Abstract ID: A47

Abstract Title: The Pharmacokinetic Profile of an Extended-Release Liposomal Formulation of Bupivacaine Administered via a Single Epidural Injection

Authors: Ludbrook G1, Ardeleanu M2, Manvelian G3, Rashti N4
         University of Adelaide Adelaide South Australia Australia1, SkyePharma Inc. San Diego CA USA2, SkyePharma Inc. San Diego CA USA3, SkyePharma Inc. San Diego CA USA4
Poster Type: Either


ABSTRACT BODY

Background and Goal of Study:
SKY0402 is a liposomal formulation of bupivacaine developed for the management of post-operative pain (POP). In this study, the pharmacokinetic profile of SKY0402 was compared with that of a commercially-available bupivacaine HCl solution (i.e., MarcainŽ 0.25%).

Materials and Methods:
This is a Phase 1, double-blind study, in which 20 healthy volunteers were randomized within sequential cohorts to receive SKY0402 (100 mg in Cohort 1 and 175 mg in Cohort 2) or Marcain 50 mg, via a single epidural injection. Plasma samples were collected and analyzed for bupivacaine concentration through 96 hours post-dose. The study has a dose-escalation, sequential cohort design and is currently ongoing. Data from the first two cohorts are reported below.

Results and Discussions:
Bupivacaine plasma concentrations peaked lower, later, and took longer to decline in the SKY0402 groups compared with the Marcain group (Figure 1). Less than dose-proportional increase in C-max was observed for the 175-mg dose compared with the 100- mg dose of SKY0402. Both SKY0402 dose-levels investigated (100 mg and 175 mg) produced peak plasma concentrations significantly lower than a 50-mg dose of Marcain. Systemic exposure to bupivacaine, based on AUC0-last was proportional with the dose of bupivacaine administered (Table 1). The dose-adjusted AUC(0-last) were comparable among the study groups.

Conclusion:
The pharmacokinetic profile of SKY0402 was consistent to that of a sustained-release formulation.

ATTACHED FILES

A47_C-103 PK Cohort 1+2 (060106)-Figure 1.doc

A47_C-103 PK Cohort 1+2 (060106)-Table 1.doc



Reg Anesth Pain Med 2005; 30(3):A47