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Interferon‐β treatment in patients with multiple sclerosis does not alter CYP2C19 or CYP2D6 activity
Author(s) -
Hellman Karin,
Roos Ewa,
Österlund Anna,
Wahlberg Anneli,
Gustafsson Lars L.,
Bertilsson Leif,
Fredrikson Sten
Publication year - 2003
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.0306-5251.2003.01859.x
Subject(s) - mephenytoin , debrisoquine , cyp2c19 , cyp2d6 , medicine , multiple sclerosis , pharmacology , gastroenterology , pharmacogenetics , genotype , biology , immunology , genetics , cytochrome p450 , metabolism , gene
Aims To determine CYP2C19 and CYP2D6 activity in patients with multiple sclerosis (MS) before and during interferon (IFN)‐β treatment. Methods CYP2C19 and CYP2D6 activities were assessed using the probe drugs mephenytoin and debrisoquine, respectively. Urinary mephenytoin (S/R) and debrisoquine (debrisoquine/hydroxy‐debrisoquine) metabolic ratios (MR) were determined in 10 otherwise healthy Caucasian multiple sclerosis (MS) patients in the initial stage of the disease, prior to and 1 month after commencing treatment with IFN‐β (Avonex, Rebif or Betaferon). In addition, CYP2C19 * 2, CYP2C19 * 3, CYP2D6 * 3, CYP2D6 * 4, and CYP2D6 * 5 genotyping was performed. Results There was no significant difference in the (S)/(R) mephenytoin ratio (mean difference 0.04; 95% CI −0.03, 0.11) or the debrisoquine MR (mean difference 0.29; 95% CI −0.44, 1.02) before and during regular IFN‐β treatment in extensive metabolizers (EM) ( P = 0.5 and P = 0.4 for the respective probe drugs; n = 9 subjects). There were also no differences between the different IFN‐β treatments ( P = 0.6 for the (S)/(R) mephenytoin ratio and P = 0.7 for the debrisoquine MR; anova ; n = 10). Conclusions IFN‐β treatment did not affect the activity of CYP2C19 or CYP2D6. The results suggest that it is safe to administer CYP2C19 or CYP2D6 substrates, without dose adjustment, to patients treated with IFN‐β.