title: Effect of L-phenylalanine supplementation and a high-protein diet on pharmacokinetics of cefdinir in healthy volunteers: an exploratory study.
abstract: BACKGROUND
  Upregulation of oligopeptide transport activity by dietary protein, certain dipeptides and amino acids has been reported in the rat intestine and a human intestinal cell line.
  
  
  OBJECTIVE
  In this study, the pharmacokinetics of cefdinir were investigated after L-phenylalanine supplementation and a high-protein diet (HPD) in humans to explore changes in the activities of intestinal and renal oligopeptide transporters.
  
  
  METHODS
  A normal-protein diet (NPD, 73.2 +/- 2.6 g/day), NPD + l-phenylalanine (7.5 g/day), or HPD (141.3 +/- 3.7 g/day) was given to six male healthy volunteers for 12 days followed by a single dose of cefdinir after an overnight fast in a randomized three-way crossover study with a 22-day washout. Blood and urine were collected over a 12-h period after administration of cefdinir. Concentrations of cefdinir in plasma and/or urine were measured by high-performance liquid chromatography.
  
  
  RESULTS
  Plasma concentrations and urinary excretion of the drug did not change throughout the study. Physiological variables and laboratory values did not reveal any differences between the three periods except for serum and urinary nitrogen levels and serum triglyceride.
  
  
  CONCLUSIONS
  A reason for the unchanged pharmacokinetics of cefdinir may be due to lower doses of L-phenylalanine and protein in humans than in animals when converting animal effective doses to humans.
  
  
  CONCLUSIONS
  In humans, L-phenylalanine supplementation and HPD do not seem to upregulate intestinal and renal oligopeptide transport in the ranges of duration and dose examined.
authors.affiliation: Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. tomoe@kitasato-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Fujita
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: A
authors.initials: A
authors.lastname: Yamazaki
authors.forename: M
authors.initials: M
authors.lastname: Ozaki
authors.forename: K
authors.initials: K
authors.lastname: Sahashi
authors.forename: K
authors.initials: K
authors.lastname: Shichijo
authors.forename: K
authors.initials: K
authors.lastname: Nomura
authors.forename: M
authors.initials: M
authors.lastname: Maeda
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Fujita
authors.forename: S
authors.initials: S
authors.lastname: Yokota
authors.forename: S
authors.initials: S
authors.lastname: Kuroyama
authors.forename: Y
authors.initials: Y
authors.lastname: Kumagai
authors.forename: M
authors.initials: M
authors.lastname: Majima
authors.forename: Y
authors.initials: Y
authors.lastname: Ohtani
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D019540:Area Under Curve; D001806:Blood Urea Nitrogen; D000077525:Cefdinir; D002511:Cephalosporins / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D018592:Cross-Over Studies; D004044:Dietary Proteins / Q000008:administration & dosage*; D019587:Dietary Supplements; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007677:Kidney Function Tests; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D018673:Nutrition Policy; D010649:Phenylalanine / Q000008:administration & dosage*; D010865:Pilot Projects; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D004044:Dietary Proteins; D014280:Triglycerides; D010649:Phenylalanine; D000077525:Cefdinir; D000410:Alanine Transaminase