title: Bolus intrathecal injection of ziconotide (Prialt®) to evaluate the option of continuous administration via an implanted intrathecal drug delivery (ITDD) system: a pilot study.
abstract: OBJECTIVE
  This study evaluated efficacy and safety of bolus doses of ziconotide (Prialt®, Eisai Limited, Hertfordshire, UK) to assess the option of continuous administration of this drug via an implanted intrathecal drug delivery system.
  
  
  METHODS
  Twenty adults with severe chronic pain who were under consideration for intrathecal (IT) therapy were enrolled in this open label, nonrandomized, pilot study. Informed consent was obtained. Demographics, medical/pain history, pain scores, and concomitant medications were recorded. A physical examination was performed. Creatine kinase was measured. Initial visual analog scale (VAS), blood pressure, heart rate, and respiratory rate were recorded. All patients received an initial bolus dose of 2.5 mcg ziconotide; the dose in the subsequent visits was modified according to response. Subsequent doses were 2.5 mcg, 1.2 mcg, or 3.75 mcg as per protocol. A good response (≥30% reduction in baseline pain VAS) with no side-effects on two occasions was considered a successful trial. Data were analyzed using a generalized estimating equations model, with pain VAS as the outcome and time (seven time points; preinjection and one to six hours postinjection) as the predictor.
  
  
  RESULTS
  Generalized estimating equations analysis of summary measures showed a mean reduction of pain VAS of approximately 25% at the group level; of 11 responders, seven underwent pump implantation procedure, two withdrew because of adverse effects, one refused an implant, and one could not have an implant (lack of funding from the Primary Care Trust).
  
  
  CONCLUSIONS
  Our data demonstrated that mean VAS was reduced by approximately 25% at the group level after IT ziconotide bolus. Treatment efficacy did not vary with sex, center, age, or pain etiology. Ziconotide bolus was generally well tolerated. Larger studies are needed to determine if bolus dosing with ziconotide is a good predictor of response to continuous IT ziconotide via an intrathecal drug delivery system.
authors.affiliation: James Cook University Hospital, Middlesbrough, UK.
authors.forename: Salma I
authors.initials: SI
authors.lastname: Mohammed
authors.forename: Sam
authors.initials: S
authors.lastname: Eldabe
authors.forename: Karen H
authors.initials: KH
authors.lastname: Simpson
authors.forename: Morag
authors.initials: M
authors.lastname: Brookes
authors.forename: Grace
authors.initials: G
authors.lastname: Madzinga
authors.forename: Ashish
authors.initials: A
authors.lastname: Gulve
authors.forename: Ganesan
authors.initials: G
authors.lastname: Baranidharan
authors.forename: Helen
authors.initials: H
authors.lastname: Radford
authors.forename: Tracey
authors.initials: T
authors.lastname: Crowther
authors.forename: Eric
authors.initials: E
authors.lastname: Buchser
authors.forename: Christophe
authors.initials: C
authors.lastname: Perruchoud
authors.forename: Alan Mark
authors.initials: AM
authors.lastname: Batterham
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D059350:Chronic Pain / Q000188:drug therapy* / Q000209:etiology; D055111:Failed Back Surgery Syndrome / Q000150:complications / Q000188:drug therapy; D005260:Female; D006801:Humans; D015918:Infusion Pumps, Implantable / Q000009:adverse effects; D007278:Injections, Spinal; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy; D010147:Pain Measurement; D010865:Pilot Projects; D013997:Time Factors; D016896:Treatment Outcome; D020960:omega-Conotoxins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D018712:Analgesics, Non-Narcotic; D020960:omega-Conotoxins; C078452:ziconotide