Absolute Bioavailability of Ponesimod, a Selective S1P1 Receptor Modulator, in Healthy Male Subjects.

Article Details

Citation

Copy to clipboard

Boehler M, Juif PE, Hoch M, Dingemanse J

Absolute Bioavailability of Ponesimod, a Selective S1P1 Receptor Modulator, in Healthy Male Subjects.

Eur J Drug Metab Pharmacokinet. 2017 Feb;42(1):129-134. doi: 10.1007/s13318-016-0325-6.

PubMed ID

26883438 [ View in PubMed

]

Abstract

BACKGROUND AND OBJECTIVES: The pharmacokinetic profile of ponesimod, a sphingosine-1-phosphate receptor 1 modulator, is characterized by a rapid absorption [time to maximum concentration (t max) of 2-4 h] and a terminal half-life (t (1/2)) of 32 h after single-dose administration. The aim of this study was to assess additional pharmacokinetic parameters [absolute bioavailability, total clearance (CL), and volume of distribution (V ss)] in healthy male subjects. METHODS: After ensuring in a pilot phase the full pharmacokinetic profile, safety, and tolerability of a 5-mg intravenous infusion of ponesimod over 3 h (treatment A), the study proceeded to the randomized, two-way crossover, single-dose (treatment A; treatment B: 10 mg oral) main phase. RESULTS: The absolute bioavailability of ponesimod was 83.8 % [90 % confidence interval (CI): 80.2-87.5]. CL and V ss (95 % CI) were 3.8 L/h (3.3-4.3) and 160 L (146.1-174.2), respectively. C max (95 % CI) was 48.5 ng/mL (43.9-53.6) and 61.4 ng/mL (55.3-68.3) after intravenous infusion and oral administration, respectively. The t (1/2) (95 % CI) following intravenous infusion was 32.9 h (28.5-38.1) and 31.7 h (27.9-36.0) following oral administration. Ponesimod administered by both routes of administration was well tolerated and resulted in transient decreases in lymphocyte count and heart rate. CONCLUSIONS: This study indicates high absolute bioavailability, low CL, and moderate V ss of ponesimod.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ponesimod	Sphingosine 1-phosphate receptor 1	Protein	Humans	Yes	Agonist Modulator Regulator	Details