Comparison of the pharmacokinetics of an oral extended-release capsule formulation of carbidopa-levodopa (IPX066) with immediate-release carbidopa-levodopa (Sinemet(®)), sustained-release carbidopa-levodopa (Sinemet(®) CR), and carbidopa-levodopa-entacapone (Stalevo(®))

J Clin Pharmacol. 2015 Sep;55(9):995-1003. doi: 10.1002/jcph.514. Epub 2015 May 20.

Abstract

IPX066 (extended-release carbidopa-levodopa [ER CD-LD]) is an oral extended-release capsule formulation of carbidopa and levodopa. The single-dose pharmacokinetics of ER CD-LD (as 2 capsules; total dose, 97.5 mg-390 mg CD-LD) versus immediate-release (IR) CD-LD (25 mg-100 mg), sustained-release (CR) CD-LD (25 mg-100 mg), and CD-LD-entacapone (25 mg-100 mg-200 mg) was evaluated in healthy subjects. Following IR dosing, LD reached peak concentrations (Cmax ) at 1 hour; LD concentrations then decreased rapidly and were less than 10% of peak by 5 hours. With CR CD-LD and CD-LD-entacapone, LD Cmax occurred at 1.5 hours, and concentrations were less than 10% of peak by 6.3 and 7.5 hours, respectively. The initial increase in LD concentration was similar between ER CD-LD and IR CD-LD and faster than for CR CD-LD and CD-LD-entacapone. LD concentrations from ER CD---LD were sustained for approximately 5 hours and did not decrease to 10% of peak until 10.1 hours. Dose-normalized LD Cmax values for ER CD-LD were significantly lower (P< .05) than for the other CD-LD products. Bioavailability of LD from ER CD-LD was 83.5%, 78.3%, and 58.8% relative to IR CD-LD, CR CD-LD, and CD-LD-entacapone, respectively.

Keywords: IPX066; Parkinson's disease; extended release; levodopa; pharmacokinetics.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Antiparkinson Agents / administration & dosage
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / blood
  • Antiparkinson Agents / pharmacokinetics
  • Carbidopa / administration & dosage*
  • Carbidopa / adverse effects
  • Carbidopa / blood
  • Carbidopa / pharmacokinetics*
  • Catechols / administration & dosage*
  • Catechols / adverse effects
  • Catechols / pharmacokinetics*
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Drug Combinations
  • Female
  • Humans
  • Levodopa / administration & dosage*
  • Levodopa / adverse effects
  • Levodopa / blood
  • Levodopa / pharmacokinetics*
  • Male
  • Young Adult

Substances

  • Antiparkinson Agents
  • Catechols
  • Delayed-Action Preparations
  • Drug Combinations
  • Stalevo
  • carbidopa, levodopa drug combination
  • Levodopa
  • Carbidopa