1 Four cytochrome P-450 enzyme activities, 7-ethoxyresorufin O-deethylase (ERDE), coumarin 7-hydroxylase (CH), 7-ethoxycoumarin 0-deethylase (ECDE) and aryl hydrocarbon hydroxylase (AHH) were measured in human liver needle biopsy samples from smokers and non-smokers. Cigarette smoking was verified and quantitated by measuring plasma cotinine levels.3 Enzyme inhibitory monoclonal antibodies (MAb) to a 3-methylcholanthrene-induced (MAb 1-7-1) and phenobarbitone-induced (MAb 2-66-3) rat hepatic cytochrome P-450 were used to measure the contribution of MAb-defined, epitope-specific cytochromes P-450 to the total reaction measured for each of the above activities. 3 ERDE activity was significantly elevated in the livers of cigarette smokers, whereas AHH, CH or ECDE activities were not affected by cigarette smoking. No correlation was observed between plasma cotinine concentration and ERDE activity. 4 MAb 1-7-1 inhibited hepatic ERDE activity to a variable extent (from 0 to 65%), but had very little or no effect on AHH, CH or ECDE activities. The inhibitory effect of MAb 1-7-1 on ERDE activity was greater than 50% in the non-smokers. MAb 2-66-3 had no inhibitory effect on any of the enzyme activities studied. 5 In contrast to liver both ERDE and AHH on human placental microsomes from cigarette smokers were inhibited by MAb 1-7-1. The MAb 2-66-3 was without effect. 6 Cigarette smoking induces a form of P-450 in human liver, responsible for ERDE activity, that contains an epitope recognized by MAb 1-7-1. This form of cytochrome P-450 is insensitive to MAb 2-66-3 and is not contributing to AHH, CH or ECDE activities of human liver.

1. The in vitro hepatic metabolism of lignocaine to monoethylglycinexylide (MEGX) is mediated by CYP3A4 and that of coumarin to 7‐hydroxycoumarin (7OHC) by CYP2A6. We investigated the usefulness of monitoring serum MEGX concentrations (after 1 mg kg‐1 lignocaine i.v.) and urinary 7OHC excretion (after 5 mg coumarin p.o.) to reflect liver function in patients with liver (n = 36), kidney (n = 12) and epileptic (n = 12) disease and in control subjects (n = 20). The extent of liver disease was assessed using measurements of serum aminoterminal propeptide (PIIINP) and Child‐Pugh grades. 2. Serum concentrations of MEGX were decreased in severe (4.6 +/‐ 3.0 s.d. ng ml‐ 1), moderate (19.1 +/‐ 11.6 s.d. ng ml‐1) and mild (32.8 +/‐ 14.2 s.d ng ml‐1) liver disease as compared with controls (53.4 +/‐ 15.8 s.d ng ml‐1). The excretion of 7OHC over 2 h was decreased in severe (18.0 +/‐ 10.3 s.d % of dose) and moderate (34.2 +/‐ 15.6 s.d %), but not in mild (49.7 +/‐ 19.0 s.d %) liver disease as compared with that in controls (56.2 +/‐ 11.6%). 3. In epileptic patients the urinary recovery of 7OHC was increased (2 h value 69.5 +/‐ 13.2 s.d %) suggesting enzyme induction. In contrast, serum MEGX concentration were low (40.0 +/‐ 14.1 s.d ng ml‐1), possibly due to competition for CYP3A4 between lignocaine and antiepileptic drugs. 4. In patients with kidney disease serum MEGX concentration (56.5 +/‐ 26.1 s.d ng ml‐1) was similar to that in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-four patients with steatotic liver underwent computerized tomography (CT) and ultrasound (US) examinations and liver biopsy, performed within a maximum interval of 6 weeks. The CT and US findings were compared with the fat and fibrous content of the biopsy specimens. A good linear inverse correlation between the CT findings and fat content was found. The ranges of CT values were 39-60 HU (mean, 52 HU) for mild fat content (less than or equal to 9.9%), 4-46 HU (mean, 27 HU) for moderate fat content (10.0-24.9%), and -6 to 19 HU (mean, 10 HU) for severe fat content (greater than or equal to 25.0%). With US it was possible to estimate roughly the fat and fibrous content of the liver. There was always the 'bright liver' finding in patients with 10.0% or more fat content, but it was impossible to estimate the content of fat more accurately. 'Bright liver' was also found in most patients with mildly and in all patients with severely increased fibrous content. It was impossible to differentiate the latter from each other or from the 'bright liver' caused by fatty degeneration.

The effect of cimetidine on human microsomal drug metabolism was studied. In five of six healthy volunteers therapeutic doses of cimetidine prolonged the half-life of antipyrine (range 12-37%; p < 0.05). Its clearance was decreased in five subjects (range 2-18%) and was increased in one subject (15%), the changes not being statistically significant. The volume of distribution increased on average by about 14% (range 9--19%; p < 0.001). Cimetidine in vitro inhibited the hydroxylation of benzo(a)pyrene and coumarin, as well as the O-deethylation of 7-ethoxycoumarin, by homogenised liver biopsies. The in vitro studies suggest that the effect of cimetidine on antipyrine elimination is due to inhibition of microsomal drug metabolism, which may prove an important drug interaction.