Azasetron Research Articles

Sustainable and efficient skin absorption behaviour of transdermal drug: The effect of the release kinetics of permeation enhancer

At present, how the release kinetics of permeation enhancers affected their enhancement efficacy on drug skin absorption and its molecular mechanisms remained unclear. Herein, the release kinetics of permeation enhancer (Plurol Oleique CC (POCC)) which involved release percent (PR), release duration (RD) and release kinetic constant (k) and its enhancement efficacy on drug skin absorption were investigated with in vitro skin retention study and in vitro skin permeation study, respectively. POCC released from the acidic-drug loading patches followed with the Higuchi release model and had short RD (8–16 h), resulting in its unsustainable enhancement efficiency for acidic drugs. However, POCC released from the basic-drug loading patches followed with zero-order model with long RD (12–24 h), inducing a sustainable and efficient enhancement efficiency for basic drugs. The lower variance of an innovative parameter permeation enhancement coefficient (CPE) represented the relatively sustainable and effective enhancement effect and was listed as followed: 0.20 (Zaltoprofen (ZPF)), 0.31 (Diclofenac (DCF)), 0.27 (Indomethacin (IMC)), 0.07 (Azasetron (AST)), 0.11 (Oxybutynin (OBN)) and 0.06 (Donepezil (DNP)). According to the results of FT-IR, MTDSC, 13C NMR spectra, molecular dynamics simulation, SAXS and Raman imaging, the Higuchi release model was caused by strong interaction between the acid drugs and pressure sensitive adhesive (PSA). This strong interaction induced faster diffusion speed of POCC from acidic-drug loading patches and make the swell degree of long periodicity phase (LPP) of stratum corneum (SC) lipids reached plateau early. The zero-order release model was because the weak interaction between basic drugs and PSA making most of POCC was still bound to PSA, which in turn lead to LPP swelled at a slow but sustainable process. In conclusion, zero-order release kinetic of POCC lead to sustainable and efficient penetration enhancement efficiency on basic drug, while the Higuchi release kinetic showed opposite effect for acidic drugs. A deep understanding of release kinetics of enhancer and its enhancement efficiency may drive the ideal selection of permeation enhancers and rational optimization of transdermal patches.

Effects of Dexmedetomidine on Postoperative Nausea and Vomiting in Adult Patients Undergoing Ambulatory Thyroidectomy: A Randomized Clinical Trial.

Background: Postoperative nausea and vomiting (PONV) is a common and disturbing problem in patients undergoing ambulatory thyroidectomy. This prospective trial aimed to explore whether dexmedetomidine (DEX) combined with azasetron (AZA) can further drop the incidence of PONV in patients undergoing ambulatory thyroidectomy compared with AZA.Methods: This single-center, randomized, double-blind trial involved 172 adult patients undergoing ambulatory thyroidectomy. The individuals were randomized to DEX + AZA group and AZA group. In the DEX + AZA group, patients received dexmedetomidine 0.5 μg kg−1 for 10 min and then the infusion rate was held at 0.1 μg kg−1 h−1 until the completion of the operation, while the same amount of 0.9% saline in the AZA group. At the completion of the surgery, 10 mg azasetron was administered to every patient in both groups. The primary outcome was the incidence of 24 h PONV after ambulatory thyroidectomy. The secondary outcomes included residence time in recovery room, pain scores, severity of nausea, and adverse events.Results: No significant difference was found in the incidence of 24-h PONV between the DEX + AZA group and the AZA group [36% (30 of 84) vs. 38% (32 of 84); relative risk, 0.94; 95% confidence interval (CI), 0.63–1.40; P = 0.749]. The incidence of severe nausea was similar between the DEX + AZA group and the AZA group [57% (12 of 21) vs. 43% (9 of 21); relative risk, 1.33; 95% CI, 0.72–2.50; P = 0.355].Conclusions: Intraoperative dexmedetomidine combined with azasetron failed to drop the incidence of 24-h PONV compared with azasetron alone in patients undergoing ambulatory thyroidectomy.

Application of intravenous flurbiprofen axeyil injection combined with sufentanil for postoperative analgesia of ovarian cancer radical operation

Objective To evaluate the efficacy and safety of flurbiprofen axeyil injection combined with sufentanil for postoperative patient undergoing ovarian cancer radical operation.Methods 60 postoperative patients undergoing radical ovarian cancer surgery were randomly divided into three groups with 20 cases in each group, including Sufentanil 150 μg (group S) ,Flurbiprofen Axeyil injection 200 mg (group F) ,Flurbiprofen Axeyil injection 100 mg plus Sufentanil 100 μg (group FS).The drugs in each group were added with Azasetron 10 mg and diluted to 100 ml, then infused by a pump in a rate of 2 ml/h.The visual analogue scale (VAS) and Ramesays scores were used to evaluate the analgesic effect at 0.5,2,4,8,12,24 and 48 h after surgery.The incidence of side effects was recorded.Results All the patients showed good pain relief with PCIA.The VAS of group F(3.3 +0.8) at 2 h after operation was slightly higher than that of group S (2.6 + 1.0) and SF (2.8 + 1.1) (P ＜ 0.05), which became similar 4 h later (P ＞0.05).In groups F (2.4 +0.8,2.3 +0.6) and FS(2.9 +0.8,2.6 ±0.4), the average Ramsay score was slightly lower than that in group S(3.8 +0.9,3.6 +0.5) (P ＜0.05).But the differences were not significant within 8 h after operation (P ＞ 0.05).The accidence rates of nausea, vomiting, itching, somnolence of group S(20％ ,15％ ,20％) were significantly higher than those in group F (5％ ,0,5％)and FS(5％,5％ ,5％) (P ＜0.05).No respiratory depression or abnormal bleeding occurred in three groups during the period of postoperative 48 hour.The amount of hydrothorax had no difference between 3 groups (P ＜0.05).Conclusions Intravenous postoperative analgesia with Flurbiprofen Axeyil injection combined with Sufentanil had a better analgesic effect than Sufentanil or Flurbiprofen Axeyil used alone, and it could significantly reduce the dose requirement of Sufentanil as well as its associated side effects. Key words: Flurbiprofen/AD; Sufentanil/AD; Ovarian neoplasms/SU ; Analgesia, patient-controlled

Clinical observation of combined Azasetron and low-dose dexamethasone for preventing postoperative nausea and vomiting in patients undergoing painless abortion surgery

Objective To observe the antiemetic effect of azasetron plus low-dose dexamethasone in patients undergoing painless abortion surgery.Methods 270 ASA physical status Ⅰ～Ⅱpatients scheduled for elective painless abortion surgery were randomly divided into 3 equal groups.Patients intravenously received saline(group A),azasetron(group B),azasetron plus low-dose dexamethasone(group C)respectively.Anesthesia was induced with propofol(3 mg/kg)in combination with fentanyl(0.6μg/kg).Patients were interviewed after 24 hours of the surgery by telephone.The incidence of postoperative nausea and vomiting was recorded.Results The overall incidence of POVA in group B and C were significantly lower than group A.There was no significant difference between group B and C.Conclusion Azasetron in combination with low-dose dexamethasone produced same antiemetic effect as azasetron alone in patients underwent painless abortion surgery. Key words: Azasetron; Propofol; Dexamethasone; Nausea; Vomit

The efficacy of combination chemotherapy with oxaliplatin for advanced colorectal cancer

Objective To observe the efficacy and toxicity of oxaliplatin (L-OHP) combined with 5-fluorouracil (5-FU) and leucovorin (LV) for advanced colorectal cancer, and to compare the clinical value of 2 week- or 3 week-regimen. Methods According to the chronology, 95 patients with advanced colorectal cancer were randomly divided into: ① treatment group 1 (47 cases): L-OHP 85 mg/m2, intravenous drip 2h for day 1; LV, intravenous drip 2 h for days 1 and 2; 5-fluorouracil (5-Fu) 400 mg/m2 were injected after LV,followed by 5-Fu 600 mg/m2, continuous intravenous drip 22 h, d1 、d2, repeated every 2w, at least 6 cycles. ②treatment group 2 (48 cases): L-OHP 130 mg/m2, intravenous drip 2 h, d1; LV 200 mg/m2, intravenous drip 2h,followed by 5-Fu 500 rag/d, intravenous drip 4 h for days 1 to 5, repeated every 3 weeks, at least 4 cycles. The two groups were injected Tropisetron 100 mg 30 min or Azasetron 10 mg for oral administration in order to prevent vomiting before, chemotherapy.Results The efficacy was similar in the two groups, the total efficacy achieved 46.8% and 41.6% (P>0.05); The incidence of adverse reactions were similar in the two groups. The main adverse reactions were gastrointestinal reactions, myclosuppression, neurological toxicity, and alopecia (P>0.05); CEA and CA-199 were significantly decreased after treatment (P 0.05). The median survival and median progression-free survival were significantly different (P<0.01). Conclusions L-OHP combined with LV and 5-FU is a relatively effective, less toxic regimen in the treatment of advanced colorectal cancer, and it is suggested to choose the standard 2 week-regime first. Key words: Oxaliplatin; 5-Fluorouracil ; Leucovorin; Advanced colorectal cancer; Combinationchemotherapy

Clinical investigation of azasetron to prevent nausea and vomiting on patients after ocular trauma surgery

目的 观察比较阿扎司琼(azasetron)预防眼外伤手术后恶心呕吐的效果.方法眼外伤手术75例,随机分为对照组(A组)、氟哌利多(droperidol)组(B组)和阿扎司琼组(C组),每组25例.在手术结束前,A、B、C组分别静脉注射生理盐水5mL、氟哌利多5 mg或阿扎司琼10 mg,观察每位患者用药后恶心呕吐发生情况.结果眼外伤手术后恶心呕吐的发生大多数在术后24 h内,呕吐发生率,C组小于B组(P＜0.05),B组小于A组(P＜0.05).结论本研究表明阿扎司琼是一种安全有效的预防眼外伤手术后恶心呕吐的药物。

Second-line chemotherapy with combined irinotecan and low-dose cisplatin for patients with metastatic gastric carcinoma resistant to 5-fluorouracil.

Although 5-fluorouracil (5-FU) is still the mainstay of systemic treatment for patients with metastatic gastric cancer, many patients do not show satisfactory response to this drug. We treated patients with metastatic gastric cancer resistant to 5-FU with a combination of irinotecan hydrochloride (I) and low-dose cisplatin (P). Twenty-one consecutive patients with advanced metastatic gastric cancer and performance status of 0-2, who had received prior chemotherapy with S-1, but had nonetheless shown unrelenting tumor progression, were treated with 60 mg/m(2) of I combined with 6 mg/m(2) of P, administered by intravenous infusion over 90 min following premedication with azasetron (I/low-P). I/low-P was repeated weekly for 3 weeks with the patient admitted to hospital, and thereafter, fortnightly on an outpatient basis. Seven, eight and six of the total of 21 patients had liver metastases, lymph node metastases and peritoneal dissemination, respectively. Objective response was observed in 11 of the 21 patients (52%; 95% confidence interval: 31-78%). Two (18%) and nine (82%) of these 11 patients exhibited complete and partial response, respectively. The median duration of the response was 7.9 months. The treatment regimen under study was tolerated very well by the patients. Thirteen of the 21 patients (62%) developed grade 1 or 2 leucopenia, which was the most common adverse reaction recorded. Diarrhea and nausea, grade I in all of the cases, occurred in five (22%) and nine (43%) patients, respectively. Based on its remarkable effectiveness, marked improvement in the quality of life of the patients, and the convenience of its administration, the I/low-P regimen is recommended as a promising second-line chemotherapeutic regimen for patients with metastatic gastric cancer resistant to 5-FU.