| Title | Pharmacokinetic properties of indinavir in rat: some limitations of noncompartmental analysis. | | Author(s) | Hamidi M | | Institution | Department of Pharmaceutics, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran. | | Source | Drug Dev Ind Pharm 2009 Sep 1. | | Abstract | Background: Compartmental as well as noncompartmental analyses are used routinely in pharmacokinetic analysis. Materials and methods: Pharmacokinetic parameters of the anti-HIV agent, indinavir, have been determined in six male rats applying both the compartmental and the noncompartmental analysis. Results and discussion: 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.
Conclusion: 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19722914 |
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