Peringatan Keamanan

Tocopherols are considered as non-toxic but if very high doses are administered, there are reports of hemorrhagic activity. Reproductive and developmental toxicity tests are negative. These negative results were also observed in the analysis of mutagenicity and carcinogenicity.A32461

Tocopherol

DB11251

small molecule approved investigational

Deskripsi

Tocopherol exists in four different forms designated as ?, ?, ?, and ?. They present strong antioxidant activities, and it is determined as the major form of vitamin E. Tocopherol, as a group, is composed of soluble phenolic compounds that consist of a chromanol ring and a 16-carbon phytyl chain. The classification of the tocopherol molecules is designated depending on the number and position of the methyl substituent in the chromanol ring. The different types of tocopherol can be presented trimethylated, dimethylated or methylated in the positions 5-, 7- and 8-. When the carbons at position 5- and 7- are not methylated, they can function as electrophilic centers that can trap reactive oxygen and nitrogen species. Tocopherols can be found in the diet as part of vegetable oil such as corn, soybean, sesame, and cottonseed.A32436 It is currently under the list of substances generally recognized as safe (GRAS) in the FDA for the use of human consumption.L2114

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The elimination half-life ranged from 2.44 to 3.02 hours for ?-tocopherol, ?-tocopherol, and ?-tocopherol.[A32447]
Volume Distribusi The apparent volume of distribution was 0.284 ± 0.021 mL for ?-tocopherol, 0.799 ± 0.047 mL for ?-tocopherol, and 0.556 ± 0.046 mL for ?-tocopherol.[A32447]
Klirens (Clearance) Clearance ranged from 0.081 to 0.190 L/h for ?-tocopherol, ?-tocopherol, and ?-tocopherol.[A32447]

Absorpsi

The absorption of tocopherol in the digestive tract requires the presence of fat.L2120 The bioavailability of tocopherols is highly dependent on the type of isomer that is administered where the alpha-tocopherol can present a bioavailability of 36%. This isomer specificity also determines the intestinal permeability in which the gamma-tocopherol presents a very low permeability. After oral administration, the Cmax was 1353.79 ng/ml for ?-tocopherol, 547.45 ng/ml for ?-tocopherol, 704.16 ng/ml for ?-tocopherol, and 2754.36 ng/ml for ?-tocopherol. The Tmax is three to four hours for ?-tocopherol, ?-tocopherol, and ?-tocopherol and about six hours for ?-tocopherol.A32447

Metabolisme

Excess tocopherol is converted into their corresponding carboxyethylhydroxychroman (CEHC), based on the isomer of tocopherol.A32448 More deeply, the metabolism of tocopherol begins with the hepatic metabolism which is led by a CYP4F2/CYP3A4-dependent ?-hydroxylation of the side chains which leads to the formation of 13'-carboxychromanol. The metabolic pathway is followed by five cycles of ?-oxidation. The ?-oxidation cycles function by shortening the side chains, the first cycle results in the formation of carboxydimethyldecylhydroxychromanol followed by carboxymethyloctylhydroxychromanol. These two metabolites are categorized as long-chain metabolites and they are not excreted in the urine. Some intermediate-chain metabolites that are products of two rounds of ?-oxidation are carboxymethylhexylhydroxychromanol and carboxymethylbutylhydroxychromanol. These intermediate-chain metabolites can be found in human feces and urine. The catabolic end-product of tocopherols, as stated before, is CEHC which can be largely found in urine and feces.A32451 Two new metabolites have been detected in human and mice feces. These new metabolites are 12'-hydroxychromanol and 11'-hydroxychromanol. Because of their chemistry, it is thought that these metabolites can be the evidence for a ?-1 and ?-2 hydroxylation which leads to an impaired oxidation of 12'-OH followed side-chain truncation.A32451

Rute Eliminasi

The pharmacokinetic profile of tocopherol indicates a longer time of excretion for tocopherols when compared to tocotrienols.A32447 The different conjugated metabolites are excreted in the urine or feces depending on the length of their side-chain.A32448 Due to their polarity, intermediate-chain metabolites and short-chain metabolites are excreted via urine as glucoside conjugates. A mixture of all the metabolites and precursors can be found in feces. The long-chain metabolites correspond to >60% of the total metabolites in feces. It is estimated that the fecal excretion accounts for even 80% of the administered dose.A32451

Interaksi Obat

803 Data
Orlistat Orlistat can cause a decrease in the absorption of Tocopherol resulting in a reduced serum concentration and potentially a decrease in efficacy.
Pitolisant The serum concentration of Tocopherol can be decreased when it is combined with Pitolisant.
Cefotiam Cefotiam may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Mesalazine Mesalazine may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefmenoxime Cefmenoxime may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefmetazole Cefmetazole may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Pamidronic acid Pamidronic acid may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Tenofovir disoproxil Tenofovir disoproxil may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Indomethacin Indomethacin may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cidofovir Cidofovir may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefpiramide Cefpiramide may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Ceftazidime Ceftazidime may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Loracarbef Loracarbef may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefalotin Cefalotin may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Nabumetone Nabumetone may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Ketorolac Ketorolac may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Tenoxicam Tenoxicam may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Celecoxib Celecoxib may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefotaxime Cefotaxime may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Tolmetin Tolmetin may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Foscarnet Foscarnet may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Rofecoxib Rofecoxib may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Piroxicam Piroxicam may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Methotrexate Methotrexate may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cephalexin Cephalexin may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Fenoprofen Fenoprofen may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Valaciclovir Valaciclovir may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Valdecoxib Valdecoxib may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Diclofenac Diclofenac may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Sulindac Sulindac may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Bacitracin Bacitracin may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Amphotericin B Amphotericin B may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cephaloglycin Cephaloglycin may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Flurbiprofen Flurbiprofen may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Pentamidine Pentamidine may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Etodolac Etodolac may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Mefenamic acid Mefenamic acid may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Acyclovir Acyclovir may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Naproxen Naproxen may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Sulfasalazine Sulfasalazine may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Phenylbutazone Phenylbutazone may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Meloxicam Meloxicam may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Carprofen Carprofen may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefaclor Cefaclor may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Diflunisal Diflunisal may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Ceforanide Ceforanide may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Salicylic acid Salicylic acid may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Meclofenamic acid Meclofenamic acid may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Carboplatin Carboplatin may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Oxaprozin Oxaprozin may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Ketoprofen Ketoprofen may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Balsalazide Balsalazide may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Ibuprofen Ibuprofen may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefditoren Cefditoren may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Colistimethate Colistimethate may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefuroxime Cefuroxime may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefapirin Cefapirin may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefadroxil Cefadroxil may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefprozil Cefprozil may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Ceftriaxone Ceftriaxone may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Olsalazine Olsalazine may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Lumiracoxib Lumiracoxib may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefamandole Cefamandole may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefazolin Cefazolin may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefonicid Cefonicid may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefoperazone Cefoperazone may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefotetan Cefotetan may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefoxitin Cefoxitin may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Ceftizoxime Ceftizoxime may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefradine Cefradine may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Magnesium salicylate Magnesium salicylate may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Salsalate Salsalate may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Choline magnesium trisalicylate Choline magnesium trisalicylate may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefepime Cefepime may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefacetrile Cefacetrile may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Ceftibuten Ceftibuten may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cefpodoxime Cefpodoxime may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Antrafenine Antrafenine may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Aminophenazone Aminophenazone may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Antipyrine Antipyrine may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Tiaprofenic acid Tiaprofenic acid may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Etoricoxib Etoricoxib may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Hydrolyzed Cephalothin Hydrolyzed Cephalothin may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cephalothin Group Cephalothin Group may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Oxyphenbutazone Oxyphenbutazone may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Latamoxef Latamoxef may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Nimesulide Nimesulide may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Benoxaprofen Benoxaprofen may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Metamizole Metamizole may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Zomepirac Zomepirac may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Ceftobiprole Ceftobiprole may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Cimicoxib Cimicoxib may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Ceftaroline fosamil Ceftaroline fosamil may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Lornoxicam Lornoxicam may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Aceclofenac Aceclofenac may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Zaltoprofen Zaltoprofen may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Azapropazone Azapropazone may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Parecoxib Parecoxib may decrease the excretion rate of Tocopherol which could result in a higher serum level.

Target Protein

Free radicals

Referensi & Sumber

Artikel (PubMed)
  • PMID: 26751721
    Das Gupta S, Suh N: Tocopherols in cancer: An update. Mol Nutr Food Res. 2016 Jun;60(6):1354-63. doi: 10.1002/mnfr.201500847. Epub 2016 Feb 2.
  • PMID: 26272221
    Mathur P, Ding Z, Saldeen T, Mehta JL: Tocopherols in the Prevention and Treatment of Atherosclerosis and Related Cardiovascular Disease. Clin Cardiol. 2015 Sep;38(9):570-6. doi: 10.1002/clc.22422. Epub 2015 Aug 14.
  • PMID: 24119503
    Kim HJ, Giovannucci E, Rosner B, Willett WC, Cho E: Longitudinal and secular trends in dietary supplement use: Nurses' Health Study and Health Professionals Follow-Up Study, 1986-2006. J Acad Nutr Diet. 2014 Mar;114(3):436-43. doi: 10.1016/j.jand.2013.07.039. Epub 2013 Oct 9.
  • PMID: 23582353
    Chew EY, Clemons TE, Agron E, Sperduto RD, Sangiovanni JP, Kurinij N, Davis MD: Long-term effects of vitamins C and E, beta-carotene, and zinc on age-related macular degeneration: AREDS report no. 35. Ophthalmology. 2013 Aug;120(8):1604-11.e4. doi: 10.1016/j.ophtha.2013.01.021. Epub 2013 Apr 10.
  • PMID: 17561088
    Traber MG, Atkinson J: Vitamin E, antioxidant and nothing more. Free Radic Biol Med. 2007 Jul 1;43(1):4-15. doi: 10.1016/j.freeradbiomed.2007.03.024. Epub 2007 Mar 31.
  • PMID: 27493840
    Qureshi AA, Khan DA, Silswal N, Saleem S, Qureshi N: Evaluation of Pharmacokinetics, and Bioavailability of Higher Doses of Tocotrienols in Healthy Fed Humans. J Clin Exp Cardiolog. 2016 Apr;7(4). doi: 10.4172/2155-9880.1000434. Epub 2016 Apr 28.
  • PMID: 10385606
    Brigelius-Flohe R, Traber MG: Vitamin E: function and metabolism. FASEB J. 1999 Jul;13(10):1145-55.
  • PMID: 26981194
    Schmolz L, Birringer M, Lorkowski S, Wallert M: Complexity of vitamin E metabolism. World J Biol Chem. 2016 Feb 26;7(1):14-43. doi: 10.4331/wjbc.v7.i1.14.
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