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.

Lidocaine patch 5% with systemic analgesics such as gabapentin: a rational polypharmacy approach for the treatment of chronic pain.

OBJECTIVE: To assess the effectiveness and safety of the lidocaine patch 5%, a targeted peripheral analgesic, in the treatment of postherpetic neuralgia, painful diabetic neuropathy, and low back pain patients with incomplete responses to their current analgesic treatment regimen containing gabapentin. DESIGN: This was a 2-week, open-label, nonrandomized, multicenter pilot trial in the clinical setting. Patients with postherpetic neuralgia, painful diabetic neuropathy, or low back pain with partial responses (average daily pain intensity >4/10) to their current analgesic treatment regimen were included. Treatment consisted of daily application of up to four lidocaine patches to areas of maximal peripheral pain. Effectiveness was evaluated using the Brief Pain Inventory (BPI). Safety was assessed by adverse events, physical and neurologic examinations, vital signs, and clinical laboratory tests. RESULTS: Significant improvements in BPI measures of pain intensity and pain relief were reported for all groups of patients after 2 weeks of lidocaine patch 5% treatment. Significant improvements in BPI measures of pain interference with general activity, mood, walking ability, normal work, relationships with others, sleep, and enjoyment of life were noted. The lidocaine patch 5% was found to be safe and well tolerated. CONCLUSIONS: Results of this study highlight the potential advantages achieved with rational polypharmacy using a targeted peripheral analgesic, the lidocaine patch 5%, with centrally acting agents such as the anticonvulsant gabapentin. Controlled trials are warranted to further define the impact of such combination therapy.