ArticlePharmaceutical research1999
Analysis of nonlinear hepatic clearance of a cyclopentapeptide, BQ-123, with the multiple indicator dilution method using the dispersion model.
Article in Pharmaceutical research, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Article
- A compartmental model of hepatic disposition kinetics: 1. Model development and application to linear kinetics.Journal of pharmacokinetics and pharmacodynamics · 2002Article
- Quantitative evaluation of capacity-limited hepatobiliary transport based on hepatocellular diffusion model by MULTI(FEM).Journal of pharmacokinetics and pharmacodynamics · 2001Article
- A whole-body physiologically based pharmacokinetic model incorporating dispersion concepts: short and long time characteristics.Journal of pharmacokinetics and pharmacodynamics · 2001Article
- Analysis of nonlinear and nonsteady state hepatic extraction with the dispersion model using the finite difference method.Journal of pharmacokinetics and biopharmaceutics · 1998Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo bridge in vitro, in situ and in vivo kinetic analyses of the hepatic clearance of a cyclopentapeptide, BQ-123, by using dispersion models that assume nonlinear pharmacokinetics.
methodsRat livers were perfused by the multiple indicator dilution method with doses of BQ-123 ranging from 1-1000 microg. The outflow dilution curves were fitted to a two-compartment dispersion model that was solved numerically by the finite difference method. Further, in vivo plasma concentrations of BQ-123 after bolus injection were analyzed with a hybrid physiological model that incorporates the hepatic dispersion model.
resultsThe calculated Michaelis-Menten constants (Km = 12.0 microM, Vmax = 321 pmol/min/10(6) cells, P(dif) = 1.2 microl/min/10(6) cells) were comparable to those obtained previously from the in vitro isolated hepatocyte experiment (Km = 9.5 microM, Vmax = 517 pmol/min/l0(6) cells, P(dif) = 1.1 microl/min/10(6) cells). The plasma concentrations of BQ-123 at doses of 1-25 mg/kg were explained well by the hybrid physiological model.
conclusionsThese results suggest that carrier-mediated transport on the sinusoidal membrane was responsible for the in vivo hepatic elimination of BQ-123.
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