Pharmacokinetics and Safety of Bupivacaine HCl Spinal Block and EXPAREL Local Infiltration in Total Knee Arthroplasty

Inclusion Criteria: 1. Males or females ≥18 years of age. 2. American Society of Anesthesiologists (ASA) physical status 1, 2, or 3. 3. Scheduled to undergo spinal block in conjunction with unilateral TKA. 4. Female subjects must be surgically sterile, at least 2 years postmenopausal, or using a medically acceptable method of birth control. Females of childbearing potential must have a documented negative blood or urine pregnancy test result within 24 hours before surgery. 5. Able to provide informed consent, adhere to the study schedule, and complete all study assessments. Exclusion Criteria: 1. History of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics or opioids. 2. Contraindication to bupivacaine. 3. Received bupivacaine or any other local anesthetic within 7 days of EXPAREL administration. 4. Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after EXPAREL administration. 5. Planned concurrent surgical procedure (e.g., bilateral TKA). 6. Body weight \<50 kg (110 pounds) or a body mass index ≥45 kg/m2. 7. Received any investigational drug within 30 days prior to EXPAREL administration, and/or has planned administration of another investigational product or procedure during the subject's participation in this study. 8. Previous participation in an EXPAREL study. 9. Malignancy in the last 2 years, with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix. 10. Current or historical evidence of any clinically significant disease or condition, especially cardiovascular or neurological conditions that, in the opinion of the Investigator, may increase the risk of surgery or complicate the subject's postsurgical course. 11. Clinically significant medical or psychiatric disease that, in the opinion of the Investigator, would constitute a contraindication to participation in the study, or cause inability to comply with the study requirements. In addition, the subject will be ineligible to receive EXPAREL if he or she meets the following criteria during surgery: 12. Any clinically significant event or condition uncovered during the surgery (e.g., excessive bleeding, acute sepsis) that might render the subject medically unstable or complicate the subject's postsurgical course.