Ethnic sensitivity study of fingolimod in white and Asian subjects.
Author(s): Kovarik JM, Slade A, Voss B, Schmidli H, Riviere GJ, Picard F, Sugita Y, Kawai R,
Mee-Lee D, Schmouder RL.
Affiliation(s): Novartis Pharmaceuticals, Basle, Switzerland. john.kovarik@Novartis.com
Publication date & source: 2007, Int J Clin Pharmacol Ther. , 45(2):98-109
OBJECTIVE: The authors compared the pharmacokinetics and pharmacological effects
of the immunomodulator fingolimod in healthy white and Asian subjects for
potential ethnic differences.
METHODS: White and Asian (Japanese) healthy subjects were demographically matched
for sex, age and weight. Subjects received single 1.25 mg doses of fingolimod (6
ethnic pairs), 2.5 mg (7 pairs), 5 mg (6 pairs) or 5 mg/day for 7 days (6 pairs).
The pharmacokinetics of fingolimod, major metabolites, peripheral blood
lymphocyte counts and heart rate were characterized over 1 month after
single-dose and 2 months after multiple-dose administration.
RESULTS: There were no clinically relevant differences in the fingolimod dose
Cmax or dose AUC relationships between Asian subjects (slopes 0.84 and 1.05)
versus white subjects (slopes 1.13 and 1.26) after single-dose administration.
During multiple-dose administration, there were no clinically relevant
interethnic differences in fingolimod accumulation ratios (6.6 +/- 0.4 for
whites, 7.0 +/- 0.7 for Asians), area under the concentration-time curve (390 +/-
73 versus 382 +/- 106 ng x h/ml), or elimination half-life (7.4 +/- 0.8 versus
7.9 +/- 2.0 days). The acute decrease in lymphocyte counts after single- and
multiple-dose fingolimod were similar in the two ethnic groups. The lymphocyte
recovery rate to baseline after a 5 mg single dose and 5 mg/day multiple dose was
reduced by 36 and 15% in Asian subjects compared with white subjects. The
transient, acute decrease in heart rate after the first dose of fingolimod and
the subsequent return to baseline was similar in the two ethnic groups.
CONCLUSION: There were no marked differences between healthy white and Asian
subjects in fingolimod single-dose and multiple-dose pharmacokinetics, lymphocyte
trafficking and heart rate responses.
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