title: Coadministration of milk thistle and indinavir in healthy subjects.
abstract: OBJECTIVE
  To determine if milk thistle (silymarin) alters the pharmacokinetics of indinavir.
  
  
  METHODS
  Sequential crossover trial.
  
  
  METHODS
  General clinical research center.
  
  
  METHODS
  Ten healthy subjects.
  
  
  METHODS
  Indinavir 800 mg 3 times/day was given for four doses on days 1 and 2. Silymarin 160 mg 3 times/day was given on days 3-15. On day 16 and for one dose on day 17, both drugs were given at the same dosages.
  
  
  RESULTS
  Indinavir's pharmacokinetic parameters were evaluated at steady state both before and after administration of 14 days of silymarin. Blood samples were collected -0.25, 0.5, 1, 2, 3, 4, and 5 hours after indinavir dosing and assayed by high-performance liquid chromatography. The final pharmacokinetic model had first-order absorption after a lag time, and two compartments with first-order elimination from the central compartment. When given alone and combined with silymarin, respectively, the geometric mean (95% confidence interval [CI]) steady-state indinavir area under the plasma concentration-time curve was 20.7 hr x mg/L (15.3-28.2 hr x mg/L) and 19.4 hr x mg/L (15.8-23.6 hr x mg/L) and the trough plasma concentration was 0.340 mg/L (0.232-0.497 mg/L) and 0.232 mg/L (0.129-0.419 mg/L).
  
  
  CONCLUSIONS
  Silymarin has no apparent effect on indinavir plasma concentrations.
authors.affiliation: University of Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, New York, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: DiCenzo
authors.forename: Mark
authors.initials: M
authors.lastname: Shelton
authors.forename: Kelly
authors.initials: K
authors.lastname: Jordan
authors.forename: Christine
authors.initials: C
authors.lastname: Koval
authors.forename: Alan
authors.initials: A
authors.lastname: Forrest
authors.forename: Richard
authors.initials: R
authors.lastname: Reichman
authors.forename: Gene
authors.initials: G
authors.lastname: Morse
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D019469:Indinavir / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D020944:Silybum marianum / Q000737:chemistry; D020011:Protective Agents / Q000494:pharmacology*; D012838:Silymarin / Q000494:pharmacology*
chemical_list: D017320:HIV Protease Inhibitors; D020011:Protective Agents; D012838:Silymarin; D019469:Indinavir