J Clin Pharmacol
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METHODS

Serum Metabolite/Caffeine Ratios as a Test for Liver Function

Jadwiga Jodynis-Liebert, PhD, Jan Flieger, MD, Arleta Matuszewska, MS and Jacek Juszczyk, MD, PhD

Department of Toxicology (Dr. Jodynis-Liebert, A. Matuszewska) and the Department of Infectious Diseases (Dr. Flieger, J. Juszczyk), University of Medical Sciences, Pozna[S1], Poland.

The aim of this study was to test the usefulness of the metabolite/caffeine ratio for the evaluation of hepatic dysfunction. Subjects with liver cirrhosis and chronic hepatitis, as well as healthy volunteers, were given the oral dose of 300 mg caffeine. Blood samples were collected after 4, 8, and 12 hours. Concentrations of caffeine (CA) and its three metabolites—paraxanthine (PX), theobromine (TB), and theophylline (TP)—were determined by high-performance liquid chromatography. Pharmacokinetic parameters of caffeine and PX/CA, TB/CA, and TP/CA ratios were calculated. Elimination of caffeine was decreased in cirrhotics in comparison with healthy volunteers, as proved by the values of clearance (0.035 vs. 0.094 L/h/kg), elimination coefficient (0.061 vs. 0.153 h-1), and half-life (11.4 vs. 4.3 h). Serum metabolite/caffeine ratios were significantly reduced in cirrhotic patients: PX/CA by more than 80%, TB/CA by 50% to 70%, and TP/CA by 40% to 70%. The reduction of the ratios in chronic hepatitis patients was lower and did not occur at all time points. A high correlation was found between caffeine clearance and metabolite/caffeine ratios. Metabolite/caffeine ratios calculated in a single blood sample collected 8 or 12 hours after caffeine administration could provide a practical assessment of hepatic function in cirrhotic patients. The value of the test for the chronic hepatitis patients is limited.

Key Words: Caffeine pharmacokinetics • metabolite/caffeine ratios • liver diseases

Address for reprints: J. Jodynis-Liebert, University of Medical Sciences, Department of Toxicology, Dojazd 30, 60-631 Pozna[S1], Poland.


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