title: Pharmacokinetics of the transdermal delivery of benfotiamine.
abstract: OBJECTIVE
  Accumulation of advanced glycation endpoints is a trigger to the development of diabetic peripheral neuropathy, which is a common complication of diabetes. Oral administration of benfotiamine (BFT) has shown some preclinical and clinical promise as a treatment for diabetic peripheral neuropathy. The purpose of this study was to evaluate the method of transdermal delivery of BFT as a possible, viable route of administration for the treatment of diabetic peripheral neuropathy.
  
  
  METHODS
  A single application of 10 mg of BFT was given to guinea pigs topically. The levels of thiamine (T), thiamine monophosphate, thiamine diphosphate, S-benzoylthiamine and BFT were measured in the blood, skin and muscle at different time points within 24 h.
  
  
  RESULTS
  At the 24-h time point, following the single BFT dose, the T level was increased 10× in the blood, more than 7× in the skin and almost 4× in the muscle compared to the untreated animals. The total T content (total) was increased 7× in the blood, 17× in the skin and 3× in the muscle compared to the untreated animals.
  
  
  CONCLUSIONS
  This strong increase in the tissue levels of T and the associated metabolic derivatives levels found in the blood and local tissues following a single dose indicate that topically applied BFT may be a viable and advantageous delivery method for the treatment of diabetic peripheral neuropathy.
authors.affiliation: BioChemics Inc., 99 Rosewood Drive, Suite 270, Danvers, MA, 01923-4537, USA. pzhu@biochemics.com.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: BioChemics Inc., 99 Rosewood Drive, Suite 270, Danvers, MA, 01923-4537, USA.
authors.forename: Gyula
authors.initials: G
authors.lastname: Varadi
authors.affiliation: Intrepid Life Sciences, Andover, MA, 01810, USA.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Carter
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000378:metabolism; D016503:Drug Delivery Systems; D006168:Guinea Pigs; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D013831:Thiamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D013831:Thiamine; C013835:benphothiamine
keywords: Advanced glycation endproducts; Benfotiamine; Blood; Diabetic neuropathy; Muscle; Skin; Thiamine; Transdermal delivery