Development and Evaluation of Orodispersible Tablets Containing Ketoprofen.

BACKGROUND: Orodispersible Tablets (ODTs) are an option to facilitate the intake of pharmaceutical solid dosage forms, which dissolve in the mouth within 30 seconds releasing the drug immediately with no need for water intake or chewing. OBJECTIVE: The main goal of our study is the technological development of lactose-free orodispersible tablets that contain ketoprofen. METHODS: We assessed different variables during the pharmaceutical development of ODTs: compression techniques conducted after a wet granulation process, aiming to optimize the flow properties of the formulation, and a suspension freeze-drying molded in blisters. We developed three formulations for each method, each containing one of the superdisintegrants: croscarmellose, crospovidone, or starch glycolate. RESULTS: During the production of ODTs, we performed quality control of the granulation process, since the production of pellets contributed to the enhancement of the disintegration time and content homogeneity. Quality control tests for ODTs produced by freeze-drying were also satisfactory, despite significant changes in the final physical aspect of these products when compared to that of ODTs produced by compression. In addition, the disintegration times of ODTs produced by freeze-drying were substantially higher. Furthermore, these tablets displayed greater friability and pose a challenge to the control of a standard individual weight. CONCLUSION: Among the superdisintegrants, croscarmellose contributed most significantly to reduce the disintegration time and to dissolve KTP effectively in 20 minutes.

Assessment of a carbon dioxide laser for the measurement of thermal nociceptive thresholds following intramuscular administration of analgesic drugs in pain-free female cats.

OBJECTIVE: To assess the potential of a thermal carbon dioxide (CO2) laser to explore antinociception in pain-free cats. STUDY DESIGN: Experimental, prospective, blinded, randomized study. ANIMALS: Sixty healthy adult female cats with a (mean±standard deviation) weight of 3.3±0.6 kg. METHODS: Cats were systematically allocated to one of six treatments: saline 0.2 mL per cat; morphine 0.5 mg kg(-1); buprenorphine 20 µg kg(-1); medetomidine 2 µg kg(-1); tramadol 2 mg kg(-1), and ketoprofen 2 mg kg(-1). Latency to respond to thermal stimulation was assessed at baseline and at intervals of 15-30, 30-45, 45-60, 60-75, 90-105 and 120-135 minutes. Thermal thresholds were assessed using time to respond behaviourally to stimulation with a 500 mW CO2 laser. Within-treatment differences in response latency were assessed using Friedman's test. Differences amongst treatments were assessed using independent Kruskal-Wallis tests. Where significant effects were identified, pairwise comparisons were conducted to elucidate the direction of the effect. RESULTS: Cats treated with morphine (χ2=12.90, df=6, p=0.045) and tramadol (χ2=20.28, df=6, p=0.002) showed significant increases in latency to respond. However, subsequent pairwise comparisons indicated that differences in latencies at specific time-points were significant (p<0.05) only for tramadol at 60-75 and 90-105 minutes after administration (21.9 and 43.6 seconds, respectively) in comparison with baseline (11.0 seconds). No significant pairwise comparisons were found within the morphine treatment. Injections of saline, ketoprofen, medetomidine or buprenorphine showed no significant effect on latency to respond. CONCLUSIONS AND CLINICAL RELEVANCE: The CO2 laser technique may have utility in the assessment of thermal nociceptive thresholds in pain-free cats after analgesic administration and may provide a simpler alternative to existing systems. Further exploration is required to examine its sensitivity and comparative utility.

Intra-articular injection of dexketoprofen in rat knee joint: histopathologic assessment of cartilage & synovium.

BACKGROUND & OBJECTIVES: Effective pain control following outpatient surgical procedures is an important aspect of patient discharge. This study was carried out with an aim to investigate the histopathological effects of intra-articular dexketoprofen trometamol injection in knee joint on synovium and cartilage in an experimental rat model. METHODS: In each of 40 rats, the right knee was designated as the study group and the left knee as the control group (NS group). Under aseptic conditions, 35 rats received an injection of 0.25 ml (6.25 mg) dexketoprofen trometamol into the right knee joint and an injection of 0.25 ml 0.9 per cent normal saline solution into the left knee joint. On the 1st, 2nd, 7th, 14th, and 21st days after intra-articular injection, rats in specified groups were sacrificed by intraperitoneal injection of 120 mg/kg sodium thiopental. Knee joints were separated and sectioned for histopathological examination. Inflammatory changes in the joints were recorded according to a grade scale. RESULTS: No significant difference in terms of pathological changes both in synovium and cartilage was observed between the NS group and the study group on days 1, 2, 7, 14 and 21 after intra-articular injection of dexketoprofen or saline in the knee joint. INTERPRETATION & CONCLUSIONS: The findings showed no evidence of significant histopathological damage to the cartilage and synovia for a period up to 21 days following intra-articular administration of dexketoprofen trometamol in the knee joints of rats.

Subcutaneous administration of ketoprofen delays Ehrlich solid tumor growth in mice / Administração subcutânea de cetoprofeno reduz o crescimento do tumor sólido de Ehrlich em camundongos

Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID) has proven to exert anti-inflammatory, anti-proliferative and anti-angiogenic activities in both neoplastic and non-neoplastic conditions. We investigated the effects of this compound on tumor development in Swiss mice previously inoculated with Ehrlich tumor cells. To carry out this study the solid tumor was obtained from cells of the ascites fluid of Ehrlich tumor re-suspended in physiological saline to give 2.5x106 cells in 0.05mL. After tumor inoculation, the animals were separated into two groups (n = 10). The animals treated with ketoprofen 0.1µg/100µL/animal were injected intraperitoneally at intervals of 24h for 10 consecutive days. Animals from the control group received saline. At the end of the experiment the mice were killed and the tumor removed. We analyzed tumor growth, histomorphological and immunohistochemical characteristics for CDC47 (cellular proliferation marker) and for CD31 (blood vessel marker). Animals treated with the ketoprofen 0.1µg/100µL/animal showed lower tumor growth. The treatment did not significantly influence the size of the areas of cancer, inflammation, necrosis and hemorrhage. Moreover, lower rates of tumor cell proliferation were observed in animals treated with ketoprofen compared with the untreated control group. The participation of ketoprofen in controlling tumor malignant cell proliferation would open prospects for its use in clinical and antineoplasic therapy...

O cetoprofeno é uma droga anti-inflamatória não esteroidal (NSAID), que exerce efeito anti-inflamatório, antiproliferativo e antitumoral em condições neoplásicas e não neoplásicas. Foram investigados os efeitos desse composto sobre o desenvolvimento tumoral de camundongos Swiss previamente inoculados com células do tumor de Ehrlich. Para realização deste estudo, o tumor sólido foi obtido a partir de células do fluido ascítico do tumor de Ehrlich suspendido em solução salina fisiológica para se obter 2,5x106 de células em 0,05mL. Após a inoculação do tumor, os animais foram separados em dois grupos (n = 10). Os animais do grupo tratado receberam cetoprofeno 0,1μg/100μL/animal por via intraperitoneal, em intervalos de 24 horas durante 10 dias consecutivos, e o controle 100µL de solução salina. No final do experimento, os animais foram sacrificados, e o tumor removido. Foram analisados o crescimento do tumor e as características histomorfológicas e imunoistoquímicas para CDC47 (marcador de proliferação celular) e para CD31 (marcador de vasos sanguíneos). Os animais tratados com o cetoprofeno 0,1μg/100μL/animal apresentaram menor crescimento do tumor. O tratamento não influenciou significativamente o tamanho das áreas de neoplasia, inflamação, necrose e hemorragia. Em contraste, uma menor taxa de proliferação das células neoplásicas foi observada nos animais tratados com cetoprofeno em comparação com o grupo controle. A participação do cetoprofeno em controlar a proliferação de células neoplásicas abre perspectivas para sua utilização em terapia clínica antineoplásica...

Magnetic resonance microscopy for assessment of morphological changes in hydrating hydroxypropylmethylcellulose matrix tablets in situ-is it possible to detect phenomena related to drug dissolution within the hydrated matrices?

PURPOSE: So far, the hydrated part of the HPMC matrix has commonly been denoted as a "gel" or "pseudogel" layer. No MRI-based results have been published regarding observation of internal phenomena related to drug dissolution inside swelling polymeric matrices during hydration. The purpose of the study was to detect such phenomena. METHODS: Multiparametric, spatially and temporally resolved T2 MR relaxometry, in situ, was applied to study formation of the hydration progress in HPMC matrix tablets loaded with L-dopa and ketoprofen using a 11.7 T MRI system. Two spin-echo based pulse sequences were used, one of them specifically designed to study short T2 signals. RESULTS: Two components in the T2 decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T2 values, were obtained. Based on the data, different region formation patterns (i.e. multilayer structure) were registered depending on drug presence and solubility. Inside the matrix with incorporated sparingly soluble drug a specific layer formation due to drug dissolution was detected, whereas a matrix with very slightly soluble drug does not form distinct external "gel-like" layer. CONCLUSIONS: We have introduced a new paradigm in the characterization of hydrating matrices using (1)H MRI methods. It reflects molecular mobility and concentration of water inside the hydrated matrix. For the first time, drug dissolution related phenomena, i.e. particular front and region formation, were observed by MRI methods.

Comparative assessment of effectiveness of ketoprofen and ketoprofen/beta-cyclodextrin complex in two experimental models of inflammation in rats.

Oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) can lead to adverse effects such as gastrointestinal distress. The complexation of different groups of active substances with ß-cyclodextrin (ß-CD) has drawn considerable interest over recent years. The purpose of this study was to analyze the ketoprofen/ß-cyclodextrin (K/ß-CD) conjugate complex as well as to assess its anti-inflammatory effect after oral administration (doses of 30 mg/m(2) and 15 mg/m(2) of body surface), compared with ketoprofen. The studies were done on two models of experimentally-induced acute inflammation in rats (n = 48, 6/group), by means of intraplantar administration of a 10% aqueous kaolin suspension and intraperitoneal administration of a 1% sodium thioglycolate solution. The dynamics of the acute inflammatory process and the anti-inflammatory effects were monitored using plethysmometric determinations after 3, 6, 9, 12, 24 and 48 h (plantar inflammation), and the absorbance of the exudates (spectrophotometrically read) and nucleated cell counts after 24 h (peritoneal inflammation). The coupling of ketoprofen with ß-CD resulted in increased solubility (100% in 60 min) of the newly-formed product, which further resulted in a higher bioavailability compared with ketoprofen (<40% in 120 min). In both models of experimentally-induced inflammation, the K/ß-CD complex had a higher anti-inflammatory activity than ketoprofen.

[Assessment of practices in postoperative analgesia in caesarean before and after implementation of an information program]. / Évaluation des pratiques de prise en charge analgésique en postopératoire de césarienne avant et après mesures d'amélioration.

OBJECTIVE: To assess the improvement of practices in postoperative analgesia after a cesarean section post implementation of a corrective program. STUDY DESIGN: Prospective impact study. PATIENTS AND METHODS: After obtaining ethics approval, we included all patients undergoing a cesarean section at Montpellier University Hospital during February 2011 (PRE group) and March 2012 (POST group). The patients were interviewed on the fourth day postpartum about pain management and related data was collected from the chart. From March 2011 to February 2012, training sessions were held for the paramedical and medical teams. RESULTS: Sixty patients were included in each group. The two groups were not significantly different. The mean overall numeric rating scale worst pain score between Day 0 and Day 4 in POST group was lower (5.5±2.5 vs. 6.5±2.4 p<0.01) and impairment during mobilization decreased significantly. Compliance with protocols improved in the POST group: the number of women receiving full analgesia regiment increased from 12% to 68% between PRE and POST period. CONCLUSION: After an awareness campaign of the paramedical and medical staff, we succeeded in improving significantly the routine use of analgesics regardless of their level. Nevertheless healthcare professionals still seem reluctant to administer opioids.

Avaliação da eficácia da analgesia preemptiva na cirurgia de extração de terceiros molares inclusos / Assessment of preemptive analgesia efficacy in surgical extraction of third molars / Evaluación de la eficácia de la analgesia de prevención en la cirugía de extracción de terceros molares incluidos

JUSTIFICATIVA E OBJETIVOS: A literatura sobre analgesia preemptiva é controversa. A confiabilidade dos resultados e a dificuldade de reprodutibilidade das pesquisas contribuem para a não elucidação do tema. O objetivo desse estudo é testar a eficácia da administração preemptiva de Cetoprofeno 150 mg via oral dois dias antes da cirurgia de extração deterceiros molares, comparando no mesmo paciente com a administração pós-operatória. MÉTODO: Treze pacientes foram submetidos à cirurgia de extração bilateral de terceiros molares inferiores inclusos em dois procedimentos distintos. De forma randomizada e duplo cega, em um procedimento foi administrado Cetoprofeno 150 mg via oral a cada 12 horas dois dias antes da cirurgia e, após o procedimento, continuou-se o mesmo medicamento por mais três dias. De outro lado, foi utilizado um controle (placebo) via oral a cada 12 horas dois dias antes da cirurgia e, após o procedimento, continuou-se o Cetoprofeno 150 mg a cada 12 horas por mais três dias. A dor pós-operatória foi avaliada por meio da escala visual analógica, da escala nominal e da quantidade de consumo de analgésicos de resgate. RESULTADOS: Não foi observada diferença estatisticamente significante na dor pós-operatória entre o tratamento preemptivo e o controle. CONCLUSÃO: Neste modelo experimental, a analgesia preemptiva não se mostrou eficaz na redução da dor pós-operatória na cirurgia de extração de terceiros molares inclusos em comparação com a administração pós-operatória do mesmo medicamento.

BACKGROUND AND OBJECTIVES: Literature on preemptive analgesia is controversial. Reliability of results and difficult reproducibility of research contribute for non-elucidation of the subject. The aim of this study is to test the efficacy of oral ketoprofen (150 mg) preemptively administrated two days before third molar surgery, compared with postoperative administration in the same patient. METHODS: Thirteen patients underwent surgical removal of bilateral third molar in two separate procedures. In a random and double blind procedure, oral ketoprofen 150 mg was administered every 12 hours two days before surgery and, after the procedure, the same drug was administered for three days. On the other side, a control (placebo) was used orally every 12 hours two days before surgery and, after the procedure, ketoprofen 150 mg was administered every 12 hours for three days. Postoperative pain was assessed by visual analogue scale, nominal scale, and amount of rescue analgesics consumed. RESULTS: There was no statistically significant difference in postoperative pain between the preemptive treatment and control. CONCLUSION: In this experimental model, preemptive analgesia was not effective in reducing postoperative pain in surgical extraction of third molar compared with the postoperative administration of the same drug.

JUSTIFICATIVA Y OBJETIVOS: La literatura sobre la analgesia de prevención es controversial. La confiabilidad de los resultados y la dificultad de reproductibilidad de las investigaciones contribuyen para que el tema no quede clarificado en su totalidad. El objetivo de este estudio, es comprobar la eficacia de la administración de prevención del Cetoprofeno 150 mg por vía oral dos días antes de la cirugía de terceros molares, comparando al mismo paciente con la administración postoperatoria. MÉTODO: Trece pacientes se sometieron a la cirugía de extracción bilateral de terceros molares inferiores incluidos en dos procedimientos distintos. De forma randomizada y doble ciega, en un procedimiento se administró Cetoprofeno 150 mg por vía oral a cada 12 horas dos días antes de la cirugía y después del procedimiento continuamos con el mismo medicamento por tres días más. Por otra parte, fue utilizado un control (placebo) vía oral a cada 12 horas dos días antes de la cirugía y después del procedimiento se continuó con el Cetoprofeno 150 mg a cada 12 horas por tres días más. El dolor del postoperatorio, se evaluó por medio de la escala visual analógica, de la escala nominal y de la cantidad de consumo de analgésicos de rescate. RESULTADOS: No se observaron diferencias estadísticamente significativas en el dolor postoperatorio entre el tratamiento de prevención y el control. CONCLUSIONES: En este modelo experimental, la analgesia de prevención no fue eficaz en la redución del dolor postoperatorio en la cirugía de extracción de terceros molares incluidos en comparación con la administración postoperatoria del mismo medicamento.

Modified coaxial electrospinning for the preparation of high-quality ketoprofen-loaded cellulose acetate nanofibers.

This study investigates the use of a modified coaxial electrospinning process in the production of drug-loaded cellulose acetate (CA) nanofibers. With CA employed as a filament-forming matrix and ketoprofen (KET) as an active pharmaceutical ingredient, modified coaxial processes using sheath fluids comprising only mixed solvents were undertaken. With a sheath-to-core flow rate ratio of 0.2:1, the nanofibers prepared from the coaxial process had a smaller average diameter, narrower size distribution, more uniform structures, and smoother surface morphologies than those generated from single fluid electrospinning. In addition, the coaxial fibers provided a better zero-order drug release profile. The use of a sheath solvent means that the core jet is subjected to electrical drawing for a longer period, facilitating homogeneous core jet solidification and retarding the formation of wrinkles on the surface of the nanofibers. This modified coaxial electrospinning protocol allows the systematic fabrication of functional polymer nanofibers with improved quality.

An initial safety assessment of hepatotoxic and nephrotoxic potential of intramuscular ketoprofen at single repetitive dose level in broiler chickens.

A study was undertaken to assess the hepatotoxic and nephrotoxic potential of ketoprofen in comparison with diclofenac upon short-term intramuscular (i.m.) administration in broiler chickens. Eighteen broiler chickens were randomly divided into 3 groups of 6 birds each. Group I served as the control and received normal saline (0.1 mL, i.m.), group II was the positive control and received diclofenac sodium (2.5 mg/kg, i.m.), and group III received ketoprofen (3 mg/kg, i.m.) daily at 24-h intervals for 5 consecutive days. Diclofenac sodium-treated birds showed severe clinical signs of toxicity with high mortality, a significant increase (P < 0.01) in serum concentrations of creatinine, uric acid, alanine aminotransferase, and aspartate aminotransferase, and these changes correlated well with gross and microscopic examination findings of kidney and liver. In contrast, ketoprofen-treated birds did not show any adverse clinical signs and no significant increase in concentration of creatinine, uric acid, alanine aminotransferase, and aspartate aminotransferase when compared with birds in group I. Gross and microscopic examination of kidney and liver showed normal organ architecture. Thus, based on the present findings, it was concluded that ketoprofen at the dose of 3 mg/kg administered intramuscularly daily for 5 d was nontoxic to broiler chickens.

Microdialysis assessment of percutaneous penetration of ketoprofen after transdermal administration to hairless rats and domestic pigs.

The study was performed to evaluate the percutaneous penetration of ketoprofen after transdermal administration using a microdialysis technique in pigs, in comparison with rats. Ketoprofen release from patches was determined by analysis of the remaining drug content after application to hairless rats and pigs. Skin and knee joint penetration of ketoprofen was tested by microdialysis, and recovery was determined by retrodialysis. Residual rates in hairless rats and pigs were 68.1 ± 1.6% and 81.7 ± 4.4%, respectively, at 10h. The average recoveries of ketoprofen over 480 min in the skin and knee joint cases were 72.0 ± 3.4% and 9.8 ± 6.2% in rats and 72.3 ± 2.5% and 57.6 ± 3.1% in pigs, respectively. In rats, ketoprofen was rapidly absorbed with transdermal administration, with C(max) values of 191.7 ± 76.2 and 35.5 ± 21.7 ng/mL and AUC(0-8h) values of 918.2 ± 577.5 and 195.9 ± 137.1 ngh/mL, respectively, for the skin and knee joint. The C(max) values for the pig were 20.9 ± 18.5 and 3.7 ± 3.0 ng/mL, with AUC(0-8h) values of 73.1 ± 69.2 and 16.1 ± 16.1 ngh/mL. Ketoprofen concentrations within skin and knee joint of non-application sites in rats and pigs were less than 0.8 ng/mL. Transdermal administration of ketoprofen significantly reduced prostaglandin E2 levels in the skin of the application site and showed a tendency for inhibition in the knee joint. We thus demonstrated that topical patches containing ketoprofen can deliver the drug through the skin and knee joint of pigs and rats via direct diffusion, and microdialysis data with the pig may be useful for the prediction of human tissue penetration of drugs with transdermal administration.

Cutaneous adverse effects of ketoprofen for topical use: clinical patterns and costs.

BACKGROUND: Since its introduction in France, ketoprofen for topical use has been associated with a large number of cutaneous adverse effect reports. Therefore, the French Medicine Agency progressively introduced warnings and contraindications to its use. Despite this, serious adverse drug reactions (ADRs) still occur. OBJECTIVE: To describe clinical patterns and estimate costs of spontaneously reported cutaneous ADRs of topical ketoprofen. METHODS: All cases of cutaneous ADRs of topical ketoprofen reported to the Bordeaux regional pharmacovigilance center between January 1989 and December 2006 were included. Clinical patterns, in respect of adherence to recommendations, causality, seriousness, and direct costs incurred by the ADRs, were assessed. RESULTS: A total of 136 cases were reported (median age: 42 years, 55.9% women). Proper use of topical ketoprofen regarding indications, warnings, and contraindications was not respected by one-third of the patients. Almost all cases occurred during sunny months. Symptoms consisted predominantly of bullous eruptions (29.4%) or contact dermatitis (27.2%). Generalized lesions were observed in 37.5% of patients. Causality was considered at least possible for most of the cases (92.6%). These ADRs induced hospital admission in 15 cases (11.0%). The total estimated cost was euro 42,962 ($US 66,559), corresponding to euro 316 per case. This mean cost was nine times higher for serious ADRs. CONCLUSION: Topical ketoprofen is used to treat benign symptoms but can be associated with serious and costly cutaneous ADRs. Furthermore, the number of cases and the calculated costs may have been greatly under-estimated in the present study.

A randomized, controlled clinical trial of ketoprofen for sickle-cell disease vaso-occlusive crises in adults.

Vaso-occlusive crisis (VOC) is the primary cause of hospitalization of patients with sickle-cell disease. Treatment mainly consists of intravenous morphine, which has many dose-related side effects. Nonsteroidal antiinflammatory drugs have been proposed to provide pain relief and decrease the need for opioids. Nevertheless, only a few underpowered trials of nonsteroidal antiinflammatory drugs for sickle-cell VOC have been conducted, and conflicting results were reported. We conducted a phase 3, double-blind, randomized, placebo-controlled trial with ketoprofen (300 mg/day for 5 days), a nonselective cyclooxygenase inhibitor, for severe VOC in adults. A total of 66 VOC episodes were included. The primary efficacy outcome was VOC duration. The secondary end points were morphine consumption, pain relief, and treatment failure. Seven VOC episodes in each group were excluded from the analysis because of treatment failures. No significant between-group differences were observed for the primary outcome or the secondary end points. Thus, although ketoprofen was well-tolerated, it had no significant efficacy as treatment of VOC requiring hospitalization. These findings argue against its systematic use in this setting.

[Assessment of quality in day-case hand surgery]. / Démarche d'assurance qualité en chirurgie ambulatoire de la main.

OBJECTIVE: To determine the level of satisfaction in terms of pain relief and comfort among patients receiving different postoperative analgesia protocols after hand surgery under regional anaesthesia in a day care unit. METHODS: Cohort study among patients after hand surgery under regional anaesthesia during two consecutive three months time periods, with patient stratification according to the expected pain level with different balanced analgesia protocols (group A: carpal tunnel, group B: other surgery without bone involvement, group C: bone surgery). A telephone survey, scoring analgesia and comfort, each with a numerical (0-10) scale was conducted on days 1 and 7. During the first period analgesia for groups A and B was the same (acetaminophen-dextropropoxyphene or acetaminophen-codeine) and group C patients were treated with acetaminophen-ketoprofen-tramadol. In the second period analgesia was reduced for group A (acetaminophen alone) and increased for group B (acetaminophen-ketoprofen-tramadol) and group C (duration increased from 3 to 7 days). RESULTS: For carpal tunnel surgery, analgesia with acetaminophen alone was efficient, (Pain scale [PS] d0=2[0-10], PS d1=1 [0-10] and PS d2-d4=0,5 [0-10]). This surgery does not elicit important pain, there is no benefit in adding other analgesics. For group B, a significant improvement in postoperative pain was observed (postoperative d1 p<0.03) with a major increase in side effects (2/57 vs 17/48 p<0.001). For group C, therapeutic changes were ineffective (PS d0=2 vs 3.5 et PS d1=3 vs 5 [NS]) and we noticed an increase in side effects (p<0.05). One third of all patients are totally satisfied on day 7, logistic regression showing the role of inefficient analgesia in late postoperative period (PS>2 between d2-d4). Between day 1 and day 7, 20% of the patients change their point of view, those who feel less satisfied on day 7 complained of a more severe postoperative pain between day 2 and 4 (p<0.001) and between day 5-7 (p<0.01). CONCLUSION: For hand surgery on day case, quality of late postoperative analgesia (day 2-day 7) is strongly related to patient's satisfaction on day 7.

[Questionnaire survey of patients comparing the usability of brand-name and generic ketoprofen tapes].

Since patients who used brand-name and generic ketoprofen (KP) tapes dispensed in the Fukuoka City Pharmaceutical Association Pharmacy complained of a difference in feeling between the two products, we conducted a questionnaire survey in patients using KP tapes to determine the usability of brand-name and generic tapes. Patients receiving the brand-name KP tape (product A) and/or a generic KP tape (product B) in our pharmacy were interviewed concerning 20 items including 1) dosage regimen, 2) outer package, 3) liner, 4) the tape itself, and 5) condition of application sites. A significant difference in usability between products A and B was observed in 4 of the 20 items evaluated, i.e., 1) easiness of opening of the outer pouch, 2) easiness of removing the liner film, 3) condition of the application site after removal of the tape, and 4) relief of pain in the target lesion after application. As suggested by patients who had complained of a difference in usability between products A and B, the participants in the survey tended to prefer the brand-name KP tape to the generic product. The findings of the survey indicate that when a brand-name product is switched to generic products, pharmacists should evaluate the usability of such products carefully to select those that will ensure proper drug use by patients.

Ex vivo mucoadhesion and in vivo bioavailability assessment and correlation of ketoprofen tablet dosage forms containing bioadhesives.

The purposes of this study were to assess the mucoadhesion and bioavailability and their correlation for ketoprofen tablet dosage forms (F1-F6) containing polycarbophil (PC), sodium carboxymethylcellulose (Na CMC) as bioadhesives, Avicel pH 101 as direct compressible tablet vehicle or mixtures of these, and non compressible vehicles such as lactose and starch. For mucoadhesion assessment, we used sheep gastric mucosa and for bioavailability we used six human volunteers in an open randomized seven-way crossover study. Young's modulus (YM) and relative bioavailability (RB) parameters were used for evaluation of mucoadhesion and bioavailability, respectively. The results indicated that F2 containing Na CMC (72.5%) showed the highest value of YM (7.6 +/- 0.76 pascals) and 119.4 +/- 3.2% for RB. Decreasing the amount of Na CMC to 10% in F3 and F6 decreased the values of YM and RB to 1.4 +/- 0.08 and 84 +/- 2.05 in F3, 4.6 +/- 0.43 and 114.7 +/- 2.46 in F6, respectively. The highest RB (152.3 +/- 2.56) was observed in F5 containing starch and Avicel pH 101. This formulation showed 6 +/- 0.87 for YM. F4 containing PC (10%) showed 5.1 +/- 0.43 and 74.15 +/- 1.98 for YM and RB respectively. The lowest value of YM was observed in F1 containing Avicel pH 101 (0.27 +/- 0.01) which also showed low RB (93.3 +/- 2.3). In conclusion, formulations containing bioadhesives and/or starch in high concentration showed high values of YM and RB which indicate good correlation between mucoadhesion and bioavailability. Bioadhesives may show a high potential to improve bioavailability and therapeutic efficacy of ketoprofen in tablet dosage forms.

Efficacy of oral rofecoxib versus intravenous ketoprofen as an adjuvant to PCA morphine after urologic surgery.

BACKGROUND: Adjunctive use of nonsteroidal anti-inflammatory drugs has become increasingly popular in the perioperative period because of their opioid-sparing effects. This randomized, controlled, double-dummy study was designed to evaluate the cost-effectiveness of using oral rofecoxib as an alternative to intravenous ketoprofen for pain management in patients undergoing urologic surgery. METHODS: Seventy patients were randomly assigned to receive either a placebo (Control) or rofecoxib 50 mg po (Rofecoxib) 1 h prior to surgery. After a standardized spinal anesthetic, patients in the Control group received ketoprofen 100 mg IV q 8 h for 24 h, while the Rofecoxib group received an equivolume of saline at 8-h intervals for 24 h. Both groups were allowed to self-administer morphine (1 mg IV boluses) using a PCA delivery system. The need for 'rescue' analgesic medication, as well as pain scores [using an 11-point verbal rating scale (VRS) (0 = none to 10-severe)], were recorded at 1, 2, 6, 12, and 24-h intervals after surgery. In addition, the incidences of side-effects were recorded at the end of the study period. RESULTS: Total amount of morphine required in the initial 24-h postoperative period was nonsignificantly reduced in the Rofecoxib group (29 +/- 2 vs. 37 +/- 4 mg). More importantly, the percentage of patients reporting moderate-to-severe pain (VRS score > or =4) during the study period was lower in the Rofecoxib group (12 vs. 22%, P < 0.05). The daily cost of rofecoxib (USD 1.14 for 50-mg dose) was also significantly less than ketoprofen (USD 3.06 for three 100-mg doses). CONCLUSION: Premedication with oral rofecoxib (50 mg) is a cost-effective alternative to the parenteral nonselective NSAID, ketoprofen (100 mg q 8 h), when used as an adjuvant to PCA morphine for pain management after urologic surgery.

[Gastric endoscopic assessment after treatment with orally administered ketoprofen lysine salt (80 mg granular sachet). Controlled study vs placebo]. / Valutazione endoscopica gastrica dopo trattamento con ketoprofene sale di lisina 80 mg granulato in bustine per uso orale. Studio controllato vs placebo.

In this study, a new oral granular formulation of ketoprofen lysine salt, a non steroidal antiinflammatory drug (NSAID) derived from propionic acid, and placebo, were compared for their local effect on the gastric mucosa of healthy, human volunteers. The study was carried out with a double-blind, randomized, parallel-group, design. 10 healthy volunteers were administered one sachet containing 80 mg of ketoprofen lysine salt and 10 volunteers with placebo. The subjects were gastroscoped at baseline and following 10 days drug administration; tolerability was assessed by analysis of the hematology and biochemistry laboratory results, the adverse reaction reports and by the Investigator's and subject's global assessment at the final visit. No symptoms of gastric intolerance were referred in both groups. No statistically significant differences were found between treatments in laboratory results and in final post-treatment tolerability evaluation (Mann-Whitney's test U, Phi and Cramer tests).