Madopar scientific update |
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2010 Mar-Apr;33(2):61-6.
Zangaglia R, Stocchi F, Sciarretta M, Antonini A, Mancini F, Guidi M, Martignoni E, Pacchetti C.
Parkinson's Disease and Movement Disorders Unit, IRCCS Neurological Institute C. Mondino, Pavia, Italy.
Clinical experiences with levodopa methylester (melevodopa) in patients with Parkinson disease experiencing motor fluctuations: an open-label observational study.
INTRODUCTION: Slow gastric emptying decreasing levodopa (LD) bioavailability contributes to motor fluctuations in Parkinson disease (PD). Melevodopa (LD methylester), ensuring rapid duodenal absorption, has been proposed as rescue therapy for afternoon off periods. OBJECTIVE: To assess daily motor fluctuations by multiple administrations of Sirio (Chiesi Farmaceutici SpA, Parma, Italy) (melevodopa/carbidopa) in PD patients. PATIENTS AND METHODS: In this open-label naturalistic study, 75 PD patients (group A) completely switched standard LD (Sinemet or Madopar) with Sirio at an equivalent dosage (800-1000 mg/d). One hundred nineteen PD patients (group B) partially replaced their standard LD (Sinemet) with Sirio at an equivalent dosage (400-500 mg/d) while continuing Stalevo 100. In both groups, the observational period lasted 6 months. Assessments included an on/off diary, the Unified Parkinson's Disease Rating Scale (motor examination [UPDRS II] and activities of daily living [UPDRS III]), the dyskinesia scale, and an adverse event profile. RESULTS: Group A showed a significant reduction of afternoon off hours at 6 months (P < 0.05). Forty-five patients (69%) reported a subjective early onset of on motor response. Twelve patients (18.5%) reported its shorter duration. The dyskinesia scale score remained unchanged. Ten patients (13.3%) discontinued melevodopa for gastric intolerance. Group B showed at 6 months a significant reduction of total hours of daily off periods (P < 0.05), particularly in the morning (P < 0.01) and afternoon (P < 0.05). Seventy subjects (59%) expressed positive judgment on quickness of onset of on motor response. The dyskinesia scale score was unchanged. No significant adverse events were reported. CONCLUSIONS: Switching PD patients with motor fluctuations to melevodopa, particularly in the presence of entacapone, could optimize critical periods of the day such as the morning delay on and afternoon off periods.
2009 Jun;34(3):345-54.
Zhang TT, Song M, Hang TJ, Xu XF, Wen AD, Yang L, Jia L.
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China.
Pharmacokinetic profile of talipexole in healthy volunteers is not altered when it is co-administered with Madopar (co-beneldopa).
OBJECTIVES: To investigate the pharmacokinetics of talipexole hydrochloride tablets and the potential influence of Madopar (benserazide and levodopa combination; co-beneldopa) tablets on talipexole's pharmacokinetics when the two tablets are co-administered orally to healthy Chinese volunteers. METHODS: A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to measure talipexole concentration in human plasma in an open-label, randomized, two-way crossover, single-dose study, with 1-week washout period. Healthy Chinese volunteers were randomized to receive talipexole tablets either alone or together with Madopar tablets by oral administration after an overnight fast. Serial blood samples were collected for a period of 36 h after the administration. Pharmacokinetic parameters C(max), t(max), t(1/2z), mean residence time (MRT), AUC(0-tau), AUC(0-infinity), CL(z)/F and V(z)/F were determined under the non-compartmental model. Pharmacokinetic values of talipexole administered alone to the subjects were compared with those administered simultaneously with Madopar to determine whether or not the differences were statistically significant. RESULTS: The subjects experienced mild gastrointestinal irritation when talipexole was administered alone as well as together with Madopar. For talipexole hydrochloride, there were no significant differences in the pharmacokinetic values between the two administrations. No pharmacokinetic differences based on gender were observed either. CONCLUSION: A single oral dose of Madopar co-administered with talipexole does not significantly change talipexole's pharmacokinetics in human.
2009 Aug 25;1286:230-8. Epub 2009 Jun 27.
Zhao XD, Cao YQ, Liu HH, Li FQ, You BM, Zhou XP.
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 Zhongshan Road, Nanjing 21002, Jiangsu Province, China.
Long term high frequency stimulation of STN increases dopamine in the corpus striatum of hemiparkinsonian rhesus monkey.
Long term subthalamic nucleus (STN) high frequency stimulation (HFS) can improve most symptoms of Parkinson's disease (PD) patients and decrease the dosage of antiparkinsonian drug such as Madopar. The mechanism of STN HFS for PD still remains elusive. We hypothesize that the level of dopamine (DA) and its metabolites in the corpus striatum is increased after long term STN HFS. The aim of this study was to examine the DA and its metabolites in the extracellular space of corpus striatum in hemiparkinsonian monkeys during long term STN HFS. Four rhesus monkeys were induced to hemiparkinsonian models by injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) through right internal carotid artery. Then two of them were underwent long term right STN HFS for the subsequent microdialysis sessions. Four microdialysis probe cannulas were implanted into bilateral putamen and caudate nucleus respectively. The microdialysis probe was put into the microdialysis probe cannula of bilateral putamen and caudate nucleus. Dialysates of extracellular space in corpus striatum were collected prior to STN HFS, and subsequently 8 h, 1 week, 1 month, 2 months, 8 months and 10 months after STN HFS. The level of DA and its metabolites were determined by high performance liquid chromatography and subthalamic nucleus electrochemical detection (HPLC-ECD). HFS significantly improved PD symptoms of the monkeys. Rotation evoked by apomorphine (APO) disappeared immediately after HFS pulse generator was turned on. The levels of DA and its metabolites in putamen and caudate nucleus of electrode side increased significantly at different time points after stimulation. Long term STN HFS significantly improved symptoms of hemiparkinsonian rhesus monkey, which might be due to the increase of dopamine and/or its metabolites in corpus striatum.
Int J Neurosci. 2009;119(8):1190-7.
Huang Y, Jiang X, Zhuo Y, Tang A, Wik G.
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. nanfanglihuang@163.com
Complementary acupuncture treatment increases cerebral metabolism in patients with Parkinson's disease.
We used positron emission tomography (PET) and the 18-flourodeoxyglucose tracer to study cerebral effects of complementary acupuncture in Parkinson's disease. Five patients received scalp-acupuncture and Madopa, while the other five had Madopa only. PET scans before and after 5 weeks of complementary acupuncture treatment show increased glucose metabolisms in parietal, temporal, occipital lobes, the thalamus, and the cerebellum in the light-diseased hemisphere, and in parietal and occipital lobes of the severe-diseased hemisphere. No changes were observed in the Madopa-only group. Acupuncture in combination with Madopa may improve cerebral glucose metabolism in Parkinson's disease.
2008 Dec;28(4):255-7.
Ren XM.
The First People' Hospital of Hangzhou in Zhejiang Province, Hangzhou 310006, China.
Fifty cases of Parkinson's disease treated by acupuncture combined with madopar.
OBJECTIVE: To search for an effective therapy for treating motor disorder due to Parkinson's disease (PD). METHODS: Fifty cases in a treatment group were treated by acupuncture combined with madopar, and 30 cases in a control group treated by madopar only. RESULTS: A total effective rate of 92% was achieved with obvious alleviation of motor disorder in the treatment group, which was significantly higher than that in the control group (P<0.05). CONCLUSION: Acupuncture can enhance therapeutic effects of western medicine and lessen the dose of the medicine needed.
2007 Jan 17;43(2):774-8. Epub 2006 Oct 19.
Wen AD, Jia YY, Luo XX, Bi LL, Chen XY, Zhong DF.
Department of Pharmacy, Xi'jing Hospital, Fourth Military Medical University, Xi'an 710032, PR China. adwen@fmmu.edu.cn
The effect of Madopar on the pharmacokinetics of ropinirole in healthy Chinese volunteers.
Ropinirole is a nonergoline dopamine D(2)-receptor agonist and has been proven to be effective in both monotherapy and combination therapy for idiopathic Parkinson's disease. The purpose of the present study was to examine the effect of Madopar on the pharmacokinetics of ropinirole in healthy Chinese volunteers by using liquid chromatography tandem mass spectrometry (HPLC/MS/MS). A single dose of 1mg ropinirole was given orally after administration of the placebo or Madopar (containing 200 mg levodopa and 50 mg benserazide) to six healthy males and six healthy females in a cross-over randomized study with a minimum washout period of 8 days. Pharmacokinetic parameters were calculated for both treatments. Coadministration of ropinirole and Madopar did not result in a notable change in rate or extent of availability of ropinirole, as shown by the ratios (90% confidence intervals) of 1.045 (0.900, 1.222) for C(max) (maximum plasma concentration) and 1.167 (1.086, 1.262) for AUC(0-inf) (the area under the concentration-time curve). Likewise, no significant difference in any of the other pharmacokinetic parameters [T(max) (the time needed to reach the C(max)), MRT (mean residence time), volume of distribution (V/F), and clearance (CL/F)] was observed between the treatment groups. No clinically relevant adverse effects were detected under either conditions and there are no pharmacokinetic grounds for adjusting the dose of ropinirole when given in combination with Madopar in Chinese patients.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2007 Sep;27(9):796-9.
Lian XF, Luo XD.
Guangdong Provincial Hospital of Traditional Chi-nese Medicine, Guangdong. fufu69118@yahoo.com.cn
[Effect of TCM treatment according to syndrome differentiation in enhancing curative effect and reducing side-effect of madopa] [Article in Chinese]
OBJECTIVE: To observe the effect of TCM treatment according to syndrome differentiation in en-hancing curative effect and reducing side-effect of madopa in patients with Parkinson' s disease (PD). METHODS: The trial was conducted in 101 PD patients with a prospective stratified randomized and controlled method. They were assigned to group 1 in which the patients of rigidity were treated with Pabing Recipe 1 (PR1) plus Madopa tablets, group 2 with those of tremor given Pabing Recipe 3 (PR3) plus Madopa tablets, and group 3 given a fixed Chinese recipe plus Madopa tablets as the control. The treatment course for all the groups was 3 months. Clinical efficacy was evaluated with unified Parkinson's disease rating scale (UPDRS) and the adverse reactions observed before and after treatment. RESULTS: After treatment, the 4 partial scores and the total score of UPDRS decreased significantly in group 2 (P<0.01), and the former of them and the total score declined in group 1 and 3 (P<0.01), the improvement was better in group 1 and 2 than that in group 3 (P<0.01); the improvement rate in group 1 to 3 was 95.5%, 100.0% and 83.7%, respectively, which was significantly higher in group 1 and 2 than that in group 3 (P<0.05). CONCLUSION: TCM treatment according to syndrome differentiation could improve the clinical symptoms and reduce complications in PD patients, which could enhance curative effect and reduce side-effect of madopa.
Zhongguo Zhen Jiu. 2007 Aug;27(8):562-4.
Chen XH, Li Y, Kui Y.
Traditional Therapy Center, Guangdong Provincial TCM Hospital, Guangzhou 510120, China.
[Clinical observation on abdominal acupuncture plus Madopa for treatment of Parkinson's disease] [Article in Chinese]
OBJECTIVE: To find out an effective therapy for Parkinson's disease. METHODS: Sixty cases were randomly divided into an abdominal acupuncture group and a control group, 30 cases in each group. The abdominal acupuncture group were treated with Madopa and abdominal acupuncture at Zhongwan (CV 12), Xiawan (CV 10), Qi-hai (CV 6) and Guanyuan (CV 4), etc. ; and the control group were treated with Madopa. RESULTS: After treatment of 3 courses, the effective rate was 90.0% in the abdominal acupuncture group and 83.3% in the control group with a significant difference between the two groups (P<0.05). CONCLUSION: Abdominal acupuncture combined with Madopa can elevate therapeutic effect of Madopa and reduce adverse effects of Madopa for the patient of primary Parkinson's disease.
Nan Fang Yi Ke Da Xue Xue Bao. 2006 Jan 20;26(1):113-6.
Jiang XM, Huang Y, Zhuo Y, Gao YP.
Department of Acupuncture and Moxibustion, College of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Therapeutic effect of scalp electroacupuncture on Parkinson disease.][Article in Chinese
The following study is to observe the therapeutic effect of scalp electroacupuncture on Parkinson disease (PD) of grade 1.5-3.0 on Hoehn-Yahr scale. The study using thirty patients with Parkinson disease were treated and the results concluded that Scalp electroacupuncture is effective and safe for therapy of Parkinson disease.
OBJECTIVE: To observe the therapeutic effect of scalp electroacupuncture on Parkinson disease (PD) of grade 1.5-3.0 on Hoehn-Yahr scale. METHODS: Thirty patients with Parkinson disease were randomized equally into the treatment group and control group. Patients in the treatment group were treated by scalp eletroacupuncture at the contralateral points of MS6, MS4, MS8, MS9 and MS14 in cases of unilateral lesions or at the bilateral points for bilateral lesions, with also medication with Madopar. The patients in the control group were given Madopar only. The scores of Webster scale and the motor function of United Parkinson's Disease Rating Scale (UPDRS) were used to for assessment before and after the therapeutic course (6 weeks). RESULTS: Tremor, rigidity and bradykinesia were obviously improved in both the groups (P<0.05). The difference in the score of Webster scale was not significant between the two groups (P>0.05), but the treatment group showed greater improvement in motor functions than the control group (P<0.05). CONCLUSION: Scalp electroacupuncture is effective and safe for therapy of Parkinson disease.
Diabetes Obes Metab. 2003 Jan;5(1):38-44.
Fischer S, Patzak A, Rietzsch H, Schwanebeck U, Kohler C, Wildbrett J, Fuecker K, Temelkova-Kurktschiev T, Hanefeld M.
Institute and Outpatient Department of Clinical Metabolic Research, Medical Faculty Carl Gustav Carus of the Technical University Dresden, Germany.
Influence of treatment with acarbose or glibenclamide on insulin sensitivity in type 2 diabetic patients.
The present investigation using 77 patients was to compare the effect of acarbose and glibenclamide on the insulin sensitivity in type 2 diabetes. The study results showed a more substantial improvement of glucose control under glibenclamide than under acarbose which, however, was not associated with an increase of insulin sensitivity.
AIM: The aim of our double-blind, placebo-controlled study was to compare the effect of acarbose and glibenclamide on the insulin sensitivity in type 2 diabetes. METHODS: We investigated 77 patients (mean age 58.7 years, mean BMI 27.3 kg/m2), treated by diet alone for at least 4 weeks. The subjects were randomized into three treatment groups for 16 weeks: 100 mg t.i.d. acarbose (n = 25) or 1 mg t.i.d. glibenclamide (n = 27) or one t.i.d. placebo (n = 25). Before and after therapy, the levels of fasting plasma glucose, glycosylated haemoglobin, fasting insulin, plasma glucose and insulin 1 h after a standardized breakfast were measured and insulin sensitivity determined by euglycaemic hyperinsulinaemic clamp test. RESULTS: After the treatment period, BMI in the acarbose and placebo group decreased significantly, whereas in the glibenclamide group a significant increase was observed. Fasting plasma glucose was only significant reduced under glibenclamide. The postprandial glucose decreased significantly after acarbose (13.8 vs. 11.4 mmol/l, p < 0.05) and glibenclamide treatment (14.6 vs. 11.4 mmol/l, p < 0.05) and was unchanged under placebo (13.8 vs. 13.7 mmol/l). The fasting insulin levels remained unchanged in all three groups, whereas postprandial insulin values increased significantly under glibenclamide. Neither acarbose nor glibenclamide significantly changed insulin sensitivity [acarbose: glucose disposal rate before treatment 2.3 mg/kg body weight/min/insulin, after treatment 3.2; glibenclamide 2.2 vs. 2.1; placebo 2.6 vs. 3.0]. CONCLUSIONS: Our results show a more substantial improvement of glucose control under glibenclamide than under acarbose which, however, was not associated with an increase of insulin sensitivity.
Am J Physiol Regul Integr Comp Physiol. 2005 Feb 17;
Savastano DM, Carelle M, Covasa M.
Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, PA, USA.
Serotonin-Type 3 receptors mediate intestinal polycose- and glucose- induced suppression of intake.
The conclusion of the present study is that a selective serotonin-type 3 (5-HT3) receptors participate in the inhibition of food intake by intraduodenal infusion of carbohydrate solutions through a post-hydrolytic, preabsorptive mechanism.
Ondansetron, a selective serotonin-type 3 (5-HT3) receptor antagonist, was used to test the hypothesis that duodenal infusion of isosmotic solutions of Polycose or its hydrolytic product glucose, suppressed intake through 5-HT3 receptors. Polycose suppressed sucrose intake across both concentrations infused (132mM, 7.6 +/- 0.6 ml; 263mM, 2.3 +/- 0.5 ml), compared to intake under control conditions (12.6 +/- 0.3 ml, P <0.001). Pretreatment with 1.0 mg/kg ondansetron attenuated reduction of sucrose intake induced only by the highest concentration of Polycose (4.6 +/- 0.8 ml, P=0.004). Dose response testing revealed that suppression of food intake by 263mM Polycose was attenuated by ondansetron administered at 1.0, 2.0, and 5.0mg/kg equally, but not when given at 0.125, 0.25, and 0.5 mg/kg. Acarbose, an alpha-glucosidase inhibitor, attenuated Polycose-induced suppression of food intake and pretreatment with 1.0 mg/kg ondansetron had no further effect. Suppression of intake following 990mM glucose, but not mannitol infusion, was attenuated by pretreatment with 1.0 mg/kg ondansetron. The competitive SGLT1 inhibitor, phloridzin had no effect on 60 min 990mM glucose-induced suppression of intake or the ability of ondansetron to attenuate this suppression of intake. Conversely, glucose-induced suppression of intake was attenuated by phloridzin at earlier time points, and further attenuated when rats were pretreated with 1.0 mg/kg ondansetron. Ondansetron administration alone had no effect on intake at any dose tested. We conclude that 5-HT3 receptors participate in the inhibition of food intake by intraduodenal infusion of carbohydrate solutions through a post-hydrolytic, preabsorptive mechanism.
Diabetes Care. 2005 Mar;28(3):736-44.
Padwal R, Majumdar SR, Johnson JA, Varney J, McAlister FA.
Department of Medicine, 2E3.22 Walter C. Mackenzie HSC, University of Alberta Hospital, 8440-112th St., Edmonton, AB, Canada, T6G 2B7.
A systematic review of drug therapy to delay or prevent type 2 diabetes.
The purpose of the study is to review the evidence for the prevention of type 2 diabetes by pharmacological therapies. For this randomized controlled trials and cohort studies examining the effect of oral hypoglycemic agents, antiobesity agents, antihypertensive agents, statins, fibrates, and estrogen on the incidence of type 2 diabetes were identified from different literature manuals. The study resulted that no single agent can be definitively recommended for diabetes prevention.
OBJECTIVE: To systematically review the evidence for the prevention of type 2 diabetes by pharmacological therapies. RESEARCH DESIGN AND METHODS: Randomized controlled trials and cohort studies examining the effect of oral hypoglycemic agents, antiobesity agents, antihypertensive agents, statins, fibrates, and estrogen on the incidence of type 2 diabetes were identified from MEDLINE, EMBASE, the Cochrane Controlled Trials Registry, and searches of reference lists. Two reviewers independently assessed studies for inclusion and performed data extraction. RESULTS: Ten studies of oral hypoglycemic agents and 15 studies of nonoral hypoglycemic agents were found. Oral hypoglycemic agents and orlistat are the only drugs that have been studied in randomized controlled trials with diabetes incidence as the primary end point. In the largest studies of 2.5-4.0 years' duration, metformin (relative risk [RR] 0.69, 95% CI 0.57-0.83), acarbose (0.75, 0.63-0.90), troglitazone (0.45, 0.25-0.83), and orlistat (hazard ratio [HR] 0.63, 95% CI 0.46-0.86) have all been shown to decrease diabetes incidence compared with placebo; however, follow-up rates varied from 43 to 96%. Current evidence for statins, fibrates, antihypertensive agents, and estrogen is inconclusive. In addition, the critical question of whether drugs are preventing, or simply delaying, onset of diabetes remains unresolved. CONCLUSIONS: Currently, no single agent can be definitively recommended for diabetes prevention. Future studies should be designed with diabetes incidence as the primary outcome and should be of sufficient duration to differentiate between genuine diabetes prevention as opposed to simple delay or masking of this condition.
Metabolism. 2005 Mar;54(3):387-90.
Fujisawa T, Ikegami H, Inoue K, Kawabata Y, Ogihara T.
Effect of two alpha-glucosidase inhibitors, voglibose and acarbose, on postprandial hyperglycemia correlates with subjective abdominal symptoms.
The present experiment was to assess the possible difference in effectiveness of 2 alpha-glucosidase inhibitors, voglibose and acarbose, the relationship between postprandial hyperglycemia and subjective abdominal symptoms. The results demonstrated that 50 mg acarbose and 0.3 mg voglibose had similar overall effects on postprandial hyperglycemia as well as subjective symptoms, but marked interindividual variation existed.
Abstract To assess the possible difference in effectiveness of 2 alpha-glucosidase inhibitors, voglibose and acarbose, the relationship between postprandial hyperglycemia and subjective abdominal symptoms was investigated. A total of 21 inpatients with type 2 diabetes were recruited to a single-center, 2-period, crossover trial. The subjects were given acarbose (150 mg/d) or voglibose (0.9 mg/d) under an isocaloric diet, and the postprandial (2 hours) increment in blood glucose level, M value which is a marker for fluctuation of blood glucose levels, and subjective abdominal symptom score were monitored. There was no significant difference between the 2 agents in postprandial increment in blood glucose level, M value, and subjective symptom score. When patients were divided according to subjective symptoms, however, the sum postprandial glucose increments were significantly different according to the agent ( P = .03), with favorable efficacy in patients in whom the alpha-glucosidase inhibitor caused abdominal symptoms, demonstrating a significant interaction ( P = .04) between treatment and symptomatic grouping. The results demonstrated that 50 mg acarbose and 0.3 mg voglibose had similar overall effects on postprandial hyperglycemia as well as subjective symptoms, but marked interindividual variation existed. Subjective symptoms may be a predictor of the divergent clinical response to each agent.
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Drug category:Antiparkinson agents
 Madopar scientific update
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