{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T19:24:50Z","timestamp":1775157890936,"version":"3.50.1"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"4","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1988,4,1]]},"abstract":"1. The clearance and biotransformation of caffeine (1,3,7-trimethylxanthine) were investigated in eight healthy control subjects and 16 patients with cirrhosis, by measuring serial serum caffeine concentrations and recoveries of methylxanthine metabolites in urine for 48 h after a 400 mg oral caffeine load.<\/jats:p>\n 2. In the control group, the mean (\u00b1 sd) serum caffeine clearance was 1.3 \u00b1 0.4 ml min\u22121 kg\u22121 and a mean of 56.4 \u00b1 16.5% of the administered caffeine was recovered from the urine over 48 h as methyluric acids and methylxanthines. The majority of the metabolites were excreted in the first 24 h period and only 2.0 \u00b1 1.4% of the administered caffeine was excreted unchanged.<\/jats:p>\n 3. Patients with compensated cirrhosis (n = 10) metabolized caffeine similarly to the control subjects. Thus the mean serum caffeine clearance was 1.4 \u00b1 1.2 ml min\u22121 kg\u22121 and a mean of 57.2 \u00b1 11.7% of the administered caffeine was recovered from the urine over 48 h. The majority of the metabolites were excreted in the first 24 h; the pattern of metabolic excretion was unaltered and only 2.2 \u00b1 0.9% of the administered caffeine was excreted unchanged.<\/jats:p>\n 4. In the patients with decompensated cirrhosis (n = 6), significant changes were observed in caffeine metabolism. The mean serum caffeine clearance (0.4 \u00b1 0.2 ml min\u22121 kg\u22121) was significantly impaired compared with controls (P &lt; 0.01) and a significant delay was observed in metabolite excretion in the urine. Thus the mean recovery of metabolites in the urine during the first 24 h (25.0 \u00b1 11.2%) was significantly reduced compared with controls (44.1 \u00b1 12.4%, P = 0.03), whereas the mean urinary metabolite recovery in the second 24 h (20.9 \u00b1 10.5%) was insignificantly increased compared with controls (12.3 \u00b1 7.8%). Overall, the mean recovery of metabolites in the urine in 48 h (45.9 \u00b1 15.4%) was similar to that in the control group. The overall recovery of unchanged caffeine was significantly greater than in controls (5.0 \u00b1 2.8% vs 2.0 \u00b1 1.4%, P = 0.04), but the pattern of metabolite excretion was otherwise unchanged.<\/jats:p>\n 5. In the patients with liver disease there were significant linear correlations between the degree of hepatocellular dysfunction and the serum caffeine elimination half-life (r = 0.774; P &lt; 0.01) and the total recovery of methylxanthine metabolites in the urine, in the 0\u201324 h (r = 0.702; P = 0.002) and 0\u201348 h (r = 0.581; P = 0.018) periods.<\/jats:p>\n 6. Caffeine clearance is impaired in patients with decompensated cirrhosis either because of a reduction in hepatic caffeine uptake or else because of a reduction in \u2018functioning hepatocyte mass\u2019. However, the biotransformation of caffeine is unaltered in the presence of hepatic dysfunction.<\/jats:p>","DOI":"10.1042\/cs0740377","type":"journal-article","created":{"date-parts":[[2015,8,7]],"date-time":"2015-08-07T11:18:52Z","timestamp":1438946332000},"page":"377-384","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Caffeine clearance and biotransformation in patients with chronic liver disease"],"prefix":"10.1042","volume":"74","author":[{"given":"Nigel R.","family":"Scott","sequence":"first","affiliation":[{"name":"Biochemistry Department, Bromley Hospital, Bromley, Kent, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Drago","family":"Stambuk","sequence":"additional","affiliation":[{"name":"Academic Department of Medicine, The Royal Free Hospital, London"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Academic Department of Medicine, The Royal Free Hospital, London"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Marks","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Surrey, Guildford, Surrey, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marsha Y.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Academic Department of Medicine, The Royal Free Hospital, London"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/74\/4\/377\/458986\/cs0740377.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/74\/4\/377\/458986\/cs0740377.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T22:23:25Z","timestamp":1638397405000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/74\/4\/377\/74315\/Caffeine-clearance-and-biotransformation-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1988,4,1]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1988,4,1]]}},"URL":"https:\/\/doi.org\/10.1042\/cs0740377","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published":{"date-parts":[[1988,4,1]]}}}