Caffeine: A Model Compound for Measuring Liver Function

Abstract

The effects of liver disease on caffeine plasma clearance (Cl) and on exhalation of 14CO2 following i.v. injection of 2 mu Ci of [3-methyl-14C]caffeine together with 125 mg of the unlabeled compound were measured in 15 patients with cirrhosis, 11 subjects with miscellaneous liver disease, and 10 normal volunteers. Compared to mean values for Cl (2.02 +/- S.D. 0.68 ml per min per kg) and t1/2 (3.8 +/- 0.9 hr) in normal volunteers, cirrhotics were characterized by highly significant reductions in Cl (to 0.76 +/- 0.40) and prolongation in t1/2 (to 13.7 +/- 13.0), whereas the volume of distribution (VD) remained relatively unchanged (0.57 +/- 0.16 vs. 0.64 +/- 0.13 liter per kg in normals). Cumulative 14CO2 production and specific activity of 14CO2 in breath decreased in parallel (r = 0.83) with Cl. Patients with miscellaneous liver disease exhibited only small changes in Cl and t1/2; however, 14CO2 parameters in breath appeared more sensitive in indicating the slight functional derangement. In view of the correlation (Rs = 0.83) of cumulative 14CO2 excretion with the initial disappearance constant for bromosulfophthalein, the caffeine breath test may be considered as a quantitative measure of hepatic microsomal activity; based on a surprisingly close, hyperbolic relationship between Cl and fasting caffeine plasma concentrations, the latter might serve as a simple guide to severity of liver disease.

The pharmacokinetics of caffeine and its dimethylxanthine metabolites in patients with chronic liver disease.

“…It has been suggested that caffeine concentrations in the plasma after an overnight fast (Renner et al, 1984) or else plasma concentrations determined 12 h after an oral caffeine load (Wang et al, 1985) might serve as a simple guide to the severity of hepatic dysfunction. In the present study, basal serum and salivary caffeine concentrations after 72 h without caffeine were higher in our patients with liver disease than in the control subjects, but only three patients with decompensated cirrhosis had values in excess of 2 mg l-1.…”

“…Indeed it has been shown that plasma caffeine clearance is significantly reduced in patients with cirrhosis and its elimination half-life is significantly prolonged (Desmond et al, 1980;Wietholtz et al, 1981;Renner et al, 1984;Wang et al, 1985). Although caffeine loading tests are inexpensive, simple to perform and safe, the test procedure has yet to be standardised and there are few guidelines as to how the test results should be interpreted.…”

Comparative pharmacokinetics of caffeine and its primary demethylated metabolites paraxanthine, theobromine and theophylline in man.

“…For equivalent intravenous doses of the methylxanthines administered to rats, the plasma clearances and half-lives of PX and CA were similar whereas the plasma clearances of TP and TB were approximately half that for PX and the half-lives of TP and TB were approximately double that of PX. The pharmacokinetic parameters of CA, TP and TB determined in this study are similar to those generally reported in the literature (Birkett etal., 1982(Birkett etal., ,1985Blanchard & Sawers, 1983a;Bonati et al, 1982;Ogilvie, 1978;Renner et al, 1984;Tarka et al, 1983).…”

Quantitative rat liver function test by galactose single point method

“…A number of methods or drug clearance evaluations have been reported to estimate human liver function (Roberts et al 1978, Homeida et al 1979, Baker et al 1983, Renner et al 1984. The use of drugs as liver function indicators may increase the burden on liver cells, as well as a certain degree of damage.…”