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Interaction of Etretinate with Methotrexate Pharmacokinetics in Psoriatic Patients
Author(s) -
Larsen Frederik G.,
NielsenKudsk Folmer,
Jakobsen Preben,
Schrøder Henrik,
Kragballe Knud
Publication year - 1990
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1990.tb01877.x
Subject(s) - etretinate , methotrexate , pharmacokinetics , psoriasis , volume of distribution , pharmacology , drug interaction , medicine , absorption (acoustics) , oral administration , drug , distribution (mathematics) , dermatology , mathematical analysis , physics , mathematics , acoustics
Combined treatment of psoriasis with methotrexate and etretinate may be associated with hepatoxicity. This study investigated the potential effects of steady state etretinate administration on methotrexate pharmacokinetics in six psoriatic patients. When compared with a matched group a significantly higher mean value for the maximum plasma concentration C max (992 nmol/L ± 94 SE vs 721 nmol/L ± 35 SE) for methotrexate was found ( P < .05) after intramuscular administration of 0.2 mg/kg body weight of the drug. In accordance with this finding mean values of the time (t max ) to reach C max , half‐life of the absorption (t 1/2ka ) and the apparent volume of distribution at steady state V ss were also lower than in the control groups but did not deviate significantly. Total clearance differed very little and insignificantly between the two groups. Absorption and disposition rates of etretinate during combined treatment with methotrexate were not significantly altered compared with previous results in psoriatic patients only receiving etretinate. Overall, these results indicate that the apparently increased risk for developing hepatotoxic reactions during coadministration of methotrexate and etretinate cannot be explained by drug accumulation due to pharmacokinetic interaction. A possible influence on potential hepatotoxicity of an increase of C max for methotrexate cannot be excluded.