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Vitamin E formulation affects digoxin absorption by inhibiting P‐glycoprotein (P‐GP) in humans
Author(s) -
Chan L.,
Humma L. M.,
Schriever C. A.,
Fahsingbauer L. A.,
Dominguez C. P.,
Baum C. L.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.364
Subject(s) - digoxin , pharmacokinetics , cmax , pharmacology , chemistry , pharmacodynamics , metabolite , darunavir , medicine , biochemistry , immunology , heart failure , human immunodeficiency virus (hiv) , antiretroviral therapy , viral load
Water‐soluble vitamin E(D‐α‐tocopheryl polyethylene glycol 1000 succinate (TPGS) may increase oral drug absorption. In vitro and animal data suggest that TPGS inhibits P‐gp. It is unknown whether α‐tocopherol acetate(TA), the more common formulation of vitamin E, has similar drug interaction potential. This study aimed to determine whether TPGS and TA cause comparable P‐gp inhibition in humans. Ten healthy subjects received digoxin 0.5mg POx1 to determine baseline digoxin pharmacokinetics (PK). They then received TA and TPGS (400 IU PO Q12H x15d) in random order with a 4‐week washout between treatments. Digoxin 0.5mg PO was given on days 1 and 15. Serum digoxin concentrations were measured at t=0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours; 12‐lead EKG was monitored at t=0, 3 and 6 hours after each digoxin dose. Genotyping for MDR1 (exon 26, C3435T) was determined for variant alleles. Digoxin PK were not different between 3435CC homozygous and 3435C⇒T allele carriers. Digoxin PK from each treatment were: (See Table) In summary, TPGS but not TA, altered PK without affecting pharmacodynamics of digoxin. Changes in digoxin PK with TPGS were not affected by 3435C⇒T mutation in MDR1 gene. Clinical Pharmacology & Therapeutics (2004) 75 , P95–P95; doi: 10.1016/j.clpt.2003.11.364C max [ng/mL]AUC 0–24 [ng·h/mL] 3.7±3.0p<0.05 compared with baseline; no EKG changes were observed. (Data are mean±SD).