title: Pharmacokinetics and pharmacodynamics of intrathecal ziconotide in chronic pain patients.
abstract: The pharmacokinetics and pharmacodynamics of ziconotide were assessed over a 48-hour period following intrathecal (i.t.) administration (1, 5, 7.5, or 10 micrograms) to 22 patients with chronic, nonmalignant pain. Plasma and cerebrospinal fluid (CSF) samples were obtained over a 24-hour period. Analgesic efficacy was monitored using Visual Analog Scale of Pain Intensity (VASPI) and Category Pain Relief Scores (CPRS) measurements. Pharmacokinetic (PK) parameters were calculated by noncompartmental methods. Plasma ziconotide data were insufficient for PK calculations. In CSF, the median half-life of ziconotide was 4.5 hours. The median CSF clearance and volume of distribution were 0.26 mL/min and 99 mL, respectively. CSF pharmacokinetics of ziconotide were linear, based on cumulative exposure and peak CSF concentrations. A dose-related analgesia was observed. Pharmacokinetic-pharmacodynamic efficacy and safety analyses showed that higher CSF ziconotide concentrations were generally associated with analgesia and increased incidence of nervous system adverse events following a 1-hour i.t. infusion.
authors.affiliation: University of Kentucky Medical Center, Pain Treatment Center, Lexington, Kentucky, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wermeling
authors.forename: Michael
authors.initials: M
authors.lastname: Drass
authors.forename: David
authors.initials: D
authors.lastname: Ellis
authors.forename: Martha
authors.initials: M
authors.lastname: Mayo
authors.forename: Dawn
authors.initials: D
authors.lastname: McGuire
authors.forename: Damian
authors.initials: D
authors.lastname: O'Connell
authors.forename: Victoria
authors.initials: V
authors.lastname: Hale
authors.forename: Stella
authors.initials: S
authors.lastname: Chao
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D016683:Supine Position; D020960:omega-Conotoxins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D020960:omega-Conotoxins; C078452:ziconotide