title: The effects of food on the pharmacokinetics of mitiglinide tablets in healthy volunteers and a novel mass-spectrometric (UPLC-MS/MS) method for such studies.
abstract: OBJECTIVE
  Mitiglinide (MGN) is a new insulinotropic agent of the glinide class with rapid onset. The effects of food intake on the pharmacokinetic (PK) profile of mitiglinide tablets after single oral administration have not yet been reported in healthy adults. We aimed to assess the effects of food intake on the PK properties of mitiglinide (MGN) tablets, using a novel analytical method, after single escalating oral doses in healthy Chinese volunteers.
  
  
  METHODS
  In this open-label, randomized, single-dose (three distinct doses), two-way crossover PK study, three doses of MGN 5, 10 or 20 mg were administered to healthy adult volunteers after an overnight fast (fasted condition) or low-fat breakfast (fed condition) (period 1). After 7 days, the participants received the same dose under the opposite fed/fasted condition (period 2). Serial blood samples were obtained before and through 8 h after study drug administration. Concentrations of MGN in plasma were determined using UPLC-MS/MS. Adverse events (AEs) were monitored and recorded on each in-clinic day.
  
  
  CONCLUSIONS
  Twenty-four Chinese volunteers (eight [four men, four women] volunteers per group) were enrolled in the study. The extent of absorption of MGN was similar in both fed and fasted conditions at single doses in the range 5-20 mg. Food intake was associated with decreases in C(max) by 60·4% to 65·2% in the three dose groups and greatly delayed T(max) [0·36(Standard deviation 0·16) vs. 1·75(0·92) hours with 5 mg, 0·29(0·19) vs. 1·97(0·81) hours with 10 mg and 0·30(0·10) vs. 1·18(0·68) hours with 20 mg; all, P < 0·05]. t(1/2) , CL/F and V/F (P > 0·05) were unaffected. MRT(0-8) at the 5 and 10-mg doses, but not at the 20-mg dose, were markedly lower in fasted volunteers than fed volunteers (P < 0·05).
  
  
  CONCLUSIONS
  Using a novel UPLC-MS/MS method, we showed that food intake affected the rate but not the extent of absorption of MGN within the 5- to 20-mg dose range. Gender did not appear to affect the PK properties of MGN in either fasted or fed states. MGN should be preferably taken before food.
authors.affiliation: Clinical Pharmacy Research Institute, The Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: L-J
authors.initials: LJ
authors.lastname: Cai
authors.forename: W-X
authors.initials: WX
authors.lastname: Peng
authors.forename: R-H
authors.initials: RH
authors.lastname: Zhu
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: Q-Z
authors.initials: QZ
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000328:Adult; D044466:Asian People; D002681:China; D002853:Chromatography, Liquid / Q000379:methods*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D054833:Isoindoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D013607:Tablets; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D054833:Isoindoles; D013607:Tablets; C087255:mitiglinide