David Rice1, Justin W Heil2, Lukasz Biernat3. 1. Division of Surgery, Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit Number: 1489, Room Number: FCT19.6000, Houston, TX, 77030, USA. 2. Naval Medical Center San Diego, 200 W. Arbor Drive, San Diego, CA, 92103, USA. 3. Medpace Clinical Pharmacology Unit, 5355 Medpace Way, Cincinnati, OH, 45227, USA. l.biernat@medpace.com.
Abstract
BACKGROUND:Liposomal bupivacaine is indicated for administration into the surgical site to produce post-surgical analgesia. OBJECTIVES: The objectives of this study were to characterize the pharmacokinetic and safety profiles of liposomal bupivacaine following a repeated dose in healthy volunteers. METHODS:Healthy adults were assigned to receive liposomal bupivacaine via subcutaneous infiltration in a single 266 mg dose (cohort 1) or in two 266 mg doses, with the second dose given immediately, 24, 48, or 72 h after the first dose (cohorts 2-5). Pharmacokinetic parameters were estimated from blood samples collected up to day 14. Subjects were monitored for adverse events and assessed for neurologic function, cardiac function, and infiltration area abnormalities. RESULTS:Twelve subjects were assigned to each cohort. The mean ± standard deviation maximum observed plasma concentration (C max) of bupivacaine after a single dose was 129 ± 47 ng/mL. The mean C max after the second dose was higher, but always less than double the C max for cohort 1. The highest individual C max (589 ng/mL) was observed in a subject who received the second dose 24 h after the first dose (cohort 4), but was well below the reported thresholds for neurotoxicity and cardiac toxicity (2000 and 4000 ng/mL, respectively). A single and repeated dose were well-tolerated, and there were no clinically meaningful findings regarding neurologic examinations and electrocardiography. CONCLUSIONS: The mean C max following a repeated dose of liposomal bupivacaine remained well below accepted values for central nervous system and cardiac toxicity. Liposomal bupivacaine was well-tolerated and revealed no clinically important safety signals. CLINICALTRIALS. GOV IDENTIFIER: NCT02210247.
RCT Entities:
BACKGROUND: Liposomal bupivacaine is indicated for administration into the surgical site to produce post-surgical analgesia. OBJECTIVES: The objectives of this study were to characterize the pharmacokinetic and safety profiles of liposomal bupivacaine following a repeated dose in healthy volunteers. METHODS: Healthy adults were assigned to receive liposomal bupivacaine via subcutaneous infiltration in a single 266 mg dose (cohort 1) or in two 266 mg doses, with the second dose given immediately, 24, 48, or 72 h after the first dose (cohorts 2-5). Pharmacokinetic parameters were estimated from blood samples collected up to day 14. Subjects were monitored for adverse events and assessed for neurologic function, cardiac function, and infiltration area abnormalities. RESULTS: Twelve subjects were assigned to each cohort. The mean ± standard deviation maximum observed plasma concentration (C max) of bupivacaine after a single dose was 129 ± 47 ng/mL. The mean C max after the second dose was higher, but always less than double the C max for cohort 1. The highest individual C max (589 ng/mL) was observed in a subject who received the second dose 24 h after the first dose (cohort 4), but was well below the reported thresholds for neurotoxicity and cardiac toxicity (2000 and 4000 ng/mL, respectively). A single and repeated dose were well-tolerated, and there were no clinically meaningful findings regarding neurologic examinations and electrocardiography. CONCLUSIONS: The mean C max following a repeated dose of liposomal bupivacaine remained well below accepted values for central nervous system and cardiac toxicity. Liposomal bupivacaine was well-tolerated and revealed no clinically important safety signals. CLINICALTRIALS. GOV IDENTIFIER: NCT02210247.
Authors: Joseph M Neal; Christopher M Bernards; John F Butterworth; Guido Di Gregorio; Kenneth Drasner; Michael R Hejtmanek; Michael F Mulroy; Richard W Rosenquist; Guy L Weinberg Journal: Reg Anesth Pain Med Date: 2010 Mar-Apr Impact factor: 6.288
Authors: Brigitte M Richard; Douglas E Rickert; Paul E Newton; Laura R Ott; Dean Haan; Abram N Brubaker; Phaedra I Cole; Paul E Ross; Marlon C Rebelatto; Keith G Nelson Journal: J Drug Deliv Date: 2011-10-05