The pharmacokinetics of glycyrrhizin (GZ) was compared in albumin-deficient rats (NAR) and normal rats (SDR) after intravenous administration. The study sought to clarify the relationship between GZ concentration and its elimination rate in serum, liver and bile when the serum protein binding of GZ decreased. Serum protein binding in SDR and NAR, respectively, was 99.7% and 68.2% for a GZ concentration of 2.5 microg/ml. At steady-state conditions after i.v. infusion of GZ (0.5-2.0 mg/h), the relationship between the GZ concentration in serum and liver was linear in the SDR but nonlinear in the NAR. For both NAR and SDR, the GZ liver level and the elimination rate was nonlinear, indicating that the elimination of GZ from liver into bile was the rate-limiting step regardless of serum protein binding, and that the liver GZ level was extremely high when serum protein binding was decreased. It is concluded that a typical dose of GZ in chronic hepatitis patients whose serum albumin level is low will not cause a decrease of therapeutic effect compared with patients with a normal serum albumin level.
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