An Estimation of the Function of Hepatic Microsome (Cytochrome P4501A2) in Liver Cirrhosis using Caffeine

Yuji Yamamoto, Akio Ishikawa, Akira Osada, Katsushisa Tsuji**, Masaaki Ohtsuka, Einosuke Tanaka*, Susumu Shibuya, Takeshi Todoroki, Yashuhiro Takase, Tohru Takeshima**, Katashi Fukao

Department of Surgery, Institute of Clinical Medicine and Institute of Community Medicine*, University of Tsukuba, and Tsukuba Central Hospital**

We investigated hepatic functional reserve by using caffeine (CA), which is demethylated by centrilobularly distributed cytochrome P450lA2 in hepatic microsomes, in 32 patients with liver cirrhosis, 10 patients with cholecystolithiasis without liver cirrhosis and 5 healthy volunteers who served as controls. After an overnight fast, CA was administered orally at a dose of 2 mg/kg body weight. The serum concentration of CA decreased proportionately after oral administration of CA in volunteers. Among three primary metabolites of CA, the serum concentration of paraxanthine (PX) was higher than those of the other two metabolites, theobromine (TB) and theophylline (TP), Ninety percent of the metabolites of CA were PX. They reached maximum levels 4 to 6 hours after administration. Therefore was considered that this test should be performed 4 hours after the oral administration of CA to obtain the optimum ratio of PX/CA. The serum PX/CA ratio was significantly correlated with CA clearance (CL) in all patients (r=0.75, p<0.0001). The PX/CA ratio in patients with liver cirrhosis (0.17±0.16) was significantly lower than that in patients with cholecystolithiasis (0.44±0.13). Furthermore, a significant correlation between the serum PX/CA ratio and serum albumin, cholinesterase and IGCR15 was observed. The CA clearance test may be useful to estimate hepatic functional reserve and severity of liver disease.

Key words
caffeine, cytochrome P450, hepatic functional reserve, hepatectomy, liver cirrhosis

Reprint requests
Akio Ishikawa Department of Surgery, Institute of Clinical Medicine, University of Tsukuba
1-1-1 Tennoudai, Tsukuba, 305 JAPAN

Accepted
July 7, 1993

To read the PDF file you will need Abobe Reader installed on your computer.