title: Pharmacokinetic properties of indinavir in rat: some limitations of noncompartmental analysis.
abstract: BACKGROUND
  Compartmental as well as noncompartmental analyses are used routinely in pharmacokinetic analysis.
  
  
  METHODS
  Pharmacokinetic parameters of the anti-HIV agent, indinavir, have been determined in six male rats applying both the compartmental and the noncompartmental analysis.
  
  
  CONCLUSIONS
  A very slow declining phase was found in the indinavir plasma concentration profile using an extended sampling time period and applying a sensitive high-performance liquid chromatography assay method. This apparent terminal elimination phase can cause some significant errors when applying noncompartmental kinetic analysis to the data, with mean residence time (MRT) (544.2 +/- 123.2 minutes), total systemic clearance (12.0 +/- 2.1 mL/min/kg), and steady-state volume of distribution (V(d) (ss)) (6.4 +/- 1.0 L/kg) being highly different from the results of compartmental kinetic analysis (MRT, Cl(total), and V(d) (ss) values of 23.7 +/- 5.9 minutes, 35.18 +/- 5.1 mL/min/kg, and 0.84 +/- 0.28 L/kg, respectively). The parameters estimated by our noncompartmental approach were also significantly different from the results of the same type of data analysis reported in the literature.
  
  
  CONCLUSIONS
  The differences in parameter estimations, while being a result of the extended plasma sampling period, which is recommended in noncompartmental analysis, support the priority of applying the compartmental analysis approach in the similar cases with some pre-assumptions, mainly ignoring the final apparent terminal elimination phase(s), very deep tissue, which involves very low drug concentrations.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran. hamidim@zums.ac.ir
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Hamidi
mesh_terms: D000818:Animals; D001825:Body Fluid Compartments / Q000502:physiology*; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D019469:Indinavir / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir