title: Hepatic cytochrome P450 CYP2C activity in psoriasis: studies using proguanil as a probe compound.
abstract: Retinol and proguanil are metabolised by the same family of hepatic cytochrome P450, i.e. CYP2C. We used proguanil as a probe to study CYP2C activity, and by implication retinol metabolism, in psoriasis. In vitro studies showed that retinol competitively inhibited the hepatic metabolism of proguanil to cycloguanil. Proguanil metabolism was assessed in 82 patients with chronic plaque psoriasis. Following proguanil orally (200 mg), urine was analysed for proguanil and cycloguanil. A proguanil to cycloguanil ratio < 1 signified extensive metabolism and a ratio > 10 poor metabolism. A wider range of ratios was observed in psoriasis than previously reported for normal subjects. The proguanil to cycloguanil ratio was assessed in 10 cases each of know severe and mild psoriasis. Low CYP2C activity was associated with severe psoriasis, poor metaboliser status occurring in 50% of the severe group, but in none of the mild cases, p < 0.01. These findings may indicate differences in retinoid metabolism in psoriasis.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Liverpool, U.K.
authors.forename: N A
authors.initials: NA
authors.lastname: Helsby
authors.forename: S A
authors.initials: SA
authors.lastname: Ward
authors.forename: R A
authors.initials: RA
authors.lastname: Parslew
authors.forename: P S
authors.initials: PS
authors.lastname: Friedmann
authors.forename: L E
authors.initials: LE
authors.lastname: Rhodes
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D001189:Aryl Hydrocarbon Hydroxylases; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D005493:Folic Acid Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010641:Phenotype; D002727:Proguanil / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D011446:Prospective Studies; D011565:Psoriasis / Q000201:enzymology*; D012720:Severity of Illness Index; D014227:Triazines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D014801:Vitamin A / Q000378:metabolism
chemical_list: D000962:Antimalarials; D005493:Folic Acid Antagonists; D014227:Triazines; D014801:Vitamin A; C026009:cycloguanil; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D002727:Proguanil