Kinase modulators approved by FDA in 2022 / 药学学报

The FDA approved a total of 37 new drugs in 2022, including 22 new molecular entities and 15 new biological products. This is the year with the lowest number of new drugs approved by the FDA since 2017. Among these approved drugs, 21 new drugs belong to the "first-in-class" category, accounting for 56% of the total approved drugs, which is the highest ratio in the past 10 years. Among the drugs approved in 2022, there are 5 small molecule kinase modulators, including the tyrosine kinase 2 (TYK2) allosteric inhibitor deucravacitinib, the first oral pyruvate kinase (PK) activator mitapivat, the Janus kinase 1 (JAK1) selective inhibitor abcrocitinib, the JAK2 selective inhibitor pacritinib and the broad-spectrum fibroblast growth factor receptor (FGFR) inhibitor futibatinib. This review briefly describes the discovery background, research and development process, synthesis routes and clinical efficacy and safety of small molecule kinase modulators approved by the FDA in 2022, hoping to provide ideas and methods for further research on kinase modulators.

Progress in the Treatment of Antisense Oligonucleotides in Duchenne Muscular Dystrophy / 罕见病研究

In recent years, antisense oligonucleotide (ASO) has been very active in the field of rare disease research and development, especially in Duchenne muscular dystrophy, where it made a major breakthrough. Duchenne muscular dystrophy (DMD) is a rare childhood myopathy caused by mutations in the dystrophin gene. Currently, the four ASO drugs approved internationally for DMD are all targeted at dystrophin, including eteplirsen, golodirsen, viltolarsen and casimersen. They all belong to phosphorodiamidate morpholino oligomers (PMO) antisense oligonucleotide drugs, so that their pharmacokinetic characteristics are similar. The drugs quickly spread to other tissues after intravenous administration. Because of the electrical neutrality of the PMO, they have a low binding rate to plasma proteins and are quickly metabolized by the kidney and excreted in the urine as archetypes. In addition, the likelihood of drug-drug interactions of ASO is low. Existing clinical studies have shown that they have certain clinical benefits and good tolerability, bringing new options for DMD treatment. This paper mainly discusses the pharmacological effects, pharmacokinetic characteristics, efficacy, and safety of ASO drugs for the treatment of DMD, hoping to provide scientific reference for the rational and safe clinical use of such drugs.

An evaluation of safety and efficacy of nadifloxacin 1% ointment versus mupirocin 1% ointment in Indian children with skin and soft tissue infection

Background: Although nadifloxacin has been shown to be effective in the treatment of skin & soft tissue infections (SSTI), there is a paucity of data comparing its efficacy and safety with other antibacterials, especially in Indian paediatric population. Therefore, objective of this study was to compare the safety and efficacy of nadifloxacin with mupirocin in children with SSTI.Methods: This was a single-centre, open label, randomized, parallel group, comparative study in 60 children of <12 years of age with SSTI. Test group (n=30) received nadifloxacin 1% ointment and reference group (n=30) received mupirocin 1% ointment, to be applied twice daily. Patients were followed up at day 4, 8 and 15. Efficacy of the study drugs was evaluated by clinical and bacteriological cure rate. Safety was assessed by reporting of adverse events.Results: Baseline characteristics of enrolled patients were comparable between treatment groups and all 60 patients completed the study. At Day 15, 100.0% cases among nadifloxacin group and 96.7% cases among mupirocin group achieved clinical cure (p=0.313). The most common bacteria found in culture were Gram positive cocci in both the groups (86.7% in nadifloxacin and 58.8% in mupirocin group). None of the cases in any of the groups showed bacteriological presence at day 15. No adverse event was reported in any of the treatment groups during the study duration.Conclusions: Nadifloxacin was found to be equally efficacious and safe to mupirocin in the treatment of SSTI in Indian pediatric population.

Safety and efficacy of palonosetron compared in prevention of postoperative nausea and vomiting in patients undergoing elective major surgery under general anaesthesia

Background: Post-operative nausea and vomiting continues to be a common side effect of surgery and anaesthesia, affecting the economics of medical care, as well as the degree of patients’ satisfaction, comfort and quality of life.The objective of the present study were to compare the efficacy and safety of palonosetron versus placebo for prophylaxis of early onset (within 24 hours post-surgery) and late onset (24-72 hours post-surgery) post-operative nausea or vomiting in patients undergoing elective major surgery under general anaesthesia.Methods: A prospective, randomized, parallel group, two arm, double blind placebo controlled trial was conducted on n=100 indoor patients undergoing elective major surgeries were enrolled into the present study.Results: The patients showing complete response were 32 (64%) in palonosetron group and 19 (38%) in the placebo group (p<0.05) in the 0-24 hour time interval. The patients receiving palonosetron showed higher complete response rates in the 0-24 hour and 0-72 hour time intervals. 42 patients (84%) on palonosetron and 30 (60%) on placebo showed complete control of vomiting in 0-24 hour period. Adverse events related to the drug were reported in 5 patients (10%) in palonosetron group as compared to 3 patients (6%) in placebo group.Conclusions: A single prophylactic 0.075 mg IV dose of palonosetron effectively reduced the occurrence and severity of nausea and vomiting and delayed the time to emesis and treatment failure in the early as well as the overall postoperative period of 72 hours.

A comparison of Levobupivacaine and Bupivacaine in caudal anesthesia in children undergoing sub-umbilical operations

@#<p style="text-align: justify;"><strong>BACKGROUND:</strong> Caudal epidural anesthesia is commonly performed in conjunction with general anesthesia. Bupivacaine and Levobupivacaine are used in epidural blockade that provide anesthesia and analgesia intraoperative and post-operatively.</p><p style="text-align: justify;"><strong>OBJECTIVES:</strong> To compare the intraoperative and postoperative efficacy and safety of Bupivacaine and Levobupivacaine in children undergoing elective sub-umbilical operations under general and caudal anesthesia.</p><p style="text-align: justify;"><strong>METHODS:</strong> Randomized control trial done in Philippine Children's Medical Center. Sixty-one subjects aged 6-months -8 years old, ASA I-II, undergoing subumbilical operations were randomly grouped to receive Bupivacaine and Levobupivacaine during anesthesia induction. Hemodynamic parameters, Bromage, and CHIPPS were recorded.</p><p style="text-align: justify;"><strong>RESULTS:</strong> Results suggest both drugs have a significant effect in lowering heart rate and MAP. Bromage scores for patients from both groups are consistent at 0. The number of patients with a CHIPPS classification of 4-10, is significantly higher for bupivacaine group than levobupivacaine group.</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> Both Bupivacaine and Levobupivacaine provide adequate analgesia intraoperatively with no reports of intraoperative movement, increased inhalational agent concentration and additional intravenous analgesics. Post-operatively, no adverse effects and motor block was noted however Levobupivacaine has a longer efficacy as it required lesser rescue does post-operatively compared to Bupivacaine. </p>

Clinical analysis on blood exchange transfusion in treating 142 cases of neonatal severe hyperbilirubinemia / 国际检验医学杂志

Objective To explore the cause constituents of neonatal severe hyperbilirubinemia and the clinical efficacy and safety of blood exchange transfusion treatment .Methods 142 neonates with severe hyperbilirubinemia conducted the blood exchange transfusion therapy .The levels of serum total bilirubin ,indirect bilirubin and direct bilirubin and the change of blood routine indica-tors were analyzed before and after blood exchange transfusion .Results The main causes leading to neonatal severe hyperbilirubi-nemia were bacterial infection(28 .20% ) ,glucose-6-phosphate dehydrogenase(G6PD) deficiency(27 .50% ) and pregnant women with ABO blood group incompatibility (16 .20% ) .The levels of serum total bilirubin ,indirect bilirubin ,direct bilirubin and blood routine indicators after operation in neonates with severe hyperbilirubinemia were significantly lower than those before operation , the differences were statistically significant (P<0 .05) .The total bilirubin swap exchange was (54 .40 ± 9 .90)% .The intraoperative adverse reactions rate was 3 .50% .The postoperative thrombocytopenia occurrence rate was 72 .00% .Conclusion The blood ex-change transfusion for treating neonatal severe hyperbilirubinemia possesses has clinical significance ,but the hematology and bio-chemical indicators monitoring should be strengthened for avoiding adverse reactions occurrence .

In vitro and in vivo evaluation of efficacy and safety of photoprotective formulations containing antioxidant extracts

ABSTRACT Chronic exposure to solar radiation could contribute to premature skin aging and skin cancer. Skin presents its own antioxidant defense, however when defenses are out of balance, reactive oxygen species could damage biological structures. In the present work, an oil-in-water photoprotective emulsion was developed and Bauhinia microstachya var. massambabensis Vaz, Fabaceae, extracts at 1% (obtained by extraction with different solvents) were added to this emulsion. In vitro and in vivo efficacy and safety of the formulations were evaluated. Spectrophotometric methods and in vivo Colipa test were performed to evaluated efficacy of the formulations, through sun protection factor (SPF) determination and UVA protection factor assessment. To the in vitro safety assessment HET-CAM, CAM-TBS and Red Blood Cell tests were performed. Results showed that both extracts contributed to a higher in vivo photoprotection (SPF 18) when compared to the formulation without extract (SPF 13), this result could be attributed to the antioxidant activity of the plant extracts that act by capturing reactive oxygen species. Concerning safety, all formulations were considered non-irritant according to in vitro tests. Formulations containing extracts could be considered efficient and safe for cosmetic use since they presented higher sun protection factor and passed the toxicity tests.

Clinical efficacy and safety of azithromycin versus amoxicillin-clavulanic acid in the treatment of some acute respiratory infections in children:systematic evaluation / 国际药学研究杂志

Objective To systematically evaluate the clinical efficacy and safety of azithromycin(Az)versus amoxicillin-cla?vulanic acid(A-Cva)in the treatment of some acute respiratory infections in children. Methods Pubmed,EMBase,Medline,Co?chrane Library and CJFD were retrieved to collect the randomized controlled trial(RCT)of their clinical efficacy and safety in the treat?ment of acute respiratory infections in children. The methodological quality of included studies was evaluated.The RevMan 5.2 software was chosen for data analysis. Results Twenty RCTs involving 4980 pediatric patients were included for assessment of the clinical effi?cacy. Meta-analysis showed that Az had more significant effect on the treatment of some bacterial repiratory infections in children〔OR=0.78,95%CI(0.65,0.93),P=0.007〕than A-Cva. In the treatment of upper respiratory infections,acute otitis media and so on,Az had more significant effect〔OR=0.75,95%CI(0.62,0.91),P=0.003〕;in the treatment of lower respiratory infections,such as community acquired pneumonia and so on,Az and A-Cva acid had the similar effect〔OR=1.20,95%CI(0.62,2.33),P=0.58〕. Thirteen RCT in?volving 3474 pediatric patients were included for assessment of the clinical safety. Meta-analysis shows that the difference between Az and A-Cva is statistic significant in the treatment of some bacterial repiratory infections in children〔OR=0.49,95%CI(0.40,0.60),P<0.000 01〕. Conclusion Overall,Meta-analysis shows that Az is more effective and safer in the treatment of some bacterial repiratory infections in children than A-Cva.

Clinical efficacy and safety of azithromycin versus amoxicillin-clavulanic acid in the treatment of some acute respiratory infections in children: Systematic evaluation / 国际药学研究杂志

Objective To systematically evaluate the clinical efficacy and safety of azithromycin (Az) versus amoxicillin-clavulanic acid (A-Cva) in the treatment of some acute respiratory infections in children. Methods Pubmed, EMBase, Medline, Cochrane Library and CJFD were retrieved to collect the randomized controlled trial (RCT) of their clinical efficacy and safety in the treatment of acute respiratory infections in children. The methodological quality of included studies was evaluated. The RevMan5.2 software was chosen for data analysis. Results Twenty RCTs involving 4980 pediatric patients were included for assessment of the clinical efficacy. Meta-analysis showed that Az had more significant effect on the treatment of some bacterial repiratory infections in children (OR=0.78, 95%CI (0.65,0.93), P=0.007) than A-Cva. In the treatment of upper respiratory infections, acute otitis media and so on, Az had more significant effect (OR=0.75, 95%CI (0.62,0.91), P=0.003); in the treatment of lower respiratory infections, such as community acquired pneumonia and so on, Az and A-Cva acid had the similar effect (OR=1.20, 95%CI(0.62, 2.33), P=0.58). Thirteen RCT involving 3474 pediatric patients were included for assessment of the clinical safety. Meta-analysis shows that the difference between Az and A-Cva is statistic significant in the treatment of some bacterial repiratory infections in children (OR=0.49, 95%CI (0.40, 0.60), P<0.000 01). Conclusion Overall, Meta-analysis shows that Az is more effective and safer in the treatment of some bacterial repiratory infections in children than A-Cva.

Comparison of Formulation Property and Therapeutic Safety of Paclitaxel between Generic Products / 医薬品情報学

<b>Background: </b>Because generic medicines reduce the financial burden on patients and medical insurance providers, they become more popular year after year.  However, there are still few reports that analyze the efficacy and safety of generic medicines, especially in terms of their characteristics and side effects.<br><b>Methods: </b>Paclitaxel is an antineoplastic frequently used with good results in the treatment of breast cancer, ovarian cancer, gastric cancer, and angiosarcoma, but fat solubility is high and various kinds of adverse events, such as myelosuppression and arthralgia, peripheral neuropathy, and alcohol hypersensitivity are known to develop.  We investigated the efficacy, characteristics, and the incidence of adverse events for the generic product of paclitaxel.<br><b>Results: </b>Differences were found for the generic version in terms of the characteristics and preparation time.<br><b>Conclusion: </b>The incidence of adverse events was not significant, suggesting that the generic version could be a reasonable substitute.

Ultrafiltration in patients with decompensated heart failure and diuretic resistance: an Asian centre's experience

<p><b>INTRODUCTION</b>Diuretics are the mainstay of therapy for restoring the euvolaemic state in patients with decompensated heart failure. However, diuretic resistance remains a challenge.</p><p><b>METHODS</b>We conducted a retrospective cohort study to examine the efficacy and safety of ultrafiltration (UF) in 44 hospitalised patients who had decompensated heart failure and diuretic resistance between October 2011 and July 2013.</p><p><b>RESULTS</b>Among the 44 patients, 18 received UF (i.e. UF group), while 26 received diuretics (i.e. standard care group). After 48 hours, the UF group achieved lower urine output (1,355 mL vs. 3,815 mL, p = 0.0003), greater fluid loss (5,058 mL vs. 1,915 mL, p < 0.0001) and greater weight loss (5.0 kg vs. 1.0 kg, p < 0.0001) than the standard care group. The UF group also had a shorter duration of hospitalisation (5.0 days vs. 9.5 days, p = 0.0010). There were no differences in the incidence of 30-day emergency department visits and rehospitalisations for heart failure between the two groups. At 90 days, the UF group had fewer emergency department visits (0.2 vs. 0.8, p = 0.0500) and fewer rehospitalisations for heart failure (0.3 vs. 1.0, p = 0.0442). Reduction in EQ-5D™ scores was greater in the UF group, both at discharge (2.7 vs. 1.4, p = 0.0283) and 30 days (2.5 vs. 0.3, p = 0.0033). No adverse events were reported with UF.</p><p><b>CONCLUSION</b>UF is an effective and safe treatment that can improve the health outcomes of Asian patients with decompensated heart failure and diuretic resistance.</p>

Efficacy and Safety of Adalimumab in Moderately to Severely Active Cases of Ulcerative Colitis: A Meta-Analysis of Published Placebo-Controlled Trials

BACKGROUND/AIMS: To evaluate the efficacy and safety of adalimumab (ADA) in moderately to severely active ulcerative colitis (UC) patients who are unresponsive to traditional therapy. METHODS: Electronic databases, including the PubMed, Embase, and Cochrane databases, were searched to April 20, 2014. UC-related randomized controlled trials (RCTs) that compared ADA with placebo were eligible. Review Manager 5.1 was used for data analysis. RESULTS: This meta-analysis included three RCTs. ADA was considerably more effective compared with a placebo, and it increased the ratio of patients with clinical remission, clinical responses, mucosal healing and inflammatory bowel disease questionnaire responses in the induction and maintenance phases (p<0.05), as well as patients with steroid-free remission (p<0.05) during the maintenance phase. Clinical remission was achieved in a greater number of UC cases in the ADA 160/80/40 mg groups (0/2/4 week, every other week) compared with the placebo group at week 8 (p=0.006) and week 52 (p=0.0002), whereas the week 8 clinical remission rate was equivalent between the ADA 80/40 mg groups and the placebo group. Among the patients who received immunomodulators (IMM) at baseline, ADA was superior to the placebo in terms of inducing clinical remission (p=0.01). Between-group differences were not observed in terms of serious adverse events (p=0.61). CONCLUSIONS: ADA, particularly at doses of 160/80/40 mg (0/2/4 week, every other week), is effective and safe in patients with moderate-to-severe UC who are unresponsive to traditional treatment. Concomitant IMM therapy may improve the short-term therapeutic efficacy of ADA.

Efficacy and safety of Tonglin Powder in the treatment of benign prostatic hyperplasia / 中华男科学杂志

<p><b>Objective</b>To investigate the effect and safety of oral Tonglin Powder in the treatment of benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>We conducted a randomized controlled study on 100 BPH patients, aged 40－85 years, treated with Tonglin Powder (treatment group, n=50) or terazosin (control group, n=50), all for 3 months. Then we obtained the International Prostate Symptom Score (IPSS), quality of life score (QoL), prostate volume, postvoid residual urine volume (PVR), urine routine indexes, and liver and kidney function indexes from the patients and compared them between the two groups before and after treatment.</p><p><b>RESULTS</b>The baseline data of the patients in the treatment and control groups were as follows, IPSS (22.24±7.33) vs (21.40±8.24), QoL 4 (2－6) vs 4 (2－6), prostate length 45 (30－65) vs 45 (39－65) mm, prostate width 35 (21－54) vs 36 (26－57) mm, and PVR 10 (5－100) vs 10 (10－100) ml, none with statistically significant difference between the two groups (P>0.05). After treatment, the patients of the treatment group, in comparison with those of the control, showed remarkable decreases in IPSS (11.60±6.49 vs 15.38±7.34, P=0.008) and QoL (2 ［0－5］ vs 3 ［1－6］, P=0.01). No statistically significant differences were observed between the treatment and control groups in prostate length (47 ［38－67］ vs 47.5 ［38－67］ mm), prostate width (36 ［26－57］ vs 36.5 ［31－57］ mm), and PVR (10 ［8－100］ vs 10 ［8－70］ ml) (P>0.05). The Nimodipine method of evaluation showed that the excellence rate of therapeutic effectiveness was significantly higher in the treatment than in the control group (40% vs 8%, P<0.001), and so was the total effectiveness rate (82% vs 64%, P=0.043).</p><p><b>CONCLUSIONS</b>Tonglin Powder can effectively improve the symptoms of BPH, such as difficult urination, and hence the patient's quality of life.</p>

Efficacy and Safety of Autologous Adipose-derived Stem Cells Transplantation in Patients with Type 2 Diabetes Mellitus / 中国医科大学学报

Objective to evaluate the clinical efficacy and safety of ADSCs infusion in patients with type 2 diabetes mellitus(t2DM). Methods Autologous ADSCs were cultured and identified. totally 48 cases of type 2 diabetes patients were divided into two groups:24 cases in A group re-ceived ADSCs and conventional treatment,while the other 24 cases in B group received conventional treatment. With 15 months′follow-up,FPG,2h-PGh,HbA1c,FC-P,AUCC,insulin medication changes and security on post-treatment 3,6,12 and 15 months were calculated. Results the AD-SCs which cultured met the clinical application of standards. FPG,2h-PGh and HbA1c in both groups were significantly decreased,and the values in A group were more impressive than B. there were significant improvement in FC-P,AUCC and insulin of A group compared with B group. there was not treatment related adverse events. Conclusion the clinical data demonstrate that the treatment with ADSCs can improve metabolic control and beta cell function in patients with t2DM. Moreover,the safety of the treatment method was considerable.

Retrospective Analysis of Patients Treated with Cetuximab plus FOLFIRI for Previous Irinotecan-combined Chemotherapy in Metastatic Colorectal Cancer

PURPOSE: Many reports about efficacy of cetuximab in the prolongation of survival have been published. Especially, the combination of cetuximab and FOLFIRI has a high activity even in prior irinotecan refractory metastatic colorectal cancer (mCRC). Beside small number of patients, we are trying to evaluate the efficacy and safety of cetuximab combined with FOLFIRI for patients who prior irinotecan chemotherapy had failed. METHODS: A retrospective analysis of 26 patients treated with cetuximab with FOLFIRI from July 2006 to August 2007 was done. All patients had already been treated with FOLFIRI chemotherapy in 1st line or 2nd line regimens for mCRC. The initial dose of cetuximab was 400 mg/m2 at the 1st week, after which the dose was 250 mg/m2 weekly plus FOLFIRI biweekly. We defined 1 cycle as 8 weeks, and the responses were evaluated at week 8. RESULTS: The median follow-up period was 6.2 (1.1~13.9) months. After 8 weeks, 50% of the patients had a partial response, and the disease control rate was 57.5%. The median time to progression was 3 months. EGFR expression and tumor response had no correlation (P=0.07). Skin reaction and tumor response (median time to progression) had a significant correlation (P= 0.022). Cetuximab did not increase the toxicity associated with FOLFIRI, except for an acneiform rash. CONCLUSIONS: Cetuximab combined with FOLFIRI chemotherapy was effective in treating mCRC patients after FOLFIRI regimen chemotherapy.

3 Year Results of Tacrolimus in Kidney Transplantation: Single Center Experience / 대한이식학회지

PURPOSE: Results of the US randomized, comparative, multicenter study demonstrated that tacrolimus (Tac) was equivalent to cyclosporine (CyA) in 1-year patient and graft survival in recipients of cadaveric renal transplants. However, the incidence and severity of acute rejection was significantly lower in Tac-treated patients compared with CyA-treated patients. This retrospective, non-randomized single center study represents results of follow-up to 3 years posttransplant. METHODS: A total of 97 kidney transplant recipients were included; 41 received Tac-based immunosuppression, and 56 received CyA-based immunosuppression and followed for 3 years posttransplant. Serious adverse events were also monitored over 3 years. RESULTS: The three-year patient survival rates were 95.0% and 96.5% for Tac and CyA, respectively (P=NS). Corresponding graft survival rates were 90.2% and 91.0%, respectively (P=NS). However, the incidence of acute rejection was significantly less in the Tac-group compared with the CyA-group (17.1% vs. 35.7%, P=0.043). The rate of crossover was significantly higher in the CyA-group (4.9% vs. 21.4%, P=0.013). Renal function at 3 years was similar in both treatment groups. The incidence of posttransplant diabetes mellitus (PTDM), head-ache and alopecia was significantly less in the CyA-group, and that of hypertension, hypercholesterolemia after transplantation was significantly less in Tac-group. The incidence of hirsutism and gingival hyperplasia was negligible in Tac-group. Incidence of hand tremor, hyperkalemia, bacterial and viral infection, and malignancy was comparable in both groups. The incidence of PTDM was significantly less in CyA-group (26.8% vs. 7.1%, P=0.008). Nine (81.8%) of the 11 Tac patients with PTDM were off of insulin at 3 years. CONCLUSIONS: Tacrolimus is a very effective primary immunosuppressive agent in renal transplant recipient. The reduced incidence of acute rejection along with decreased incidence of hypertension and hyperlipidemia after transplantation suggests potential long-term advantage with the use of this drug.

Primary Immunosuppression with Tacrolimus in Renal Transplantation: Single Center Experience / 대한이식학회지

PURPOSE: Tacrolimus (FK-506) represents a major advance in the prevention of rejection following solid organ transplantation. Previous clinical trials in Japan, Europe, and the US suggest that tacrolimus is an effective primary immunosuppressive agent in kidney transplantation. This prospective, non-randomized single center study was done to confirmed the efficacy of tacrolimus in kidney transplantation. METHODS: A total of 50 renal transplant recipients who followed-up at least one year after transplantation was included in this study. Thirty six cases (72%) recived triple drug therapy consists of tacrolimus, mycophenolate mofetil (MMF), and low dose steroid. RESULTS: The overall incidence of acute rejection was 10%, all episodes of rejection were treated effectively with steroid pulse therapy. The incidence of treatment failure was six percent. One and two year graft survival were 98% and 96%, respectively. Adverse effects of tacrolimus therapy included tremor of the hand (56%), diarrhea (34%), alopecia (26%), hyperkalemia (22%), nephrotoxicity (18%), post transplant diabetes mellitus (14%), hypertension (14%), and hypercholesterolemia (10%). However, the incidence of gum hypertrophy and hirsutism were 6% and 2%, respectively. CONCLUSION: This short-term study indicates that tacrolimus appears to provide safe and effective primary immunosuppression in kidney transplantation.

Efficacy and Safety of Risperidone in Mood Disorders / 신경정신의학

OBJECTIVE: Although typical neuroleptics are commonly used in the treatment of bipolar disorder and psychotic depression, newer atypical antipsychoticss, like risperidone, may be more effective and better tolerated. This study evaluated the efficacy and safety of lithium/risperidone combination therapy in patients with mood disorders. METHODS: A total of 97 patients were included if they met DSM-IV criteria for bipolar I disorder, manic episode and major depressive disorder with psychotic feature and were treated with lithium/risperidone combination therapy and lithium/haloperidol combination therapy. Patients were rated using the CGI(Clinical global impression) GAF(Global assessment of functioning) Adverse events also assessed by medical personnel. RESULTS: Of 97 patients, 81 were diagnosed with bipolar I disorder, manic episode and 16 with major depressive disorder with psychotic feature. 81 patients who diagnosed with bipolar manic disorder were divided into two groups, with lithium/risperidone combination group and lithium/haloperidol combination group. There was no significant difference in age, sex, baseline CGI scores, and baseline GAF scores between two groups. 31 patients who received lithium and risperidone(2.07+/-0.46)were much more improved based on CGI scores than 50 patients who received lithium and haloperidol(2.58+/-0. 85) 25(80.6%)of lithium/risperidone combination group were rated much improved or very much improved, and 25(50%)of lithium/haloperidol combination group were rated response. Mean dose of risperdidone in responders(CGI< or =)is lower than partial respnders(CGI=3)4.50+/-1.92mg/d versus 4.88+/-3.31mg/d) While 16%(8 of 50)patients discontinued haloperidol and lithium because of delirium and confusion, lithium/risperidone combination group did not experienced intolerable side events. No patients was experienced worsening of manic symptoms while receiving lithium/risperidone. Antidepressant/risperidone combination group were much more improved based on CGI and GAF score. CONCLUSIONS: This study suggests risperidone is effective and well tolerated when added to lithium. We found no evidence of risperidone leading to an induction of manic symptoms.

Effectiveness of Cipol-N(R) in Primary Living Donor Kidney Transplant Patients: Open-Label, Multi-Center Study / 대한이식학회지

Cyclosporine (CsA) has been one of the main immunosuppressants after kidney transplantation since its introduction in Korea. There was remarkable improvement of graft survival in kidney transplantation with CsA, compared with azathioprine. Cipol-N(R)(Chong Kun Dang, Korea), microemulsion gelatin capsule formulation of CsA, is a new generic drug. This pure domestic brand of CsA was tested for bioequivalence in healthy adults compared with the reference drug of the same formulation, Sandimmun-Neoral(R)(Novartis, Switzerland) in 1997. This open-label, multi-center study is designed to evaluate the efficacy of Cipol-N(R) in primary kidney transplant recipients for 6 months after transplantation. A total of 59 patients from 4 medical centers were enrolled in the study. Maintenance immunosuppressive protocol was based on CsA and steroid dual therapy, which was induced 2 days prior to the operation. Acute rejection was diagnosed with clinical or pathological clue. Clinical criteria for the diagnosis of acute rejection were oliguria, graft swelling and tenderness, rising serum creatinine, fever, and papillary swelling and increased vascular resistant index on Doppler ultrasonography. Steroid pulse therapy was used as primary treatment. Steroid resistant acute rejection was treated with anti-lymphocyte agents such as OKT3, ATG, or ALG. The primary efficacy endpoint was onset of acute rejection or treatment failure, defined as graft loss, death, or premature termination from the study for any reason. Incidence and severity of acute rejection, actual survival rate of patient and graft, function of the graft, pharmacokinetics of the Cipol-N(R), and the primary efficacy variables were evaluated 6 months after transplantation. All enrolled patients were included in the primary analyses of efficacy on the basis of intent to treat. Mean age of the patients was 37.1 10.4 years old. Male and female ratio was 42:17. There were 38 related pairs, which included 5 HLA identical and 33 HLA haplo-identical matches, and 21 unrelated pairs. A total of 10 patients were withdrawn from the study before post- transplant 6 months. The causes for premature withdrawal were patient's request without specific reason (6), partially rescued acute rejection (3), and patient's death (1). There were 27 episodes of acute rejection in 25 patients, which were diagnosed clinically (11) and pathologically (16). Steroid pulse therapy and anti-lymphocyte agent were used in 24 and 3 cases respectively. There were 4 patients, who showed partial rescue but no graft loss due to acute rejection. Patient and graft survival was 98.3% at post-transplant 6 months. Serum creatinine concentration showed 1.3-1.7 mg/dl all through the study period, which meant relatively stable graft function. Mean daily doses of Cipol-N(R) at post-transplant 1 and 6 months were 325 and 300 mg respectively. With this short term study, we can report that Cipol-N(R) showed relatively good efficacy in primary living donor kidney transplantation. Further study is needed for the evaluation of long term efficacy and safety.

Effectiveness of Cipol-N(R) in Primary Living Donor Kidney Transplant Patients: Open-Label, Multi-Center Study / 대한이식학회지

Cyclosporine (CsA) has been one of the main immunosuppressants after kidney transplantation since its introduction in Korea. There was remarkable improvement of graft survival in kidney transplantation with CsA, compared with azathioprine. Cipol-N(R)(Chong Kun Dang, Korea), microemulsion gelatin capsule formulation of CsA, is a new generic drug. This pure domestic brand of CsA was tested for bioequivalence in healthy adults compared with the reference drug of the same formulation, Sandimmun-Neoral(R)(Novartis, Switzerland) in 1997. This open-label, multi-center study is designed to evaluate the efficacy of Cipol-N(R) in primary kidney transplant recipients for 6 months after transplantation. A total of 59 patients from 4 medical centers were enrolled in the study. Maintenance immunosuppressive protocol was based on CsA and steroid dual therapy, which was induced 2 days prior to the operation. Acute rejection was diagnosed with clinical or pathological clue. Clinical criteria for the diagnosis of acute rejection were oliguria, graft swelling and tenderness, rising serum creatinine, fever, and papillary swelling and increased vascular resistant index on Doppler ultrasonography. Steroid pulse therapy was used as primary treatment. Steroid resistant acute rejection was treated with anti-lymphocyte agents such as OKT3, ATG, or ALG. The primary efficacy endpoint was onset of acute rejection or treatment failure, defined as graft loss, death, or premature termination from the study for any reason. Incidence and severity of acute rejection, actual survival rate of patient and graft, function of the graft, pharmacokinetics of the Cipol-N(R), and the primary efficacy variables were evaluated 6 months after transplantation. All enrolled patients were included in the primary analyses of efficacy on the basis of intent to treat. Mean age of the patients was 37.1 10.4 years old. Male and female ratio was 42:17. There were 38 related pairs, which included 5 HLA identical and 33 HLA haplo-identical matches, and 21 unrelated pairs. A total of 10 patients were withdrawn from the study before post- transplant 6 months. The causes for premature withdrawal were patient's request without specific reason (6), partially rescued acute rejection (3), and patient's death (1). There were 27 episodes of acute rejection in 25 patients, which were diagnosed clinically (11) and pathologically (16). Steroid pulse therapy and anti-lymphocyte agent were used in 24 and 3 cases respectively. There were 4 patients, who showed partial rescue but no graft loss due to acute rejection. Patient and graft survival was 98.3% at post-transplant 6 months. Serum creatinine concentration showed 1.3-1.7 mg/dl all through the study period, which meant relatively stable graft function. Mean daily doses of Cipol-N(R) at post-transplant 1 and 6 months were 325 and 300 mg respectively. With this short term study, we can report that Cipol-N(R) showed relatively good efficacy in primary living donor kidney transplantation. Further study is needed for the evaluation of long term efficacy and safety.