title: In Vivo Hypoglycemic Studies of Polyherbal Phytoceuticals, Their Pharmacokinetic Studies and Dose Extrapolation by Allometric Scaling.
abstract: BACKGROUND
  This work reports the safety profiling, in vivo hypoglycemic and pharmacokinetic studies of three phytoceuticals viz. conventional and sustained release tablets and microspheres each containing a polyherbal product phytocomposite (PHC) as the active ingredient. PHC is prepared from the leaf extracts of Ficus benghalensis: Syzigium cumini: Ocimum sanctum mixed in the weight ratio of 1:1:2. Further no observed adverse effect level (NOAEL), maximum recommended starting dose (MRSD) in human and prediction of human pharmacokinetic parameters have been accomplished by allometric equations.
  
  
  METHODS
  Acute and sub chronic studies of the phytoceuticals were done as per OECD and in vivo hypoglycemic studies in STZ induced diabetic rats. Plasma concentrations of the active constituent rutin (pharmacologically active compound of PHC) were determined by HPLC and other pharmacokinetic parameters using PK Solver. Repeated dose toxicity was carried out to determine the NOAEL value, MRSD estimated using allometric formulas of body surface area and clearance (CL) and volume of distribution (Vd) predicted by allometric equations of single species scaling.
  
  
  RESULTS
  Phytoceuticals showed a wide range of safety profile with a significant lowering of blood gluco-lipid level. The values of the pharmacokinetic parameters for different doses of phytoceuticals showed that the active concentration was maintained in plasma level and each formulation complied with their relevant quality criteria. NOAEL value was 5000 mg/kg/body weight and MRSD was 4864.86 mg.
  
  
  CONCLUSIONS
  Phytoceuticals prepared are safe and effectively controlled blood gluco lipid level. Animal to human dose extrapolation and prediction of human pharmacokinetic parameters by allometry was convenient.
authors.affiliation: School of Medical Science and Technology, IIT Kharagpur, Kharagpur, West Bengal, 721302. India.
authors.forename: Baishakhi
authors.initials: B
authors.lastname: De
authors.affiliation: School of Medical Science and Technology, IIT Kharagpur, Kharagpur, West Bengal, 721302. India.
authors.forename: Koushik
authors.initials: K
authors.lastname: Bhandari
authors.affiliation: SSS Indira College of Pharmacy, Vishnupuri, Nanded-431606. India.
authors.forename: Prakash
authors.initials: P
authors.lastname: Katakam
authors.affiliation: School of Medical Science and Technology, IIT Kharagpur, Kharagpur, West Bengal, 721302. India.
authors.forename: Analava
authors.initials: A
authors.lastname: Mitra
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003692:Delayed-Action Preparations; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D030681:Ficus; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D008954:Models, Biological; D019055:No-Observed-Adverse-Effect Level; D031339:Ocimum; D064209:Phytochemicals / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D008517:Phytotherapy; D010936:Plant Extracts / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D018515:Plant Leaves; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012431:Rutin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D027842:Syzygium; D013607:Tablets
chemical_list: D001786:Blood Glucose; D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D064209:Phytochemicals; D010936:Plant Extracts; D013607:Tablets; D012431:Rutin
keywords: Phytoceuticals; allometry; hypoglycemic; no observed adverse effect level; pharmacokinetics; pharmacologically active dose; phytocomposite