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)
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Authors | E A Sotaniemi, A Rautio, M Bäckstrom, P Arvela, O Pelkonen |
Journal | British journal of clinical pharmacology
(Br J Clin Pharmacol)
Vol. 39
Issue 1
Pg. 71-6
(Jan 1995)
ISSN: 0306-5251 [Print] England |
PMID | 7756103
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Capsules
- Coumarins
- Isoenzymes
- Peptide Fragments
- Procollagen
- Umbelliferones
- procollagen Type III-N-terminal peptide
- 7-hydroxycoumarin
- Cytochrome P-450 Enzyme System
- Lidocaine
- coumarin
- monoethylglycinexylidide
- Mixed Function Oxygenases
- Aryl Hydrocarbon Hydroxylases
- CYP2A6 protein, human
- CYP3A protein, human
- Cytochrome P-450 CYP2A6
- Cytochrome P-450 CYP3A
- CYP3A4 protein, human
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Topics |
- Administration, Oral
- Adult
- Aged
- Aryl Hydrocarbon Hydroxylases
- Capsules
- Coumarins
(administration & dosage, pharmacokinetics, urine)
- Cytochrome P-450 CYP2A6
- Cytochrome P-450 CYP3A
- Cytochrome P-450 Enzyme System
(metabolism)
- Epilepsy
(enzymology)
- Female
- Humans
- Injections, Intravenous
- Isoenzymes
(metabolism)
- Kidney Diseases
(enzymology)
- Kidney Function Tests
- Lidocaine
(administration & dosage, analogs & derivatives, blood, metabolism, pharmacokinetics)
- Liver
(enzymology, physiology)
- Liver Diseases, Alcoholic
(enzymology)
- Liver Function Tests
- Male
- Middle Aged
- Mixed Function Oxygenases
(metabolism)
- Peptide Fragments
(blood)
- Procollagen
(blood)
- Umbelliferones
(urine)
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