The effects of liver disease on caffeine plasma clearance (Cl) and on exhalation of 14C02 following i.v. injection of 2 pCi of [3-methyl-"C]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 C1 (2.02 f S.D. 0.68 ml per min per kg) and tl/z (3.8 f 0.9 hr) in normal volunteers, cirrhotics were characterized by highly significant reductions in C1 (to 0.76 2 0.40) and prolongation in t% (to 13.7 & 13.0), whereas the volume of distribution (VD) remained relatively unchanged (0.57 f 0.16 vs. 0.64 f 0.13 liter per kg in normals).
Cumulative 14C02 production and specific activity of 14C02 in breath decreased in parallel (r = 0.83) with C1. Patients with miscellaneous liver disease exhibited only small changes in C1 and t%; however, 14C02 parameters in breath appeared more sensitive in indicating the slight functional derangement. In view of the correlation (R, = 0.83) of cumulative l4CO, 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 C1 and fasting caffeine plasma concentrations, the latter might serve as a simple guide to severity of liver disease.