title: CYP3A4 and CYP2A6 activities marked by the metabolism of lignocaine and coumarin in patients with liver and kidney diseases and epileptic patients.
abstract: 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)
authors.affiliation: Department of Internal Medicine, University of Oulu, Deaconess Institute of Oulu, Finland.
authors.forename: E A
authors.initials: EA
authors.lastname: Sotaniemi
authors.forename: A
authors.initials: A
authors.lastname: Rautio
authors.forename: M
authors.initials: M
authors.lastname: Bäckstrom
authors.forename: P
authors.initials: P
authors.lastname: Arvela
authors.forename: O
authors.initials: O
authors.lastname: Pelkonen
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases; D002214:Capsules; D003374:Coumarins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000652:urine; D065637:Cytochrome P-450 CYP2A6; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004827:Epilepsy / Q000201:enzymology*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007527:Isoenzymes / Q000378:metabolism; D007674:Kidney Diseases / Q000201:enzymology*; D007677:Kidney Function Tests; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D008099:Liver / Q000201:enzymology / Q000502:physiology; D008108:Liver Diseases, Alcoholic / Q000201:enzymology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D014468:Umbelliferones / Q000652:urine
chemical_list: D002214:Capsules; D003374:Coumarins; D007527:Isoenzymes; D010446:Peptide Fragments; D011347:Procollagen; D014468:Umbelliferones; C041876:procollagen Type III-N-terminal peptide; C031477:7-hydroxycoumarin; D003577:Cytochrome P-450 Enzyme System; D008012:Lidocaine; C030123:coumarin; C001173:monoethylglycinexylidide; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; C104464:CYP3A protein, human; D065637:Cytochrome P-450 CYP2A6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human