萘普生和双氯芬酸止痛作用比较的随机对照试验

萘普生2mL(0.2g)或双氯芬酸2mL(50mg)肌注于类风湿关节炎170例,bid,共14d,qd或bid于痛经女性70例及手术后疼痛72例作随机双盲试验。结果2药间止痛作用无显著差别(P>0.05)。在肌注处较强疼痛其萘普生组和双氯芬酸组分别为43％和42％。     

右旋酮洛芬和酮洛芬治疗感冒的疗效比较

目的:评价右旋酮洛芬肠溶片治疗感冒的疗效和安全性.方法:感冒患者41例,随机分为治疗组20例和对照组21例,治疗组口服右旋酮洛芬肠溶片25 mg,tid;对照组口服酮洛芬片50 mg,tid,疗程均为3 d.比较解热镇痛疗效和不良反应.结果:两组有效率分别为90.0%和85.0%,不良反应发生率分别为10.0%和20.0%,两组比较差异无显著性(P＞0.05).结论:右旋酮洛芬治疗感冒的疗效较高,安全性较好.     

透皮酮洛芬可减轻膝OA疼痛

据一项在欧洲进行的多中心III期研究的结果,IDEAAG公司的酮洛芬透皮剂(ketoprofen,Idea-033)(I)可以有效地减轻膝骨关节炎(OA)病人的疼痛。     

外用双氯芬酸钾凝胶治疗局部风湿性疼痛综合征

目的 比较研究双氯芬酸钾凝胶（ＤＰＧ）和双氯芬酸钠凝胶（ＤＳＧ）治疗局部风湿性疼痛综合征的疗效和安全性。方法 试验设计为多中心、随机对照、单盲、平行性的比较研究。试验组 ６０例,１％ＤＰＧ外用,每日３－４次,每次２－４ｇ,日总量不超过２０ｇ,疗程２周;对照组４５例,１％ＤＳＧ外用,使用方法同ＤＰＧ。结果 ２周时ＤＰＧ的总有效率为 ８８％,ＤＳＧ总有效率为８７％,ＤＰＧ组疗效明显高于 ＤＳＧ组（Ｐ＜０．０５）。两药均能显著改善病人的临床症状和体征（Ｐ＜０．０５～０．００１）,两组相比ＤＰＧ对关节肿胀数的改善优于ＤＳＧ组（Ｐ＜０．０５）,对其他各指标的改善两组间差异无显著性（Ｐ＞０．０５）． ＤＰＧ的耐受性良好,无１例病人发生不良反应;ＤＳＧ组的不良反应发生率为２％,两组间差异无显著性（Ｐ＞０．０５）．结论ＤＰＧ治疗局部风湿性疼痛综合征的疗效优于ＤＳＧ,且耐受性好,无明显不良反应。     

酮洛芬治疗痛经的药效学研究

酮洛芬对于催产素引起的大白鼠离体子宫和家兔在体子宫收缩均有明显的抑制作用，其小白鼠的ＬＤ５０测定值为４１１·６２ｍｇ／ｋｇ，提示酮洛芬用于痛经的治疗是有效的。     

双氯芬酸二乙胺乳胶剂和双氯芬酸钠肠溶片治疗肌筋膜疼痛综合征的疗效比较

目的比较双氯芬酸二乙胺乳胶剂和双氯芬酸钠肠溶片治疗肌筋膜疼痛综合征的临床疗效。方法选择肌筋膜疼痛综合征患者80例,随机分为双氯芬酸二乙胺乳胶剂治疗组(外用组)和双氯芬酸钠肠溶片口服治疗组(口服组)。所有患者治疗前及治疗后1周、2周、3周分别进行VAS评分,并记录药物的不良反应。结果各组治疗前后的VAS评分组内比较差异有统计学意义(P<0.01),组间比较无明显差异(P>0.05);外用组不良反应少且轻微,明显低于口服组(P<0.01)。结论双氯芬酸外用乳胶剂治疗肌筋膜疼痛综合征疗效好,不良反应小。     

04048 透皮酮洛芬可减轻膝OA疼痛

据一项在欧洲进行的多中心Ⅲ期研究的结果，IDEAAG公司的酮洛芬透皮剂（ketoprofen，Idea-033）（Ⅰ）可以有效地减轻膝骨关节炎（OA）病人的疼痛。     

Clinical and methodological studies on intramuscular ketoprofen in postoperative rheumatic pain

Summary Ketoprofen (Kp), given intramuscularly to 15 patients with chronic arthritis on the day after elective joint surgery (13), or during bouts of extreme pain (2), resulted in satisfactory pain relief, and seemed able to replace opiates. A new assay method for plasma Kp, based on gas chromatography/high resolution mass fragmentography is described, which permits determination of Kp even in the presence of probenecid. Kp was rapidly absorbed and peak plasma levels of 10.2 to 18.6 mol/l were attained within 30 min. Probenecid did not interfere with the elimination of Kp.     

The efficacy of ketoprofen and paracetamol (acetaminophen) in postoperative pain after third molar surgery

1 A placebo-controlled, double-blind, randomized trial was carried out to evaluate the efficacy of single doses of racemic ketoprofen 12.5 and 25  mg and paracetamol 500 and 1000  mg in patients with post-operative pain after third molar surgery over a 6  h investigation period.
2 Outcome variables included overall pain scores (AUC(0,360  min), maximum pain relief, pain relief at 1  h after dosage and the number of patients taking escape analgesics.
3 Overall pain scores (AUC(0,360  min) were significantly lower for all active treatments when compared to placebo ( P <0.01).
4 Both ketoprofen treatments and patients treated with paracetamol 1000  mg reported significantly greater pain relief ( P <0.01) and a later time to taking escape analgesics ( P <0.01) than patients medicated with placebo.
5 At 1  h after dosage, pain scores were significantly less ( P <0.01) after both doses of ketoprofen when compared with placebo.
6 Single doses of ketoprofen 12.5 and 25  mg, together with paracetamol 1000  mg are effective analgesics for treating post-operative pain after third molar surgery. These treatments provide up to 4  h of pain relief after this surgical procedure.     

Effective postoperative pain control by preoperative injection of diclofenac

Summary We have treated ninety-five patients undergoing surgical removal of third molar with diclofenac or placebo, administered double-blind either pre- or postoperatively. Postoperative pain was recorded hourly for the first 8 h using a 100 mm visual analogue scale.Preoperative administration of diclofenac produced more effective pain relief than either postoperative administration or placebo.Since diclofenac has an inhibitory action on prostaglandin synthesis prophylactic intramuscular administration may have reduced the inflammatory process before synthesis of prostaglandins was activated.     

A diclofenac suppository–nabumetone combination therapy for arthritic pain relief and a monitoring method for the diclofenac binding capacity of HSA site II in rheumatoid arthritis

Diclofenac suppository, a non‐steroidal anti‐inflammatory drug (NSAID), is used widely in rheumatoid arthritis (RA) patients with severe arthritic pain. As the binding percentage of diclofenac to serum proteins is high, its free (unbound) concentration after rectal administration is low. To increase temporarily the free concentration of diclofenac and to enhance its analgesic effect by inhibiting the protein binding of diclofenac, the analgesic effect of diclofenac was examined before and after the start of an inhibitor administration to RA patients with insufficient control of arthritic pain, and the protein binding capacity of diclofenac was evaluated. Binding experiments were performed by ultrafiltration, and arthritic pain was recorded by the face scale. Free fractions of diazepam and diclofenac were augmented by increasing 6‐methoxy‐2‐naphthylacetic acid (6‐MNA; the active metabolite of the NSAID nabumetone) concentrations. The free fraction of diazepam increased after the start of nabumetone administration to RA patients, and arthritic pain relief was observed. These results suggest that 6‐MNA has an inhibitory effect on the protein binding of diclofenac and the free fraction of diazepam can be used to evaluate the binding capacity of diclofenac. It is considered that diclofenac suppository–nabumetone combination therapy and the method for protein binding monitoring by diazepam can positively benefit RA patients with insufficient control of arthritic pain. Copyright © 2013 John Wiley & Sons, Ltd.     

Comparative bioavailability of diclofenac hydroxyethylpyrrolidine vs diclofenac sodium in man

Summary A pharmacokinetic study in man has been made of a new dosage form of diclofenac hydroxyethylpyrrolidine (DIEP); soluble salt packed in sachets was compared with diclofenac sodium as enteric coated tablets.Oral DIEP 2×50 mg showed a significant difference in absorption kinetics (ka, lag time and t_max) as compared to oral diclofenac sodium 2×50 mg. A relevant plasma concentration of diclofenac was detected just 15 min after DIEP, while diclofenac sodium produced a measurable plasma concentration only 0.5–1 h after the treatment. C_max and t_1/2 after DIEP and diclofenac sodium were comparable. Comparison of the two AUC values showed that DIEP was bioequivalent to diclofenac sodium (Q=100%).     

氟比洛芬酯脂微球载体制剂与注射用酮洛芬对照治疗术后及癌性疼痛

目的:观察氟比洛芬酯与酮洛芬对照治疗术后及癌性疼痛患者的有效性.方法:日本36家医院共入选腹部术后患者224例,癌性疼痛患者163例,随机分为氟比洛芬酯组192例与酮洛芬组195例,分别用氟比洛芬酯与酮洛芬安慰剂和酮洛芬与氟比洛芬酯安慰剂.氟比洛芬酯及其安慰剂5mL静脉内注射,酮洛芬及其安慰剂每瓶用2.5mL溶液溶解臀部肌内注射.结果:可评价病例氟比洛芬酯组对术后疼痛111例患者改善率为73.9%,高于酮洛芬组(n=109)的66.1%,但2组差异无显著性(P>0.05);药效持续时间氟比洛芬酯组比酮洛芬组延长(P<0.05).氟比洛芬酯组癌性疼痛(n=77)改善率为77%,高于酮洛芬组(n=81)的59.3% (P>0.05),药效持续时间氟比洛芬酯组比酮洛芬组延长(P<0.05).结论:在治疗术后疼痛和癌性疼痛时,氟比洛芬酯的疗效与酮洛芬相近,但镇痛时间明显延长.     

Population pharmacokinetics of oral diclofenac for acute pain in children

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Diclofenac is an effective oral analgesic for acute postoperative pain. In adults 25 mg is half as effective as 50 mg, but 50 mg and 100 mg are similarly effective (ceiling effect). Diclofenac has linear pharmacokinetics in this range.
• Diclofenac is frequently used ‘off-label’ in children for acute pain but optimum dosing is unclear (dosing of diclofenac in clinical paediatric studies ranges from 0.5–2.5 mg kg⁻¹). There is currently no licensed oral paediatric formulation of diclofenac.

WHAT THIS STUDY ADDS

• Using a new diclofenac oral suspension, a dose of 1 mg kg⁻¹ in children aged 1 to 12 years gives a similar exposure to 50 mg in adults; paediatric patients are unlikely to benefit from higher doses.

AIMS

To develop a population pharmacokinetic model for a new diclofenac suspension (50 mg 5 ml⁻¹) in adult volunteers and paediatric patients, and recommend a dose for acute pain in children.

METHODS

Blood samples were drawn at the start and end of surgery, and on removal of the venous cannula from 70 children (aged 1 to 12 years, weight 9 to 37 kg) who received a preoperative oral 1 mg kg⁻¹ dose; these were pooled with rich (14 post-dose samples) data from 30 adult volunteers. Population pharmacokinetic modelling was undertaken with NONMEM. The optimum adult dose of diclofenac for acute pain is 50 mg. Simulation from the final model was performed to predict a paediatric dose to achieve a similar AUC to 50 mg in adults.

RESULTS

A total of 558 serum diclofenac concentrations from 100 subjects was used in the pooled analysis. A single disposition compartment model with first order elimination and dual absorption compartments was used. The estimates of CL/F and V_D/F were 53.98 l h⁻¹ 70 kg⁻¹ and 4.84 l 70 kg⁻¹ respectively. Allometric size models appeared to predict adequately changes in CL and V_D with age. Of the simulated doses investigated, 1 mg kg⁻¹ gave paediatric AUC_{(0, 12 h)} to adult 50 mg AUC_{(0, 12 h)} ratios of 1.00, 1.08 and 1.18 for ages 1–3, 4–6 and 7–12 years respectively.

CONCLUSIONS

This study has shown 1 mg kg⁻¹ diclofenac to produce similar exposure in children aged 1 to 12 years as 50 mg in adults, and is acceptable for clinical practice; patients are unlikely to obtain further benefit from higher doses.     

Effects of diclofenac and dextropropoxyphene on experimental thermal pain in healthy subjects

Rundgren M, Kankaanranta H, Nurmikko T, Moilanen E. Effects of diclofenac and dextropropoxyphene on experimental thermal pain in healthy subjects. Inflammophannacology. 1997;5:l-7. In the present double-blind placebo-controlled study the effects of a single oral dose of 50 mg diclofenac or 65 mg dextropropoxyphene were determined on thermal thresholds in 84 healthy subjects. Perception thresholds for warm, cold, heat pain and cold pain as well as heat-pain tolerance were determined by the Marstock method before and 90 min after administration of the drug. No alterations in thermal thresholds were observed except a slight unexpected decrease in heat-pain perception threshold in the dextropropoxyphene group. The data confirms the reproducibility of the Marstock method and the lack of interference with some analgesics in the common use. The apparent lack of analgesic effect of two clinically effective analgesics, diclofenac and dextropropoxyphene, supports the assumption that these compounds have a poor analgesic action in physiological and neural pain. The data suggest that determination of drug effects on heat-pain thresholds in uninjured skin may underestimate clinical action of analgesic drugs and is therefore not sufficient for testing or demonstrating clinical efficacy of analgesic compounds.     

Controlled-release indomethacin and sustained-release diclofenac sodium in the treatment of rheumatoid arthritis: A comparative controlled clinical trial

Summary

The efficacy and tolerability of a new, controlled-release indomethacin (7.5?mg) tablet was compared to that of a sustained-release diclofenac sodium (100?mg) tablet in 84 patients with rheumatoid arthritis. The study was designed as a double-blind, double-dummy crossover trial, patients being allocated at random to receive 1 active tablet and 1 placebo tablet of the alternative medication at night for 4 weeks before being crossed over to the alternative treatment for a further 4 weeks. Patient and clinical assessments on entry and at the end of each treatment period showed that pain scores for day and night, duration of morning stiffness, requirement for escape analgesia (paracetamol) and treatment preference were similar for both treatments. Both preparations also significantly improved the degree of joint tenderness compared to baseline (p<0.001), as measured by a modified Ritchie Articular Index. Incidence and severity of side-effects were comparable, with a significant improvement in degree of constipation reported for both treatments compared to baseline (p<0.05). The incidence and severity of headache was statistically significantly worse (p<0.05) for controlled-release indomethacin; however, there was no difference in any other parameter of tolerability. It was concluded that controlled-release indomethacin tablets (75?mg) given as a single night-time dose were as efficacious and well tolerated as sustained-release diclofenac sodium (100mg).