title: Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel.
abstract: OBJECTIVE
  Abraxane (ABI-007) is a 130-nm albumin-bound (nab) particle formulation of paclitaxel, devoid of any additional excipients. We hypothesized that this change in formulation alters the systemic disposition of paclitaxel compared with conventional solvent-based formulations (sb-paclitaxel; Taxol), and leads to improved tolerability of the drug.
  
  
  METHODS
  Patients with malignant solid tumors were randomized to receive the recommended single-agent dose of nab-paclitaxel (260 mg/m(2) as a 30-minute infusion) or sb-paclitaxel (175 mg/m(2) as a 3-hour infusion). After cycle 1, patients crossed over to the alternate treatment. Pharmacokinetic studies were carried out for the first cycle of sb-paclitaxel and the first two cycles of nab-paclitaxel.
  
  
  RESULTS
  Seventeen patients were treated, with 14 receiving at least one cycle each of nab-paclitaxel and sb-paclitaxel. No change in nab-paclitaxel pharmacokinetics was found between the first and second cycles (P = 0.95), suggesting limited intrasubject variability. Total drug exposure was comparable between the two formulations (P = 0.55) despite the dose difference. However, exposure to unbound paclitaxel was significantly higher after nab-paclitaxel administration, due to the increased free fraction (0.063 +/- 0.021 versus 0.024 +/- 0.009; P < 0.001).
  
  
  CONCLUSIONS
  This study shows that paclitaxel disposition is subject to considerable variability depending on the formulation used. Because systemic exposure to unbound paclitaxel is likely a driving force behind tumoral uptake, these findings explain, at least in part, previous observations that the administration of nab-paclitaxel is associated with augmented antitumor efficacy compared with solvent-based paclitaxel.
authors.affiliation: Clinical Pharmacology Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute-Frederick, Frederick, Maryland, USA.
authors.forename: Erin R
authors.initials: ER
authors.lastname: Gardner
authors.forename: William L
authors.initials: WL
authors.lastname: Dahut
authors.forename: Charity D
authors.initials: CD
authors.lastname: Scripture
authors.forename: Jacquin
authors.initials: J
authors.lastname: Jones
authors.forename: Jeanny B
authors.initials: JB
authors.lastname: Aragon-Ching
authors.forename: Neil
authors.initials: N
authors.lastname: Desai
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hawkins
authors.forename: Alex
authors.initials: A
authors.lastname: Sparreboom
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002277:Carcinoma / Q000188:drug therapy*; D018592:Cross-Over Studies; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012997:Solvents / Q000737:chemistry*
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D000972:Antineoplastic Agents, Phytogenic; D012997:Solvents; D017239:Paclitaxel