Pharmacokinetic studies of SEGLENTIS® (celecoxib and tramadol hydrochloride)1

Pharmacokinetic properties of SEGLENTIS1

In a Phase 1, randomized, single-dose, open-label, 4-period, 4-sequence, crossover absorption study at a single center in the United States, the following were compared:

The pharmacokinetics of 2 active pharmaceutical ingredients from SEGLENTIS with those of the individual reference products (used in the United States) alone or in free combination.

Pharmacokinetic parameters

Pharmkinetics chart Pharmkinetics chart

Treatment arms:

Arithmetic mean (%CV).

Celecoxib has been shown to be an inhibitor of CYP2D6 in in vitro studies.

Median (minimum, maximum).

n=32.

n=31.

n=28.

n=27.

n=21.

Tramadol concentration

To determine the mean plasma concentration-time profiles for tramadol and celecoxib after single-dose oral administration, patients in a 4-way cross-over study (male and female participants received all treatments in random order) received:

  • SEGLENTIS tablets
  • Tramadol hydrochloride IR tablets
  • Celecoxib capsule
  • Or tramadol hydrochloride IR tablets and celecoxib capsule administered concomitantly
Clock

Tramadol Tmax was 3.0 hours following administration of SEGLENTIS vs tramadol hydrochloride alone (2.0 hours) or coadministered with celecoxib (1.9 hours).1

Clipboard

Tramadol hydrochloride Cmax was 214 ng/mL following administration with SEGLENTIS vs tramadol hydrochloride alone (305 ng/mL) or coadministered with celecoxib (312 ng/mL).1

Treatment arms:

  • 200-mg SEGLENTIS (112-mg celecoxib/88-mg tramadol hydrochloride)
  • 100-mg tramadol hydrochloride IR
  • 100-mg celecoxib
  • 100-mg celecoxib + 100-mg tramadol hydrochloride IR (individual agents coadministered)

Celecoxib concentration

To determine the mean plasma concentration-time profiles for tramadol and celecoxib after single-dose oral administration, patients in a 4-way cross-over study (male and female participants received all treatments in random order) received:

  • SEGLENTIS tablets
  • Tramadol hydrochloride IR tablets
  • Celecoxib capsule
  • Or tramadol hydrochloride IR tablets and celecoxib capsule administered concomitantly
Clock

Celecoxib Tmax was 1.5 hours following administration of SEGLENTIS vs celecoxib alone (3.0 hours) and celecoxib in coadministration with tramadol (2.5 hours).1

Clipboard

Celecoxib Cmax was 259 ng/mL following administration with SEGLENTIS vs celecoxib alone (318 ng/mL) and celecoxib in coadministration with tramadol hydrochloride alone (165 ng/mL).1

Treatment arms:

  • 200-mg SEGLENTIS (112-mg celecoxib/88-mg tramadol hydrochloride)
  • 100-mg tramadol hydrochloride IR
  • 100-mg celecoxib
  • 100-mg celecoxib + 100-mg tramadol hydrochloride IR (individual agents coadministered)

AUC, area under the curve; Cmax, maximum drug concentration; IR, immediate release; t1/2, half-life; Tmax, time to Cmax.

Consistent observations of the pharmacokinetic profiles of SEGLENTIS components vs tramadol hydrochloride and celecoxib as individual agents or when coadministered*2

Treatment arms:

  • 200-mg SEGLENTIS (112-mg celecoxib/88-mg tramadol hydrochloride)
  • 100-mg tramadol hydrochloride IR
  • 100-mg celecoxib
  • 100-mg celecoxib + 100-mg tramadol hydrochloride IR (individual agents coadministered)

Cmax, maximum drug concentration; IR, immediate release; Tmax, time to Cmax.

Supportive pharmacokinetic data are consistent with label pharmacokinetic parameters: Single-dose, 4-way crossover, random-sequence study. Main pharmacokinetic parameters after oral administration of SEGLENTIS 2x 56-mg/44-mg tablet, 2x 50-mg tramadol IR capsules, 1x 100-mg celecoxib capsule, or tramadol IR capsules and celecoxib capsule administered concomitantly. Cmax and Tmax calculated using noncompartmental analysis.2

See how SEGLENTIS was evaluated in a Phase 3 study

Get important
SEGLENTIS updates

References

  1. SEGLENTIS [prescribing information]. Montgomery, AL: Kowa Pharmaceuticals America, Inc.; October 2021.
  2. Videla S, Lahjou M, Vaqué A, et al. Pharmacokinetics of multiple doses of co-crystal of tramadol-celecoxib: Findings from a four-way randomized open-label phase 1 clinical trial. Br J Clin Pharmacol. 2017;84(1):64-78. doi:10.1111/bcp.13428.