S54 (317) Oral diclofenac potassium liquid filled soft gelatin capsule (DPSGC) reduces opioid use in patients recovering from bunionectomy D Riff, S Duckor, I Gottlieb, E Diamond, G Raymond, S Boesing; Advanced Clinical Research Institute, Anaheim, CA Patients undergoing bunionectomy can experience moderate to severe pain that is often managed with opioids. Minimizing opioid-induced adverse events via decreased opioid exposure while maintaining adequate pain relief is an important clinical challenge. Here we present the opioidsparing capacity of DPSGC 25 mg (ZipsorÔ, Xanodyne Pharmaceuticals, Inc, Newport, KY), an investigational, low-dose, liquid filled, gelatin capsule formulation of diclofenac potassium. This was a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study in patients with pain following first metatarsal bunionectomy. Patients were randomized to receive DPSGC 25 mg (n = 102) or placebo (n = 99) on the day following surgery after experiencing a requisite level of pain ($ 4 based on an 11-point numeric pain rating scale [NPRS]; 0 = no pain, 10 = worst pain possible). The second dose of study drug was administered when the patient felt it necessary to treat their pain. Subsequent doses were administered every 6 hours throughout a 48-hour multipledose inpatient period. After the second dose, opioid rescue medication (hydrocodone 5 mg with acetaminophen 500 mg) was available as needed. Results indicated that fewer patients receiving DPSGC required rescue medication on Day 1 and Day 2 compared with those receiving placebo (39% vs 88% on Day 1; 22% vs 65% on Day 2; P < .0001). Mean interval time to rescue medication use between study drug doses was significantly longer for patients receiving DPSGC 25 mg than placebo (332 minutes vs 264 minutes; P < .0001). Among those who did use rescue medication, the mean number of administrations was significantly less in patients receiving DPSGC (1.93) than in those receiving placebo (2.37) on Day 1 (P < .05). DPSGC was well tolerated with no serious adverse events being reported. DPSGC 25 mg reduced the need for opioids in patients recovering from bunionectomy compared with placebo. (Supported by Xanodyne Pharmaceuticals, Inc.)
D20 Preemptive Analgesia (318) Do prior painful experiences affect infant biobehavioral pain response? L Hatfield, L Whaley, A Dyer; University of Pennsylvania, Philadelphia, PA Multiple lines of evidence suggest pain experienced early in life may contribute to permanent alterations in the newborn central nervous system. Previous studies found infants who did not receive analgesia prior to painful procedures experienced greater duration and intensity of cry during immunizations compared to infants that received preemptive analgesia. To determine the effect of neonatal circumcision on biobehavioral pain response during immunizations, a randomized, placebo-controlled clinical trial at an ambulatory pediatric clinic was conducted. Between May and July 2005 forty healthy term infants scheduled to receive routine 2 and 4-month immunizations were randomized to receive 24% oral sucrose or sterile water 2 minutes before immunizations. Data analysis for the study was limited to circumcised male infants (n = 22). Parents affirmed analgesia administration during their son’s circumcision. The University of Wisconsin Children’s Hospital pain scale measured serial acute behavioral pain responses at baseline, 2 and 5 minutes following solution administration among infants randomized to receive 24% sucrose (n = 12) or sterile water (n = 10). Repeated measures ANOVA examined between-group differences and within-subject variability of the effects of analgesia prior to circumcision on overall behavioral pain scores. At each time point (2 and 5 minutes) within each treatment group (sucrose and sterile water), no statistically significant differences were found in behavioral pain score for male infants who did and did not receive analgesia prior to circumcision: sucrose, 2 minutes (P = 0.9998); sucrose, 5 minutes (P = 0.9905); placebo, 2 minutes (P = 0.8560); placebo, 5 minutes (P = .6223). Although lack of statistical significance may be influenced by small sample size, the data suggest for male infants, preemptive analgesia during neonatal circumcision has no significant effect on biobehavioral pain response during routine immunizations at 2 and 4 months of age. (Support: Children’s Miracle Network.) This abstract will also be presented as an Oral Paper Presentation. Refer to the daily Schedule-At-A-Glance for presentation time and location.
D21 Spinal Analgesia (319) Comparison of intravenous, epidural and intrathecal administration of methadone in a rat model S Haroutiunian, I Yifrah, A Hoffman; The Hebrew University of Jerusalem, Jerusalem, Israel Methadone is a synthetic opioid used systemically for chronic pain treatment. Epidural and intrathecal administration of methadone are reported in humans, however; it is still uncertain whether they are superior to systemic administration. This question led us to compare the pharmacodynamic effects of intravenous (iv), epidural and intrathecal administration of methadone in a rat model. Male Sprague-Dawley rats (weight 250-300g) were used. For iv drug administration, the right jugular vein of the rats was catheterized. For epidural and intrathecal administration, a skin incision and muscle dissection were made at midline L1-L2 level. The inervertebral ligament was cut and a PE-10 catheter was inserted 1.5 cm caudally either epidurally or intrathecally, and tunneled to the dorsal neck area. The administered volume of racemic methadone solution was 400ml iv and 35ml epidurally or intrathecally. The effect of 0.25 mg/kg methadone by each route was investigated using both tail-withdrawal test and by tail-flick test. The time to tail-withdrawal was measured. The cumulative analgesic effect (CAE) of methadone was measured by calculating the area under the curve of % maximal possible effect (MPE) plot against time. The CAEs for epidural and intrathecal methadone (1040064708 and 1162663514, respectively), by tail-withdrawal test, were significantly higher compared to iv methadone (18286799), p<0.05. By tail-flick test, the CAE of intrathecal methadone (1475861920) was significantly higher compared to iv methadone (27176146), p<0.01. The difference between CAE of epidural (897962978) and iv methadone appear to exist, but did not reach statistical significance. These experiments suggest that intrathecal and epidural administration of methadone provides more significant analgesia compared to intravenous administration in a rat model. No significant difference in effect between intrathecal and epidural administration was observed.
(320) Real-world practice patterns and costs in patients with low back pain R Swindle, H Birnbaum, J Ivanova, M Hsieh, M Schiller, C Sigal; Eli Lilly and Company, Indianapolis,IN Treatment guidelines suggest that most low back pain (LBP) resolves within a few weeks and that immediate use of imaging and aggressive therapies should be avoided. We assess the actual practice patterns of imaging, noninvasive therapy, medication, and surgery in LBP patients and compare their costs to those of matched non-LBP controls. The 211,551 patients, ages 18-64 years, with >1 LBP HEDIS diagnosis, between 2002 and 2006, were identified from a large administrative claims database. Patients were required to have continuous eligibility >12 months after their index LBP diagnosis (study period) and >6 months before their index diagnosis (baseline period) and no other LBP diagnosis during the baseline period. LBP patients were matched to a random cohort of non-LBP patients by age, gender, and employment status. Univariate analyses described treatment patterns and compared baseline characteristics and 12month costs. Patients with LBP had significantly higher rates of baseline comorbidities and resource use compared with controls. 47.7% of LBP patients had imaging soon after LBP diagnosis (mean: 34 days; median: 0 days). The majority of LBP patients (69.8%) used medications (mean: 52 days; median:8 days). Opioids were most commonly prescribed (42.1%). 2.05% of patients with LBP had surgery during the study period (mean: 122 days; median: 90 days) after LBP diagnosis. LBP patients were likely to have chiropractic therapy first, followed by muscle relaxants and NSAIDs. LBP patients had significantly higher direct costs compared with controls ($7,211 vs. $2,382, respectively; P < .001), with surgery patients contributing $33,931 in direct costs. Contrary to clinical guidelines, many patients with LBP start incurring significant resource use and as a result, incur expense soon after index diagnosis. LBP is associated with a significant and early cost burden. (Research funding provided by Eli Lilly.)