An analytical method based on ultra-performance liquid chromatography with positive ion electrospray ionization(ESI) coupled with tandem mass spectrometry(UPLC–MS/MS) was developed and validated for the determination...An analytical method based on ultra-performance liquid chromatography with positive ion electrospray ionization(ESI) coupled with tandem mass spectrometry(UPLC–MS/MS) was developed and validated for the determination of therapeutic peptide desmopressin in human plasma. A desmopressin stable labeled isotope(desmopressin d_8) was used as an internal standard. Analyte and the internal standard were extracted from200 μL of human plasma via solid-phase extraction technique using Oasis WCX cartridges. The chromatographic separation was achieved on an Aquity UPLC HSS T3 column by using a gradient mixture of methanol and 1 m M ammonium formate buffer as the mobile phase. The calibration curve obtained was linear(r^2≥0.99)over the concentration range of 1.01–200 pg/m L. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The results of the intra-and inter-day precision and accuracy studies were well within the acceptable limits. The proposed method was successfully applied to pharmacokinetic studies in humans.展开更多
Objective To evaluate the efficacy and safety of desmopressin on frequency and urgency in female patients with overactive bladder(OAB)and nocturia.Methods A selective database search was conducted to validate the effe...Objective To evaluate the efficacy and safety of desmopressin on frequency and urgency in female patients with overactive bladder(OAB)and nocturia.Methods A selective database search was conducted to validate the effectiveness of desmopressin in patients with OAB and nocturia.Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were utilised.The meta-analysis included 378 women(five studies)with OAB.The clinical outcomes and adverse events were analysed.Results The treatment strategy of all the studies included can be divided into three categories:(1)The effect of desmopressin compared with baseline,(2)desmopressin compared with placebo,and(3)desmopressin and anticholinergic combination versus desmopressin monotherapy.There was a significant(50%)reduction in nocturia and urgency episodes after using desmopressin alone.Combined desmopressin and anticholinergic led to a decrease in the frequency of nocturia voids when only using anticholinergic(65%vs.33.2%).The time increased in the middle to the first nightly voids in the combination arm(65.11 min;p=0.045).The mean incidence(standard deviation)of leak-free episodes was higher under desmopressin than under placebo in the first 4 h(62%[35%]vs.48%[40%])and in the first 8 h(55%[37%]vs.40%[41%]).The safety profile was comparable between treatments.Conclusion Available data indicate that desmopressin is efficacious in significantly reducing nighttime urine production,episodes of nocturia,and urgency episodes.The affectivity of the combination therapy was very high with least side effects for the treatment of OAB/nocturnal polyuria.展开更多
Objectives: To evaluate the efficacy of intranasal desmopressin compared with intramuscular diclofenac and combination of both in the treatment of acute renal pain caused by stone disease. Patients and methods: Ninety...Objectives: To evaluate the efficacy of intranasal desmopressin compared with intramuscular diclofenac and combination of both in the treatment of acute renal pain caused by stone disease. Patients and methods: Ninety patients (51 males and 39 females) presented to our hospital emergency department (Al-Yarmouk Teaching Hospital/Baghdad/Iraq) with the diagnosis of acute renal pain caused by urolithiasis. They were randomized into three equal groups;group A received desmopressin 40 μg intranasally (4 puffs, each puff equivalent to 10 micrograms), group B received intramuscular diclofenac 75 mg and group C received both desmopressin and diclofenac. A visual analogue scale was used to assess the pain intensity in the 3 groups at baseline, 10, 20 and 30 min after drugs administration. Results: At presentation, the pain intensity was similar in all three groups. For patients in group A, the initial pain score was 9.5 then it declined to 5.2, 3.7 and 3.7 at 10, 20 and 30 minutes after administration of desmopressin, and for patients in group B, the initial pain score was 9.8 then became 4.6, 2.9 and 2.3 at 10, 20 and 30 minutes after diclofenac, while for patients in group C, the initial pain score was 9.7 then became 4.8, 2.6 and 2.2 at 10, 20 and 30 minutes after administration of desmopressin and diclofenac. Conclusion: 40 μg intranasal desmopressin sprays can be used to relieve pain in patients with acute renal pain either alone or combined with diclofenac.展开更多
Background: Nocturnal enuresis is caused by a mismatch between nocturnal urine production and bladder capacity. Together with a presumed decreased arousability, this results in an inability to awaken in response to a ...Background: Nocturnal enuresis is caused by a mismatch between nocturnal urine production and bladder capacity. Together with a presumed decreased arousability, this results in an inability to awaken in response to a full bladder. According to recent findings, a disrupted sleep might play a role in the pathophysiology of enuresis. Case: A 7-year-old boy was diagnosed with primary nocturnal enuresis caused by nocturnal polyuria and a concomitant parasomnia, somnambulism. A polysomnographic study was performed before treating the nocturnal enuresis with the oral lyophylisate formulation of desmopressin (melt). After 1 day of treatment, both nocturnal enuresis and somnambulism disappeared. Treatment was ceased after six months. One week later, the child started to produce more urine and redeveloped nocturnal polyuria. Somnambulism reappeared followed by nocturnal enuresis two weeks later. The same treatment protocol was started up, resulting in disappearance of both nocturnal enuresis and somnambulism. Conclusion: This case report documents the beneficial effect of desmopressin melt on both nocturnal enuresis, caused by nocturnal polyuria, and a concomitant parasomnia in particularly somnambulism.展开更多
Women with nocturia are more sensitive to desmopressin, a synthetic arginine vasopressin (AVP) analogue, with significant antidiuretic responses to desmopressin orally disintegrating tablet (ODT) 25 μg, compared with...Women with nocturia are more sensitive to desmopressin, a synthetic arginine vasopressin (AVP) analogue, with significant antidiuretic responses to desmopressin orally disintegrating tablet (ODT) 25 μg, compared with men who require 58 μg to achieve similar responses. In children the current desmopressin dose recommendation to treat primary nocturnal enuresis (PNE) is the same for boys and girls. This post hoc analysis of data from a randomised, doubleblind single-dose study of 84 children with PNE aged 6 - 12 years explored gender differences in sensitivity to desmopressin in children. Following water loading to suppress endogenous AVP, placebo or desmopres-sin 30, 60, 120, 240, 360 or 480 μg was administered when urinary production reached >0.13 mL/min/kg. The endpoints of urinary osmolality and duration of urinary-concentrating action (DOA) (above three thresholds: 125, 200 and 400 mOsm/kg) were analysed to compare efficacy in boys and girls, in each treatment group. The DOA and urinary osmolality were similar in both genders in the desmopressin 120 - 480 μg groups. Boys receiving desmopressin ODT 30 - 60 μg tended to increased urinary osmolality and experienced 1 - 2 hours longer DOA than girls. The same pattern of higher values in boys compared with girls was seen for all measures of urinary osmolality. Conclusion: In a limited sample of pre-pubertal children the antidiuretic response to desmopressin was largely similar between genders, in contrast to findings in adults.展开更多
We investigated the efficacy of oral desmopressin in the treatment of adult nocturia. In an analytical study between 2007-2009 in Zahedan-Iran, Thirty patients ≥55 years with verified nocturia (≥two voids/night) wer...We investigated the efficacy of oral desmopressin in the treatment of adult nocturia. In an analytical study between 2007-2009 in Zahedan-Iran, Thirty patients ≥55 years with verified nocturia (≥two voids/night) were enrolled. Patients with a history of an obstructive cause of nocturia, those with diseases getting worse by the anti-diuretic affect of desmopressin and those with well-defined curable causes (e.g. cystitis) were excluded. Patients received 0.2 mg of oral desmopressin at bed time for a period of 3 weeks. p < 0.05 was taken as the significant level. All 30 patients enrolled completed the trial. Fourteen (47 %) patients receiving desmopressin had fewer than half the number of nocturnal voids relative to base line (p < 0.001). The mean number of nocturnal voids decreased from 4.6 to 2.4 (p < 0.001). Fatigue (10%), headache (3%) and dizziness (3%) were reported. All adverse events were of mild intensity and there were no instances of hyponatremia. Oral desmopressin is an effective treatment in patients with nocturia and is well-tolerated.展开更多
Female storage lower urinary tract symptoms are prevalent and bothersome. They are usually attributed to an overactive bladder and treated with antimuscarinics. Nevertheless, failure of conventional treatment to allev...Female storage lower urinary tract symptoms are prevalent and bothersome. They are usually attributed to an overactive bladder and treated with antimuscarinics. Nevertheless, failure of conventional treatment to alleviate nocturia in particular and epidemiological data suggesting that nocturnal polyuria is the only or a contributing factor to nocturia, has attracted interest in decreasing nighttime urine production as a method of managing nocturia. A reduction in urine production could also, at least temporarily, delay daytime storage symptoms by delaying bladder filling. Therefore, desmopressin, the synthetic analogue or naturally occurring antidiuretic hormone, could have a role in the management of female frequency, urgency and urgency incontinence. This work aims to review data on the use of desmopressin in females with storage symptoms. Available evidence indicates that desmopressin is efficacious in reducing nighttime urine production and episodes of nocturia, resulting in fewer sleep interruptions. This translates into improved quality of life. Desmopressin is also effective in postponing micturition, urgency and incontinence for several hours after being taken on demand. The tolerability profile of desmopressin is good and significantly improved compared to historical figures due to the introduction of new oral formulations, tailoring the dose according to gender and age and adhering to instructions for fluid restriction before administration. The incidence of hyponatremia, desmopressin's most important side-effect, is less than 3% in recent trials. The efficacy of desmopressin, combined with its improved safety profile, makes it an interesting method for treating female storage lower urinary tract symptoms.展开更多
Background：Blood loss after cardiac surgery can be caused by impaired platelet （PLT） function after cardiopulmonary bypass.Desmopressin or 1-deamino-8-D-arginine vasopressin （DDAVP） is a synthetic analog of vasop...Background：Blood loss after cardiac surgery can be caused by impaired platelet （PLT） function after cardiopulmonary bypass.Desmopressin or 1-deamino-8-D-arginine vasopressin （DDAVP） is a synthetic analog of vasopressin.DDAVP can increase the level of von Willebrand factor and coagulation factor Ⅷ,thus it may enhance PLT function and improve coagulation.In this study,we assessed the effects of DDAVP on PLT aggregation and blood loss in patients undergoing cardiac surgery.Methods：A total of 102 patients undergoing valvular heart surgery （from October 2010 to June 2011） were divided into DDAVP group （n =52） and control group （n =50）.A dose of DDAVP （0.3 μtg/kg） was administered to the patients intravenously when they were being rewarmed.At the same time,an equal volume of saline was given to the patients in the control group.PLT aggregation rate was measured with the AggRAM four-way PLT aggregation measurement instrument.The blood loss and transfusion,hemoglobin levels,PLT counts,and urine outputs at different time were recorded and compared.Results：The postoperative blood loss in the first 6 h was significantly reduced in DDAVP group （202 ± 119 ml vs.258 ± 143 ml,P =0.023）.The incidence of fresh frozen plasma （FFP） transfusion was decreased postoperatively in DDAVP group （3.8% vs.12%,P =0.015）.There was no significant difference in the PLT aggregation,urine volumes,red blood cell transfusions and blood loss after 24 h between two groups.Conclusions：A single dose of DDAVP can reduce the first 6 h blood loss and FFP transfusion postoperatively in patients undergoing valvular heart surgery,but has no effect on PLT aggregation.展开更多
BACKGROUND Diabetic ketoacidosis(DKA)and hyperglycemic hyperosmolar state(HHS)are common acute complications of diabetes mellitus with a high risk of mortality.When combined with hypernatremia,the complications can be...BACKGROUND Diabetic ketoacidosis(DKA)and hyperglycemic hyperosmolar state(HHS)are common acute complications of diabetes mellitus with a high risk of mortality.When combined with hypernatremia,the complications can be even worse.Hypernatremia is a rarely associated with DKA and HHS as both are usually accompanied by normal sodium or hyponatremia.As a result,a structured and systematic treatment approach is critical.We discuss the therapeutic approach and implications of this uncommon presentation.CASE SUMMARY A 62-year-old man with no known past medical history presented to emergency department with altered mental status.Initial work up in emergency room showed severe hyperglycemia with a glucose level of 1093 mg/dL and severe hypernatremia with a serum sodium level of 169 mEq/L.He was admitted to the intensive care unit(ICU)and was started on insulin drip as per DKA protocol.Within 12 h of ICU admission,blood sugar was 300 mg/dL.But his mental status didn’t show much improvement.He was dehydrated and had a corrected serum sodium level of>190 mEq/L.As a result,dextrose 5%in water and ringer's lactate were started.He was also given free water via an nasogastric(NG)tube and IV Desmopressin to improve his free water deficit,which improved his serum sodium to 140 mEq/L.CONCLUSION The combination of DKA,HHS and hypernatremia is rare and extremely challenging to manage,but the most challenging part of this condition is selecting the correct type of fluids to treat these conditions.Our case illustrates that desmopressin and free water administration via the NG route can be helpful in this situation.展开更多
文摘An analytical method based on ultra-performance liquid chromatography with positive ion electrospray ionization(ESI) coupled with tandem mass spectrometry(UPLC–MS/MS) was developed and validated for the determination of therapeutic peptide desmopressin in human plasma. A desmopressin stable labeled isotope(desmopressin d_8) was used as an internal standard. Analyte and the internal standard were extracted from200 μL of human plasma via solid-phase extraction technique using Oasis WCX cartridges. The chromatographic separation was achieved on an Aquity UPLC HSS T3 column by using a gradient mixture of methanol and 1 m M ammonium formate buffer as the mobile phase. The calibration curve obtained was linear(r^2≥0.99)over the concentration range of 1.01–200 pg/m L. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The results of the intra-and inter-day precision and accuracy studies were well within the acceptable limits. The proposed method was successfully applied to pharmacokinetic studies in humans.
文摘Objective To evaluate the efficacy and safety of desmopressin on frequency and urgency in female patients with overactive bladder(OAB)and nocturia.Methods A selective database search was conducted to validate the effectiveness of desmopressin in patients with OAB and nocturia.Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were utilised.The meta-analysis included 378 women(five studies)with OAB.The clinical outcomes and adverse events were analysed.Results The treatment strategy of all the studies included can be divided into three categories:(1)The effect of desmopressin compared with baseline,(2)desmopressin compared with placebo,and(3)desmopressin and anticholinergic combination versus desmopressin monotherapy.There was a significant(50%)reduction in nocturia and urgency episodes after using desmopressin alone.Combined desmopressin and anticholinergic led to a decrease in the frequency of nocturia voids when only using anticholinergic(65%vs.33.2%).The time increased in the middle to the first nightly voids in the combination arm(65.11 min;p=0.045).The mean incidence(standard deviation)of leak-free episodes was higher under desmopressin than under placebo in the first 4 h(62%[35%]vs.48%[40%])and in the first 8 h(55%[37%]vs.40%[41%]).The safety profile was comparable between treatments.Conclusion Available data indicate that desmopressin is efficacious in significantly reducing nighttime urine production,episodes of nocturia,and urgency episodes.The affectivity of the combination therapy was very high with least side effects for the treatment of OAB/nocturnal polyuria.
文摘Objectives: To evaluate the efficacy of intranasal desmopressin compared with intramuscular diclofenac and combination of both in the treatment of acute renal pain caused by stone disease. Patients and methods: Ninety patients (51 males and 39 females) presented to our hospital emergency department (Al-Yarmouk Teaching Hospital/Baghdad/Iraq) with the diagnosis of acute renal pain caused by urolithiasis. They were randomized into three equal groups;group A received desmopressin 40 μg intranasally (4 puffs, each puff equivalent to 10 micrograms), group B received intramuscular diclofenac 75 mg and group C received both desmopressin and diclofenac. A visual analogue scale was used to assess the pain intensity in the 3 groups at baseline, 10, 20 and 30 min after drugs administration. Results: At presentation, the pain intensity was similar in all three groups. For patients in group A, the initial pain score was 9.5 then it declined to 5.2, 3.7 and 3.7 at 10, 20 and 30 minutes after administration of desmopressin, and for patients in group B, the initial pain score was 9.8 then became 4.6, 2.9 and 2.3 at 10, 20 and 30 minutes after diclofenac, while for patients in group C, the initial pain score was 9.7 then became 4.8, 2.6 and 2.2 at 10, 20 and 30 minutes after administration of desmopressin and diclofenac. Conclusion: 40 μg intranasal desmopressin sprays can be used to relieve pain in patients with acute renal pain either alone or combined with diclofenac.
文摘Background: Nocturnal enuresis is caused by a mismatch between nocturnal urine production and bladder capacity. Together with a presumed decreased arousability, this results in an inability to awaken in response to a full bladder. According to recent findings, a disrupted sleep might play a role in the pathophysiology of enuresis. Case: A 7-year-old boy was diagnosed with primary nocturnal enuresis caused by nocturnal polyuria and a concomitant parasomnia, somnambulism. A polysomnographic study was performed before treating the nocturnal enuresis with the oral lyophylisate formulation of desmopressin (melt). After 1 day of treatment, both nocturnal enuresis and somnambulism disappeared. Treatment was ceased after six months. One week later, the child started to produce more urine and redeveloped nocturnal polyuria. Somnambulism reappeared followed by nocturnal enuresis two weeks later. The same treatment protocol was started up, resulting in disappearance of both nocturnal enuresis and somnambulism. Conclusion: This case report documents the beneficial effect of desmopressin melt on both nocturnal enuresis, caused by nocturnal polyuria, and a concomitant parasomnia in particularly somnambulism.
文摘Women with nocturia are more sensitive to desmopressin, a synthetic arginine vasopressin (AVP) analogue, with significant antidiuretic responses to desmopressin orally disintegrating tablet (ODT) 25 μg, compared with men who require 58 μg to achieve similar responses. In children the current desmopressin dose recommendation to treat primary nocturnal enuresis (PNE) is the same for boys and girls. This post hoc analysis of data from a randomised, doubleblind single-dose study of 84 children with PNE aged 6 - 12 years explored gender differences in sensitivity to desmopressin in children. Following water loading to suppress endogenous AVP, placebo or desmopres-sin 30, 60, 120, 240, 360 or 480 μg was administered when urinary production reached >0.13 mL/min/kg. The endpoints of urinary osmolality and duration of urinary-concentrating action (DOA) (above three thresholds: 125, 200 and 400 mOsm/kg) were analysed to compare efficacy in boys and girls, in each treatment group. The DOA and urinary osmolality were similar in both genders in the desmopressin 120 - 480 μg groups. Boys receiving desmopressin ODT 30 - 60 μg tended to increased urinary osmolality and experienced 1 - 2 hours longer DOA than girls. The same pattern of higher values in boys compared with girls was seen for all measures of urinary osmolality. Conclusion: In a limited sample of pre-pubertal children the antidiuretic response to desmopressin was largely similar between genders, in contrast to findings in adults.
文摘We investigated the efficacy of oral desmopressin in the treatment of adult nocturia. In an analytical study between 2007-2009 in Zahedan-Iran, Thirty patients ≥55 years with verified nocturia (≥two voids/night) were enrolled. Patients with a history of an obstructive cause of nocturia, those with diseases getting worse by the anti-diuretic affect of desmopressin and those with well-defined curable causes (e.g. cystitis) were excluded. Patients received 0.2 mg of oral desmopressin at bed time for a period of 3 weeks. p < 0.05 was taken as the significant level. All 30 patients enrolled completed the trial. Fourteen (47 %) patients receiving desmopressin had fewer than half the number of nocturnal voids relative to base line (p < 0.001). The mean number of nocturnal voids decreased from 4.6 to 2.4 (p < 0.001). Fatigue (10%), headache (3%) and dizziness (3%) were reported. All adverse events were of mild intensity and there were no instances of hyponatremia. Oral desmopressin is an effective treatment in patients with nocturia and is well-tolerated.
文摘Female storage lower urinary tract symptoms are prevalent and bothersome. They are usually attributed to an overactive bladder and treated with antimuscarinics. Nevertheless, failure of conventional treatment to alleviate nocturia in particular and epidemiological data suggesting that nocturnal polyuria is the only or a contributing factor to nocturia, has attracted interest in decreasing nighttime urine production as a method of managing nocturia. A reduction in urine production could also, at least temporarily, delay daytime storage symptoms by delaying bladder filling. Therefore, desmopressin, the synthetic analogue or naturally occurring antidiuretic hormone, could have a role in the management of female frequency, urgency and urgency incontinence. This work aims to review data on the use of desmopressin in females with storage symptoms. Available evidence indicates that desmopressin is efficacious in reducing nighttime urine production and episodes of nocturia, resulting in fewer sleep interruptions. This translates into improved quality of life. Desmopressin is also effective in postponing micturition, urgency and incontinence for several hours after being taken on demand. The tolerability profile of desmopressin is good and significantly improved compared to historical figures due to the introduction of new oral formulations, tailoring the dose according to gender and age and adhering to instructions for fluid restriction before administration. The incidence of hyponatremia, desmopressin's most important side-effect, is less than 3% in recent trials. The efficacy of desmopressin, combined with its improved safety profile, makes it an interesting method for treating female storage lower urinary tract symptoms.
文摘Background：Blood loss after cardiac surgery can be caused by impaired platelet （PLT） function after cardiopulmonary bypass.Desmopressin or 1-deamino-8-D-arginine vasopressin （DDAVP） is a synthetic analog of vasopressin.DDAVP can increase the level of von Willebrand factor and coagulation factor Ⅷ,thus it may enhance PLT function and improve coagulation.In this study,we assessed the effects of DDAVP on PLT aggregation and blood loss in patients undergoing cardiac surgery.Methods：A total of 102 patients undergoing valvular heart surgery （from October 2010 to June 2011） were divided into DDAVP group （n =52） and control group （n =50）.A dose of DDAVP （0.3 μtg/kg） was administered to the patients intravenously when they were being rewarmed.At the same time,an equal volume of saline was given to the patients in the control group.PLT aggregation rate was measured with the AggRAM four-way PLT aggregation measurement instrument.The blood loss and transfusion,hemoglobin levels,PLT counts,and urine outputs at different time were recorded and compared.Results：The postoperative blood loss in the first 6 h was significantly reduced in DDAVP group （202 ± 119 ml vs.258 ± 143 ml,P =0.023）.The incidence of fresh frozen plasma （FFP） transfusion was decreased postoperatively in DDAVP group （3.8% vs.12%,P =0.015）.There was no significant difference in the PLT aggregation,urine volumes,red blood cell transfusions and blood loss after 24 h between two groups.Conclusions：A single dose of DDAVP can reduce the first 6 h blood loss and FFP transfusion postoperatively in patients undergoing valvular heart surgery,but has no effect on PLT aggregation.
文摘BACKGROUND Diabetic ketoacidosis(DKA)and hyperglycemic hyperosmolar state(HHS)are common acute complications of diabetes mellitus with a high risk of mortality.When combined with hypernatremia,the complications can be even worse.Hypernatremia is a rarely associated with DKA and HHS as both are usually accompanied by normal sodium or hyponatremia.As a result,a structured and systematic treatment approach is critical.We discuss the therapeutic approach and implications of this uncommon presentation.CASE SUMMARY A 62-year-old man with no known past medical history presented to emergency department with altered mental status.Initial work up in emergency room showed severe hyperglycemia with a glucose level of 1093 mg/dL and severe hypernatremia with a serum sodium level of 169 mEq/L.He was admitted to the intensive care unit(ICU)and was started on insulin drip as per DKA protocol.Within 12 h of ICU admission,blood sugar was 300 mg/dL.But his mental status didn’t show much improvement.He was dehydrated and had a corrected serum sodium level of>190 mEq/L.As a result,dextrose 5%in water and ringer's lactate were started.He was also given free water via an nasogastric(NG)tube and IV Desmopressin to improve his free water deficit,which improved his serum sodium to 140 mEq/L.CONCLUSION The combination of DKA,HHS and hypernatremia is rare and extremely challenging to manage,but the most challenging part of this condition is selecting the correct type of fluids to treat these conditions.Our case illustrates that desmopressin and free water administration via the NG route can be helpful in this situation.
