Pharmacokinetics and pharmacodynamics of intrathecal ziconotide in chronic pain patients.
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.
Wermeling
Daniel
D
University of Kentucky Medical Center, Pain Treatment Center, Lexington, Kentucky, USA.
Drass
Michael
M
Ellis
David
D
Mayo
Martha
M
McGuire
Dawn
D
O'Connell
Damian
D
Hale
Victoria
V
Chao
Stella
S
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*
D018696:Neuroprotective Agents; D020960:omega-Conotoxins; C078452:ziconotide