Application of nalmefene hydrochloride in pediatric laryngeal mask anesthesia / 上海交通大学学报（医学版）

Objective: To evaluate clinical anesthetic effects of nalmefene hydrochloride in pediatric laryngeal mask anesthesia. Methods: Sixty pediatric patients who underwent short-time eye surgeries were randomly divided into nalmefene hydrochloride group (Group N) and the control group (Group C), 30 patients each group. At the end of the surgeries, patients of Group N and Group C were respectively given nalmefene hydrochloride at 0.25 μg/kg and 0.9% sodium chloride at the same volume intravenously. The situation of the patients' respiration recovery was recorded 1, 2, 3, 4 and 5 minutes after administration, including the time on which the patients' respiration was recovered and their laryngeal masks were removed. The sedation scores (Ramsay scores) and the incidence of adverse postoperative responses were recorded after the removal of the laryngeal mask. Results: The 5-minute respiration recovery rate was high in Group N, where the 3-minute respiration recovery rate was 83.0%, while only 16.7% in Group C. Besides, respiration recovery time [(3.17±0.78) min] and time for removing laryngeal mask [(4.10±0.95) min] in Group N were shorter than those of Group C (both P0.05). After removing laryngeal mask, the incidence of adverse responses was lower in Group N than that in Group C (P<0.05). Conclusion: Nalmefene hydrochloride is effective in shortening respiration recovery time and laryngeal masks removing time, but makes no difference in patients' sedative effects, with lower incidence of adverse postoperative respiratory responses.

Application of nalmefene hydrochloride in pediatric laryngeal mask anesthesia / 上海交通大学学报（医学版）

Objective·To evaluate clinical anesthetic effects of nalmefene hydrochloride in pediatric laryngeal mask anesthesia.Methods· Sixty pediatric patients who underwent short-time eye surgeries were randomly divided into nalmefene hydrochloride group (Group N) and the control group (Group C),30 patients each group.At the end of the surgeries,patients of Group N and Group C were respectively given nalmefene hydrochloride at 0.25 μg/kg and 0.9％ sodium chloride at the same volume intravenously.The situation of the patients' respiration recovery was recorded 1,2,3,4 and 5 minutes after administration,including the time on which the patients' respiration was recovered and their laryngeal masks were removed.The sedation scores (Ramsay scores) and the incidence of adverse postoperative responses were recorded after the removal of the laryngeal mask.Results· The 5-minute respiration recovery rate was high in Group N,where the 3-minute respiration recovery rate was 83.0％,while only 16.7％ in Group C.Besides,respiration recovery time [(3.17±0.78) min] and time for removing laryngeal mask [(4.10±0.95) min] in Group N were shorter than those of Group C (both P＜0.05).No significant difference was found in postoperative sedation scores between these two groups (P＞0.05).After removing laryngeal mask,the incidence of adverse responses was lower in Group N than that in Group C (P＜0.05).Conclusion· Nalmefene hydrochloride is effective in shortening respiration recovery time and laryngeal masks removing time,but makes no difference in patients' sedative effects,with lower incidence of adverse postoperative respiratory responses.

Determination of disodium edetate in nalmefene hydrochloride injection by HPLC / 国际药学研究杂志

Objective To establish a high performance liquid chromatography (HPLC) method for the determination of disodium edentate (EDTA-2Na) in nalmefene hydrochloride injection. Methods Content of EDTA-2Na in nalmefene hydrochloride injection was determined by HPLC. C18 Column was used. The mobile phase consisted of 0.3% tetrabutylammonium hydroxide solution-wateracetonitrile (20: 45: 35) with a flow rate of 1.0 ml/min, and the detection wavelength was 254 nm. The column temperature was 30°C and the injection volume was 20 µl. Results The quantification limit and detection limit were 0.199 and 0.060 µg/ml, respectively; the linear equation for the disodium edetate was Y=10.125X-0.216, and the calibration curves were linear within the range of 2.4593~ 7.3780 µg/ml (r=1.000). Each concentration of the average recovery was between 98~102% (n=9) (RSD%=0.58%). Conclusion The method can be used for the determination of EDTA-2Na in nalmefene hydrochloride injection, which is convenient, fast, sensitive and reproducible, with good precision, specificity and accuracy.

Effect of Nalmefene Hydrochloride on Expressions of Pulmonary β-endorphin and Interleukin-17 in Rats with Lung Ischemia-reperfusion Injury / 医药导报

Objective To study the protective effect of nalmefene hydrochloride on lung ischemia-reperfusion injury and its mechanism.Methods 40 rats were randomly divided into model group,high dose of nalmefene group,low dose nalmefene group and sham operation group equally(n =10).The lung ischemia-reperfusion model was established by occlusion of the left pulmonary hilum.The intravenous injection of nalmefene (20,10 μg·kg-1) was applied at 10 minutes before occlusion of the left pulmonary hilum in the high dose of nalmefene group and the low dose of nalmefene group,respectively.The sham operation group without occlusion of the left pulmonary hilum was not given any treatment.At 2 h after reperfusion,all rats were detected arterial blood gas value and then sacrificed.The specimens from the upper lobe of the left lung tissue were preserved to observe pulmonary lesions,detect the ratio of wet / dry weight and the expressions of β-endorphin and interleukin(IL)-17.Results Compared with the model group,the value of PCO2,the degree of pulmonary lesions,the ratio of wet / dry weight and the expressions of β-endorphin and IL-17 in lung tissue were significantly decreased (P ＜ 0.01),while the value of PO2 was significantly increased (P ＜ 0.01) in the low dose of nalmefene group.Compared with the low dose of nalmefene group,thevalue of PCO2,the degree of pulmonary lesions,the ratio of wet/dry weight and the expressions of β-endorphin and IL-17 in lung tissue were significantly decreased (P ＜ 0.01),while the value of PO2was significantly increased (P ＜ 0.01) in the high dose of nalmefene group.Conclusion Nalmefene hydrochloride may prevent lung ischemia-reperfusion injury in a dose dependent manner by reducing the production of β-endorphin and inhibiting the expression of IL-17 in lung tissue.

Determination of disodium edetate in nalmefene hydrochloride injection by HPLC / 国际药学研究杂志

Objective To establish a high performance liquid chromatography(HPLC)method for the determination of disodi-um edetate(EDTA-2Na)in nalmefene hydrochloride injection. Methods Content of EDTA-2Na in nalmefene hydrochloride injection was determined by HPLC. C18 Column was used. The mobile phase consisted of 0.3%tetrabutylammonium hydroxide solution-water-acetonitrile(20:45:35)with a flow rate of 1.0 ml/min,and the detection wavelength was 254 nm. The column temperature was 30℃and the injection volume was 20μl. Results The quantification limit and detection limit were 0.199 and 0.060μg/ml,respectively;the linear equation for the disodium edetate was Y=10.125X-0.216,and the calibration curves were linear within the range of 2.4593~7.3780 μg/ml(r=1.000). Each concentration of the average recovery was between 98~102%(n=9)(RSD%=0.58%). Conclusion The method can be used for the determination of EDTA-2Na in nalmefene hydrochloride injection,which is convenient,fast,sensitive and reproducible,with good precision,specificity and accuracy.

Clinical Efficacy of Nalmefene Hydrochloride in the Treatment of Patients with Traumatic Shock / 中国药师

Objective: To investigate the clinical efficacy of nalmefene hydrochloride in the treatment of patients with traumatic shock. Methods:Totally 62 cases of patients with traumatic shock were randomly divided into nalmefene treatment group (n=31) and the control group ( n =31 ) according to the random number table. The control group was given the conventional treatment, while nalmefene treatment group was treated with nalmefene hydrochloride additionally. The changes of hemodynamics, plasma TNF-αand vas-cular endothelial function index were compared between the groups. Results:The mean arterial pressure in 24h after the treatment signifi-cantly decreased when compared with that in 12h after the treatment of nalmefene treatment group, and the difference was statistically sig-nificant (P<0. 05);the heart rate in 12h and 24h after the treatment in nalmefene treatment group significantly decreased when com-pared with that before the treatment, and the differences were statistically significant (P<0. 05);the plasma TNF-αlevels in 24h after the treatment in nalmefene treatment group significantly decreased when compared with that in 12h after the treatment, and the difference was statistically significant (P<0. 05), and there was no significant difference in plasma TNF-α levels before the treatment and in 12h after the treatment (P<0. 05);the plasma NO and ET in 24h after the treatment in nalmefene treatment group significantly decreased when compared with that in 12h after the treatment, and the difference were statistically significant (P<0. 05);and there was no signifi-cant difference in plasma NO and ET before the treatment and in 24h after the treatment (P<0. 05);abnormality in electrocardiogram, routine blood tests, routine urine and liver and renal function examinations were not found, and no obvious adverse drug reactions were shown during the treatment course. Conclusion:Nalmefene hydrochloride combined with the conventional treatment in the patients with traumatic shock shows striking efficiency with notable effects on hemodynamics ( heart rate and mean arterial pressure) , which can reduce plasma TNF-α, NO and ET levels and shows significant research significance.

Clinical Efficacy of Nalmefene Injections in the Treatment of Patients with Severe Head Injury / 中国药师

Objective:To compare the clinical efficacy and safety of nalmefene hydrochloride injections and Naofukang injections in the treatment of the patients with severe head injury. Methods:Totally 60 cases of patients with severe head injury were randomly divided into the observation group and the control group. The two groups were all given the conventional therapy, such as dehydration, expansion and anti-infective therapy. On the basis of the conventional therapy, the observation group was treated with nalmefene hydro-chloride injections, 0. 4-0. 6 mg in 0. 9% sodium chloride injections, ivd, qd, while the control group was given Naofukang injections, 4-9 g in 5% or 10% glucose injections, ivd, qd. The treatment course was 2 weeks. After the 3-day treatment, the heart rhythm, the incidence of respiratory abnormalities and intracranial pressure were compared between the two groups. After the 10-day treatment, the total efficacy and complications in the two groups were also recorded and compared. Results:After the 3-day treatment, the incidence of abnormal heart rhythm and respiratory abnormalities in the observation group were significantly lower than that in the control group (P<0. 05), the intracranial pressure in the observation group was better than that in the control group (P<0. 05). After the 10-day treatment, the total effective rate of the observation group was 93. 3%, which was much higher than that in the control group ( P<0. 05). After the treatment, the incidence of respiratory infections, acid-base unbalance and upper gastrointestinal bleeding in the ob-servation group was significantly lower than that in the control group (P <0.05). Conclusion: The clinical efficacy of nalmefene hydrochloride injections in the treatment of patients with severe traumatic brain injury is significant with promising safety, which is bet-ter than that of Naofukang injections.

Effect of nalmefene hydrochloride adjuvant therapy on serum NO, endothelin and cardiac troponin I in patients with traumatic shock / 中国生化药物杂志

Objective To analyse effect of nalmefene hydrochloride adjuvant therapy on serum nitric oxide(NO), endothelin (ET) and cardiac troponin I ( cTnI) in patients with traumatic shock.Methods 48 patients who were diagnosed with traumatic shock were collected.All patients were randomly divided into experimental group and control group, 24 cases in each group.On the basis of conventional anti shock treatment, the control group were treated with naloxone, the patients in experimental group received nalmefene hydrochloride treatment, after treatment, the serum levels of NO, endothelin and cardiac troponin I were detected in all patients.Results After treatment, compared with control group, the serum level of NO was lower in experimental group(P<0.05);the serum level of ET was lower in experimental group(P<0.05);the serum level of cTnI was lower in experimental group(P<0.05).Conclusions Nalmefene hydrochloride adjuvant therapy could significantly reduce the serum levels of NO, ET and cTnI in patients with traumatic shock,control the development of the disease, prevent myocardial injury.

Determination of the residual orgamic solvents in Nalmefene Hydrochloride by headspace GC / 中国生化药物杂志

Objective To develop a headspace GC method for simultaneously determining the residual organic solvents Ethanol, Diethyl ether, Acetone, Dichloromethane, Ethyl acetate, and Tetrahydrofuran in Nalmefene Hydrochloride. Methods Samples dissolved in DMF and six organic residual organic solvents were separated on a DB 624 capillary column (30.0 m×0.32 mm,1.8μm) with a FID detector. The inlet temperature was 220℃and the FID detector temperature was 250℃. The column temperature rose by program:the initial temperature was 35℃, maintained for 8 min, raise to 180cwith a rate of 30℃/min, maintained for 5 min. The heated temperature of the headspace oven was 80℃, the heated time lasted 30 min, and the injection volume was 1.0 mL. Results Six residual orgamic solvents, including Ethanol, Diethyl ether, Acetone, Dichloromethane, Ethyl acetate, and Tetrahydrofuran in Nalmefene Hydrochloride were completely separated. It was appeared to present a good linearity within the experimental concentration. The limit of detection for Ethanol, Diethyl ether, Acetone, ichloromethane, Ethyl acetate, and Tetrahydrofuran were 0.25,0.076,0.15,0.55,0.26 and 0.30μg?mL-1.The method has a good average recovery. Conclusion The method is proved to be accurate and sensitive after validation. It is suitable to determine the residual orgamic solvents in Nalmefene Hydrochloride .

Impact of nalmefene hydrochloride on inflammatory reaction in rats with traumatic brain injury / 中华创伤杂志

Objective To observe the changes of TNF-α and NF-κB after different doses of nalmefene hydrochloride (NAL) therapy for traumatic brain injury (TBI) in an effort to identify the effect of NAL on TBI-induced inflammatory response and the possible mechanism.Methods A model of TBI in the rat was produced using the improved Feeney' s free-fall impact method.The animals were randomly divided into sham group,TBI group,TBI + large dose of NAL (ip,0.2 mg/kg) group (TBI + NAL1group),TBI + medial dose of NAL (ip,0.14 mg/kg) group (TBI + NAL2 group),TBI + small dose of NAL (ip,0.07 mg/kg) group (TBI + NAL3 group).Form of brain tissues in each group was observed and mRNA levels of TNF-α and NF-κB were measured by real-time quantitative PCR assay.Results HE staining revealed severe injury and inflammatory infiltration of brain parenchyma in TBI group ;on the contrary,the situation ameliorated in TBI + NAL1 group,TBI + NAL2 group and TBI + NAL3group,with especially obvious improvement in TBI + NAL2 group.In PCR assay,significant expression of NF-κB and TNF-α was observed at post-TBI days 1,3,5 and 7 (P ＜ 0.05),followed by great reverse after NAL therapy (P ＜ 0.05),particularly in TBI + NAL2 group.Conclusions NAL can reduce the inflammation response to TBI and promote post-injury recovery.Moreover,there exists a NAL concentration window.

Pharmacokinetics of Nalmefene hydrochloride in healthy volunteers / 重庆医科大学学报

Objective:To study the phamacokinetics of Nalmefene hydrochloride. Methods:30 healthy Chinese volunteers were assigned to 3 groups according to randomized design, and each group were given respectively a single intravenous administration dose of 0.5 mg, 1mg and 2mg of Nalmefene hydrochloride. The electrospray ionization positive selected reaction monitoring detections for Nalmefene hydrochloride and allyln-oroxymorphone (the internal standard) in the plasma and in the urine were used. The pharmaceutical parameters were calculated by 3P87 software. Results: The limit of the detection for Nalmefene hydrochloride was 0.0008 ng/ml in plasma and 0.0003 ng/ml in urine. There were good linear relationship range from 0.04 to 625ng/ml in plasma and 0.2 to 625 ng/ml in the urine. The variation coefficient in day and days, and the recoveries fitted the clinical pharmacokinetic study requirements. After a single intravenous administration of 0.5 mg,1mg, and 2mg of Na-lmefene hydrochloride, the obtained pharmacokinetic parameters were respectively as follows:Cmax were(1.74?0.48)?g/L,(4.17?1.08) ?g/L,(7.88?2.89) ?g/L;t1/2? were(12.83?3.98) h,(12.6?6.4) h, (10.58?3.74) h;V were (3.45?0.16) L/kg;(4.11?0.0716)L/kg、(4.25?0.56)L/kg;CL were (0.81?0.11) L/(h?kg), (0.85?0.15)L/(h?kg), (0.87?0.11) L/(h?kg);AUC0-∞ were (21.62?9.34) (ng/L)*h,(24.89?8.52) (ng/L)*h, (35?11.2) ng/L)*h;the urine accumulatived exc-retory rate were (78?21)%,(71?29)%,(78?19)%. Conclusion: The determination method for Nalmefene hydro-chloride in the plasma and in the urine by the electrosprayionization positive selected reaction monitoring detections is exclusive, accurate, sensitive and suitable. Pharmacokinetic characteristics in 3 groups of human treated with intravenous administration were described by a two-compartment model. The pharmaceutical characteristics of doxycycline hydrochloride in human body were linear in the range of 0.5~2.0 mg.