[A phase II clinical study of once-a-day fentanyl citrate patch in patients with cancer pain--switching from once-every-three-days fentanyl patch to once-a-day fentanyl citrate patch].

We examined the efficacy and safety of a new transdermal fentanyl citrate patch (HFT-290), which was applied once daily in patients with cancer pain who were receiving a stable dose of once-every-three-day application transdermal fentanyl patch [TDF (72 hr)]. After TDF (72 hr) was applied for three days at the same dose used before starting the study, treatment was switched to HFT-290 (once daily) for 9 days. The analgesic effect was judged with a 5-point scale based on each patient's assessment of pain on a 100-mm visual analog scale (VAS). Seventy-eight patients were enrolled. The efficacy rate (95% confidence interval) of the analgesic effect at the time of final removal of HFT-290 (the primary efficacy end-point) was high at 83.9% (71.7-92.4%; 47/56 patients). Furthermore, based on the shift of the VAS, good pain control was achieved after switching. All adverse drug reactions were either mild or moderate, and the main reactions were those commonly observed with opioid analgesics. No respiratory depression was observed. HFT-290 demonstrated good tolerability after switching from TDF (72 hr) and provided stable pain control.

[The effects of early nerve blocks for prevention of postherpetic neuralgia and analysis of prognostic factors].

BACKGROUND: Herpes zoster causes acute pain and sometimes leads to postherpetic neuralgia (PHN). The previously reported risk factors of PHN such as old age, allodynia, paresthesia and so on are not based on evidence. Although nerve block is useful to relieve acute pain and recommended for prevention of PHN, evidence is scanty. METHODS: The patients with herpes zoster within 3 months after the onset were studied. The patient underwent nerve blocks and proper medical treatment, and were followed for up to one year. The risk factors of PHN were assessed. We evaluated whether nerve block prevented PHN. RESULTS: A total of 144 consecutive patients were studied. Twenty seven % of patients suffered PHN. Old age (> 65 y. o) and hypesthesia were confirmed to be the risk factors of PHN, whereas the intensity of acute pain was not. Patients who underwent nerve block within 1 month after the onset were less likely to suffer from PHN compared with patients of delayed nerve blocks. CONCLUSIONS: Old age, hypesthesia and delayed nerve blocks were the risk factors of PHN. Nerve blocks in the early phase of herpes zoster may be useful to prevent PHN, particularly in the younger patients.

Efficacy, safety and pharmacokinetic study of a novel fentanyl-containing matrix transdermal patch system in Japanese patients with cancer pain.

BACKGROUND AND OBJECTIVES: A novel transdermal matrix patch delivery system for fentanyl has been developed to deliver improved management of cancer pain compared with that obtained using current fentanyl reservoir patches. This study was carried out to assess the efficacy, safety and pharmacokinetic profiles of a 12.5 microg/h transdermal matrix fentanyl patch administered with the objective of replacing morphine, oral oxycodone or fentanyl injection formulations. The study also evaluated how the pharmacokinetic profiles of higher dose fentanyl patches (25, 37.5 and 50 microg/h) changed following dose adjustments to optimize management of cancer pain. METHODS: This open-label, multicentre study involved 87 patients of both sexes (> or =20 years) with a confirmed diagnosis of cancer. Patients were receiving any one of the following at the time of enrollment for the management of their cancer pain: (a) morphine <45 mg/day orally, <30 mg/day as suppositories, or <15 mg/day by injection; (b) oral oxycodone <30 mg/day; or (c) fentanyl injectable preparations <0.3 mg/day. The patients were administered a 3-day course of fentanyl transdermal matrix patch application three times. The initial dose was 12.5 microg/h, which could be increased when a new patch was applied if the physician deemed this to be appropriate based on pain intensity ratings and use of rescue medications. Efficacy outcomes included patients' global assessment scores (primary efficacy endpoint) measured on a five-step scale and dichotomous scores for physicians' global assessment. The occurrence of adverse events and changes in laboratory tests were evaluated as safety variables. Serum fentanyl levels were measured immediately after removal of the old patch on days 4, 7 and 10 to obtain data on trough serum concentrations. RESULTS: The percentage of patients in category 3 or higher (very satisfied, satisfied, or neither satisfied nor dissatisfied) for the patient's global assessment score was 89.4% (76/85), indicating high patient satisfaction and attainment of sufficient pain control after patients switched from their previously used opioid analgesics. Similar findings were obtained on physicians' global assessment scores. A total of 316 adverse events occurred in 78 (90.7%) of 86 patients who were administered at least one patch. These included nausea (31 [36.0%]), somnolence (26 [30.2%]), vomiting (22 [25.6%]), diarrhoea (17 [19.8%]), constipation (14 [16.3%]), pyrexia (11 [12.8%]) and insomnia (9 [10.5%]). The mean (+/- SD) serum fentanyl concentration determined on day 4 was 169.9 +/- 103.4 pg/mL (n = 83). Serum fentanyl measurement results indicated that the same fentanyl patch dose resulted in similar serum fentanyl levels, while increased doses produced higher serum fentanyl concentrations. CONCLUSION: The fentanyl matrix transdermal patch formulation employed in this study demonstrated sufficient cancer pain control for patients switching from morphine or oral oxycodone preparations. The patch tested was well tolerated and its use did not result in any increased incidence of adverse drug reactions over those commonly found with opioid analgesics.

[Usefulness of fentanyl patch (Durotep) in cancer patients when rotated from morphine preparations].

BACKGROUND: [corrected] The transdermal fentanyl patch (Durote patch) is an opioid preparation requiring replacement once in three days, which is occasionally prescribed to replace morphine preparations. The conversion ratio from morphine to fentanyl has been claimed to be 100:1 or 150:1, but there may exist individual variations. METHODS: We retrospectively evaluated the analgesic effects and adverse effects of fentanyl patch in 24 cases among 22 patients (11 men and 11 women). RESULTS: There were some reasons for switching; the major one was for home-care. In most cases rotation was completed in a few days and the side effects disappearance or were reduced, but 4 cases of them showed severe diarrhea or exhibited exacerbation of the pain, and had to go back to morphine. There were a wide variations of conversion ratio with a mean of 96.6. CONCLUSIONS: The fentanyl patch is a useful agent to control severe cancer pain because of excellent analgesic effect, less adverse effects and more convenience as well as itsundesirable characteristics when transition of patients to home-care is considered or oral administration should be avoided. Above all it offers a great possibility to improve cancer patient's quality of life.

[A case of intractable lower limb pain treated successfully by spinal cord stimulation with an electrode inserted retrogradely].

We experienced a case of intractable lower limb pain successfuly treated by spinal cord stimulation with an electrode inserted retrogradely. The patient is a 32 year-old-man suffering from intractable lower limb pain on the area innervated by the sciatic nerve from unidentified cause for about 4 years. We tried various treatments such as epidural block, S 1 nerve-root block including thermocoagulation technique, opiate. Nevertheless, his pain became worse further. Therefore, 6 years after the onset of the symptom, we tried to stimulate electrically the nerve with an electrode inserted retrogradely. This method of spinal cord stimulation produced enough pain reduction. The method of retrograde insertion of an electrode for spinal cord stimulation seems to be a good way to treat intractable pain of the area innervated by a single spinal nerve.

[Sensory nerve anesthesia with 4% liposomal lidocaine cream in healthy subjects by use of the neuroselective current perception threshold].

BACKGROUND: ELA-Max, an external liposomal preparation of lidocaine (4%) available without prescription in United States, has a recommended application time of 15 to 45 min without occlusive dressing, and the side effect has been reported to be rare. To investigate external anesthetic preparations to reduce neuropathic pain, we evaluated sensory nerve anesthesia by ELA-Max in comparison with placebo and other lidocaine topical preparations by double blind method. METHODS: We measured the neuroselective current perception threshold (N-CPT) 30 min after the application of ELA-Max on 30 healthy Japanese volunteers. Evaluation of anesthetic effect was performed by change in N-CPT rate before and after the application of 0.025 g x cm(-2) to the skin where stimulation was performed. RESULTS: ELA-Max increased N-CPT ratio in 4 out of 9 subjects stimulated at 5 Hz. However these CPT values were within normal ranges, and the change in N-CPT ratio was not statistically significant throughout all stimulation frequencies. CONCLUSIONS: The application of 0.025 g x cm(-2) ELA-Max for 30 min was not effective to induce therapeutic level of anesthesia. Extended application times as well as occlusive dressing may be needed for this preparation to be used clinically.

Substance P receptor in U373 MG human astrocytoma cells activates mitogen-activated protein kinases ERK1/2 through Src.

Substance P (SP) acting through substance P receptor (SPR) increases the proliferation of glioblastoma cells. At the molecular level, stimulation of SPR in human U373 MG glioblastoma cells results in phosphorylation of mitogen-activated protein kinases ERK1/2. Examination of the underlying mechanism reveals that SPR mediates ERK1/2 phosphorylation in a calcium-dependent manner. Surprisingly, blockade of epidermal growth factor receptor (EGFR), which is transactivated by SPR, has a minimal effect on SPR-mediated ERK1/2 phosphorylation. However, SPR-mediated ERK1/2 phosphorylation is significantly reduced by the Src kinase inhibitor PP2. Interestingly, ERK1/2 in U373 MG cells is also activated by several other mitogenic G protein-coupled receptors (GPCRs) including alpha(1B)-adrenergic, M(3)-muscarinic, and H(1)-histaminergic in an Src-dependent manner. We conclude that c-Src is a mediator of SP-stimulated ERK1/2 phosphorylation in human U373 MG glioblastoma cells.