Single- and Multiple-dose Pharmacokinetics of a Lorcaserin Extended-release Tablet.
Lorcaserin is a serotonin 2C receptor agonist indicated for chronic weight management as an adjunct to diet and exercise. The initial approved formulation is a 10-mg, immediate-release (IR) tablet for administration BID. These studies investigated the single- and multiple-dose pharmacokinetic properties of a new, recently US Food and Drug Administration-approved, extended-release, 20-mg once-daily formulation.



We performed 2 separate 2-period, 2-sequence crossover studies in 36 healthy adults: a study comparing the IR formulation to the extended-release formulation under fasting conditions and a study comparing the extended-release formulation under fed and fasted conditions.



Compared with lorcaserin IR, the Tmaxafter a single dose of lorcaserin extended-release was greater (median, 12 vs 3 hours), and the Cmaxwas 26% lower (38.8 vs 52.3 ng/mL). AUC data were bioequivalent for the 2 formulations in both single- and multiple-dose regimens, confirming no formulation effect on lorcaserin bioavailability. In fasted and fed conditions, Tmaxafter a single dose was identical (median, 12 hours), but Cmaxwas approximately 45% higher in the fed state (mean, 38.5 ng/mL fasted vs 56.1 ng/mL fed). However, at steady state, Cmaxand AUC were determined to be bioequivalent between the fasted and fed states, indicating no clinically relevant food effect on the pharmacokinetic properties of lorcaserin extended-release. The safety profile was consistent between the 2 formulations.



Overall, the results indicate that lorcaserin extended-release is a suitable once-daily alternative to the approved IR BID formulation.
Arena Pharmaceuticals, Inc, San Diego, California. Electronic address: rchristopher@arenapharm.com.
Ronald
R
Christopher
Arena Pharmaceuticals, Inc, San Diego, California.
Mike
M
Morgan
Eisai Inc, Woodcliff Lake, New Jersey.
Jim
J
Ferry
Eisai Inc, Woodcliff Lake, New Jersey.
Bhaskar
B
Rege
Arena Pharmaceuticals, Inc, San Diego, California.
Yong
Y
Tang
Eisai Inc, Woodcliff Lake, New Jersey.
Allan
A
Kristensen
Arena Pharmaceuticals, Inc, San Diego, California.
William
W
Shanahan
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001552:Benzazepines / Q000493:pharmacokinetics*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005215:Fasting; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013607:Tablets; D013810:Therapeutic Equivalency; D055815:Young Adult
D001552:Benzazepines; D003692:Delayed-Action Preparations; D013607:Tablets; C506658:lorcaserin
extended-release; lorcaserin; obesity; overweight; pharmacokinetic properties