(788) Topical morphine bioavailability in volunteersJ Paice, J Von Roenn, J Hudgins, L Luong, T Krejcie, M Avram; NorthwesternUniversity; Robert H. Lurie Comprehensive Cancer Center, Chicago, ILAlthough most patients with cancer-related pain obtain relief withavailable therapies, swallowing difficulties or intestinal obstruction pre-clude oral analgesic delivery. Topical morphine may provide an alter-nate delivery form but morphine bioavailability from a topical gel for-mulation has not been reported in humans. Therefore, we conducted arandomized, placebo controlled, double-blind, crossover study of fivehealthy volunteers after they provided institutionally approved writteninformed consent. They were admitted to the General Clinical ResearchCenter (GCRC) of Northwestern University twice, being randomly as-signed to receive either one mL of morphine compounded at 10 mg/mLin pluronic lecithin organogel (PLO) base (ExcelleRx, Philadelphia, PA)applied to the wrist and one mL of normal saline administered subcuta-neously or one mL of topical drug-free PLO base and one mL of subcu-taneous morphine 3 mg/mL on the first occasion and the opposite com-bination on the second occasion. Seventeen blood samples werecollected from 5 min to 10 h after dose administration for determinationof plasma morphine concentrations. Plasma samples were prepared bysolid-phase extraction and morphine concentrations measure by an LC-MS-MS technique with a linear range of 0.5 – 500 ng/ml. Bioavailabilityof the topical formulation was estimated from doses and areas underthe curves, assuming the subcutaneous dose bioavailability was 100%.The median bioavailability of morphine compounded in a PLO base andadministered topically to volunteers was less than 2%. Despite a reportthat topical morphine is effective in controlling chronic arthritis pain,the present results are consistent with the report that morphine wasminimally absorbed transdermally from a PLO formulation in dogs.These results suggest that transdermal administration of morphine com-pounded in a PLO base is unlikely to provide relief of cancer-relatedpain. Supported in part by a grant from ExcelleRx.

(789) An open-label pharmacokinetic study in humans of a4% amitriptyline 2% ketamine topical cream

D Everton, D Bhagwat, M Damask; EpiCept Corporation, Englewood Cliffs, NJTopically delivered pain medications can provide adequate pain reliefwithout the side-effects of systemically delivered drugs. This open-label,pharmacokinetic study in 36 healthy adults was designed to determineplasma levels of a topically delivered cream containing 4% amitriptylineand 2% ketamine (NP-1). The level of quantitation was (0.5 ng/mL). 4 mLof NP-1 cream were applied b.i.d. during a 48 hour period. Safety/toler-ability were assessed and blood samples were collected up to 96 hoursafter first application. Plasma amitriptyline levels were above 0.500ng/mL after the second application, through 60 hours after the lastapplication. The mean Cmax of 1.676 ng/mL occurred 72 hours after thefirst application. The highest amitriptyline concentration observed atany one time point was 5.91 ng/mL. The terminal elimination phase foramitriptyline had not been reached in most of the subjects. Plasmaketamine levels were above 0.500 ng/mL within several hours after thefirst application up to the last observation at 96 hours. The highest singleketamine concentration was 10.7 ng/mL. The mean ketamine Cmax of5.198 ng/mL occurred at 41.4 hours. Terminal elimination was ongoingduring the final 48 h of the study in the majority of the subjects. The PKparameter values for both drugs were age-group independent. NP-1was found to be safe and well tolerated across all groups. Mild, transientapplication site irritation was the most common adverse event and oc-curred in 11% of subjects. Prior studies utilizing a twice-daily local ap-plication of NP-1 in the treatment of various neuropathies suggest thatsignificant pain relief can be achieved. This study confirms that theefficacy is due to topical action as only sub-therapeutic blood levels ofboth drugs are observed.

(790) Effect of lidocaine patch on thermal thresholds andexperimental pain

M Wallace, V Lam, G Schulteis; University of California San Diego, La Jolla, CACurrently, there is a growing interest in the use of topical agents for thetreatment of pain; therefore, there is a need to validate the use ofhuman experimental pain using topical analgesics. This study evaluatedthe effects of topical lidocaine on intradermal capsaicin induced painand hyperalgesia. Thirteen subjects entered into a double-blind,placebo-controlled, randomized study. A baseline quantitative neuro-sensory test (QST) was performed on the volar aspect of each forearm. Aplacebo patch and a lidocaine patch was applied to the volar aspect ofeach forearm. The arms were randomized to placebo and lidocainepatch. After four hours of application the right forearm patch was re-moved, QST was repeated, and capsaicin (10�l, 10 mg/ml) was injectedintradermally at the site of application. Pain scores were measured atthe time of injection and every 2.5 minutes for 10 minutes. Ten minutesafter the capsaicin injection, the hyperalgesic area and flare responsewere mapped and QST was repeated. At the completion of the testingon the right forearm, the left forearm patch was removed and theprocedures described for the right forearm were repeated for the leftforearm. Prior to the capsaicin injection the lidocaine patch resulted in asignificant increase in the cool and warm thresholds and a significantdecrease in hot pain thresholds from baseline. There was no effect oncold pain thresholds. Although there was a trend for increase in touchand touch pain thresholds, it did not reach statistical significance. Thelidocaine patch had no effect on the pain, flare or hyperalgesia, Thisstudy demonstrated differential effects of the lidocaine patch on skinsensation. Since there was a lowering of the hot pain thresholds, it is notsurprising that lidocaine patch had no effect on intradermal capsaicininduced pain and hyperalgesia.

D30 - Other(791) Hyperbaric oxygen treatment decreases edema and me-

chanical hypersensitivity in animal models of acute in-flammation and arthritis

H. Wilson; University of Texas at Arlington, Arlington, TXSociety for Neuroscience abstract

S48 Abstracts