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The safety of liposome bupivacaine following various routes of administration in animals

Joshi, Girish P ; Patou, Gary ; Kharitonov, Vladimir

Journal of pain research, 2015, Vol.8, p.781-789 [Peer Reviewed Journal]

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  • Title:
    The safety of liposome bupivacaine following various routes of administration in animals
  • Author: Joshi, Girish P ; Patou, Gary ; Kharitonov, Vladimir
  • Subjects: Drugs ; Drug delivery systems ; Safety and security measures ; Bupivacaine ; Analysis ; Anesthesia ; Dosage and administration ; Research ; Health aspects ; Vehicles ; Studies ; Pain ; Narcotics ; Analgesics ; Laboratories ; Lipids ; Bone surgery ; Drug dosages ; Pharmaceuticals ; spinal injections ; local anesthesia ; bupivacaine ; Original Research ; drug administration routes
  • Is Part Of: Journal of pain research, 2015, Vol.8, p.781-789
  • Description: This report presents results from four preclinical studies evaluating safety and pharmacokinetics (PKs) of liposome bupivacaine following intravascular (intravenous [IV], intra-arterial [IA]), epidural, and intrathecal administration in dogs. Intravascular administration was initially tested in a pilot study to determine maximum tolerated doses, and then in an expanded study of systemic adverse effects and PKs. An epidural study compared properties of liposome bupivacaine alone and in combination with lidocaine/epinephrine vs bupivacaine HCl. Another study assessed effects after intrathecal administration. In the initial intravascular studies, maximum doses at which no meaningful adverse events were observed with liposome bupivacaine were higher than for bupivacaine HCl (4.5 mg/kg IV vs 0.75 mg/kg IV, and 1.5 mg/kg IA vs 0.1 mg/kg IA, respectively). In the expanded intravascular study, there was no mortality or changes in pathology; adverse clinical signs included convulsions, lying on side, and decreased muscle tone (all were transient). In the epidural study, liposome bupivacaine was well tolerated at doses up to the highest dose tested (40 mg), with no evidence of spinal cord damage and with less motor blockade than bupivacaine HCl 15 mg. Intrathecal administration of liposome bupivacaine 40 mg was not associated with meaningful safety concerns and resulted in less motor blockade than bupivacaine HCl 15 mg. PK analyses showed that maximum plasma bupivacaine levels following administration of liposome bupivacaine (4.5 mg/kg IV and 40 mg epidural) were similar to maximum plasma bupivacaine levels following a threefold lower dose of bupivacaine HCl (1.5 mg/kg IV and 15 mg epidural). Liposome bupivacaine has a favorable safety profile compared with bupivacaine HCl when administered to dogs via intravascular, epidural, and intrathecal routes. This favorable safety profile is likely related to the liposome-bound nature of bupivacaine in the liposome bupivacaine formulation.
  • Publisher: New Zealand: Dove Medical Press Limited
  • Language: English
  • Identifier: ISSN: 1178-7090
    EISSN: 1178-7090
    DOI: 10.2147/JPR.S85424
    PMID: 26586964
  • Source: © ProQuest LLC All rights reserved

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