This is a pilot, open label, single center study in 40 subjects undergoing bunionectomy. The study will assess and collect information on pharmacokinetics, pharmacodynamics, safety and efficacy of EXPAREL administered as a sciatic nerve block (in popliteal fossa).

A total of 10 subjects will be enrolled in each of the 4 cohorts.

Inclusion Criteria:

1. Healthy adult male or female volunteers ages 18 or older
2. American Society of Anesthesiologists (ASA) physical status 1, 2, or 3
3. Able to provide informed consent, adhere to the study schedule, and complete all study assessments.
4. Body Mass Index ≥18 and ≤40 kg/m2

Exclusion Criteria:

1. Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications for which an alternative is not named in the protocol (eg, amide-type local anesthetics, opioids, bupivacaine, NSAIDs)

2. Documented history of long-term diabetes or severe peripheral vascular disease

3. Renal (serum creatinine level >2mg/dL [176.8 μmol/L]) or hepatic dysfunction (serum alanine or aspartame transferase > 3 times the upper limit of normal).

4. Concurrent painful physical condition that may require analgesic treatment (such as long-term, consistent use of opioids) in the post dosing period for pain and which, in the investigator's opinion may confound the post dosing assessments

5. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years

6. Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study

7. Previous participation in an EXPAREL study

8. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the investigator, could interfere with study assessments or compliance

9. Currently pregnant, nursing, or planning to become pregnant during the study

10. Clinically significant medical disease that, in the opinion of the investigator, would make participation in a clinical study inappropriate. This includes any psychiatric or other conditions that would constitute a contraindication to participation in the study

11. Currently on neuroleptic agent [e.g., gabapentin, pregabalin (Lyrica), duloxetine (Cymbalta) etc.]

12. Inadequate sensory function on the foot (monofilament test)

13. Chronic opioid use in the last 30 days (≥30 morphine equivalents/ day)

    In addition, the subject may be withdrawn from the study if the subject meets the following criterion during or post-surgery:

14. Any clinically significant event or condition uncovered during the surgery (e.g., excessive bleeding, acute sepsis) that, in the opinion of the investigator, renders the subject medically unstable or complicates the subject's post-operative course