/ activate TRPV1 receptors, and, moreover, they sensitize these channels to acid and heat. ... /it was/also found that TRPV1 receptors were activated by CuSO(4), ZnSO(4), and FeSO(4), three salts known to produce a metallic taste sensation. In summary, .../the/ results identify a novel group of compounds that activate TRPV1 and, consequently, provide a molecular mechanism that may account for off tastes of sweeteners and metallic tasting salts.
Pharmacokinetics
Half-life
In three adult men given an intravenous bolus of 10 mg/kg bw sodium saccharin, the plasma concentration-time curve fitted a two-compartment open model with a terminal half-life of 70 min. /Sodium saccharin/
Six women with an average oral daily intake of 100-300 mg saccharin (form not specified) had maximum plasma concentrations after 0.5-1 hr and an elimination half-life of 7.5 hr.
Absorption
TRANSPLACENTAL TRANSFER OF ... (14)C-SACCHARIN ADMIN BY IV INFUSION TO RHESUS MONKEYS IN LATE PREGNANCY, WAS RAPID, BUT SLIGHT. (14)C WAS CLEARED MORE SLOWLY FROM FETAL THAN FROM MATERNAL BLOOD, & WAS DISTRIBUTED IN ALL FETAL TISSUES EXAMINED ... WAS ONLY BIOTRANSFORMED TO LIMITED EXTENT & WAS RAPIDLY EXCRETED ... .
Three groups of five men were given sodium saccharin in single oral doses of 50, 150 or 333 mg/60 kg bw. Peak plasma concentrations occurred between 30 and 60 min after dosing, and 60 and 76% was excreted unchanged in urine at 6 and 24 h, respectively. /Sodium saccharin/
IN 3 VOLUNTEERS, 85-92% OF DOSES OF 1 G 3(14)C-SACCHARIN ADMIN ORALLY FOR 21 DAYS WAS EXCRETED UNCHANGED IN THE URINE WITHIN 24 HR; NO METABOLITES WERE FOUND. WITHIN 48 HR, 92.3% OF A DOSE OF 500 MG (14)C-SACCHARIN WAS EXCRETED IN THE URINE & 5.8% IN THE FECES.
After administration of 1-g doses of soluble (sodium) saccharin [form not specified] to three men, saccharin was excreted in the urine quantitatively unchanged by two of the subjects within 48 hr. In a subsequent experiment involving six subjects, none excreted the dose quantitatively within 72 hr, but no metabolism of saccharin was detected. /Sodium saccharin/
For more Absorption, Distribution and Excretion (Complete) data for SACCHARIN (13 total), please visit the HSDB record page.
Metabolism
... 3-(14)C-SACCHARIN WAS EXCRETED UNCHANGED, MAINLY IN THE URINE (85-92% IN 24 HR) BY ADULT HUMAN SUBJECTS, BOTH BEFORE & AFTER TAKING 1 G OF SACCHARIN DAILY FOR 21 DAYS; NO METABOLITE OF SACCHARIN WAS FOUND. THESE RESULTS WERE AMPLY CONFIRMED IN ANIMAL EXPERIMENTS, IN WHICH ORALLY ADMIN (14)C-SACCHARIN WAS EXCRETED ENTIRELY UNCHANGED BY RATS ON A NORMAL DIET & BY RATS ON A DIET CONTAINING 1% & 5% OF SACCHARIN FOR UP TO 12 MO. 80-90% OF THE DOSE WAS EXCRETED IN THE URINE, 10-20% IN THE FECES; NO (14)CO2 WAS FOUND IN THE EXHALED AIR, & NO (14)CO3(2-) OR 2-SULFAMOYLBENZOIC ACID IN THE URINE.
YIELDS IN MONKEYS SULFAMOYLBENZOIC ACID & O-SULFOBENZOIC ACID. /FROM TABLE/
EXPOSURE OF MALE CHARLES RIVER CDI RATS TO 5% SACCHARIN DIET IN UTERO & THROUGHOUT WEANING, DID NOT INDUCE DETECTABLE METABOLISM. NO METABOLITES WERE DETECTED IN URINE OF NORMAL RATS GIVEN TRACER DOSE. PRETREATMENT WITH 3-METHYLCHOLANTHRENE DID NOT INDUCE SACCHARIN METABOLISM.
One female and two male volunteers excreted 85-92% of a dose of 1g (3-14)C- saccharin unchanged in the urine within 24 hr, before or after taking 1 g saccharin daily for 21 days; no metabolites were found.
Within 48 h, 92% of a dose of 500 mg [14C]saccharin taken by six male volunteers was excreted in the urine and 5.8% in the faeces. Analysis of urine and feces by highperformance liquid chromatography and thin-layer chromatography revealed only unmetabolized saccharin.
External links
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