title: Clinical Pharmacokinetics of IPX066: Evaluation of Dose Proportionality and Effect of Food in Healthy Volunteers.
abstract: OBJECTIVE
  IPX066 is an oral, extended-release capsule formulation of carbidopa-levodopa (CD-LD) available in 4 strengths. The goals of this investigation were to assess the dose proportionality of IPX066 and to study the effects of a high-fat, high-calorie meal and of sprinkling the capsule contents on applesauce on the pharmacokinetics of IPX066 in healthy volunteers.
  
  
  METHODS
  Three open-label studies were conducted. In the first study, subjects received 1 capsule of each IPX066 strength (23.75-95, 36.25-145, 48.75-195, and 61.25-245 mg of CD-LD). In the second study, subjects received 1 and 2 capsules of IPX066 245-mg LD under fasting conditions. In the third study, subjects received 2 capsules of IPX066 245-mg LD under 3 conditions: fasting; following a high-fat, high-calorie breakfast; and with the capsule contents sprinkled on applesauce under fasting conditions.
  
  
  RESULTS
  Peak plasma concentrations (Cmax) and systemic exposure (AUCt, AUCinf) for LD and CD increased dose-proportionally over the range of the IPX066 capsule strengths. Comparison of 1 and 2 IPX066 245-mg LD capsules showed dose-proportional pharmacokinetics for Cmax and AUCt. Sprinkling the capsule contents on applesauce did not affect the pharmacokinetics. A high-fat, high-calorie meal delayed the initial increase in LD concentration by approximately 1 to 2 hours, reduced Cmax by 21%, and increased AUCinf by 13% compared with the fasted state.
  
  
  CONCLUSIONS
  IPX066 shows dose-proportional pharmacokinetics. Sprinkling the capsule contents on applesauce does not affect the pharmacokinetics; a high-fat, high-calorie meal delayed absorption by 1 to 2 hours, slightly reduced Cmax, and slightly increased extent of absorption.
authors.affiliation: Impax Specialty Pharma, a Division of Impax Laboratories, Inc, Hayward, CA.
authors.forename: Hsuan-Ming
authors.initials: HM
authors.lastname: Yao
authors.forename: Ann
authors.initials: A
authors.lastname: Hsu
authors.forename: Suneel
authors.initials: S
authors.lastname: Gupta
authors.forename: Nishit B
authors.initials: NB
authors.lastname: Modi
mesh_terms: D000293:Adolescent; D000328:Adult; D000978:Antiparkinson Agents / Q000097:blood* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002230:Carbidopa / Q000097:blood* / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004562:Electrocardiography; D005215:Fasting / Q000097:blood; D005260:Female; D064368:Healthy Volunteers; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D057913:Joint Capsule Release; D007980:Levodopa / Q000097:blood* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D013997:Time Factors; D055815:Young Adult
chemical_list: D000978:Antiparkinson Agents; D004338:Drug Combinations; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D002230:Carbidopa