Mais les résultats doivent être attendus longtemps et il n'y a généralement pas de temps metronidazole prix L'autre cas, c'est que l'achat d'un ou d'un autre antibiotique dans une pharmacie classique nécessite des dépenses matérielles considérables et pas toutes les personnes ne peuvent acheter des produits pharmaceutiques aussi coûteux.

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Data and Results: Hemorrhage produced a decrease in hema­
IRL-1620 prevents beta amyloid (Aβ) induced oxidative stress
tocrit from ~49% to ~27%, which was similar in all the groups. and cognitive impairment
Sixty minutes following resusctiation with LR, blood lactate level Seema Briyal, Cortney Shepard, Anil Gulati was 10.2±0.6 mmol/L, however addition of centhaquin in LR Midwestern University, Downers Grove, IL, USA improved lactate level to 4.1±0.3 mmol/L. Similarly, following resusctiation with SAL, lactate level was 3.4±0.5 mmol/L, and Statement of Purpose, Innovation or Hypothesis: Alzheimer’s
addtion of centhaquin improved it to 2.0±0.3 mmol/L. Cardiovas­ disease (AD) is a progressive brain disorder leading to impair­ cular parameters signficantly improved following addition of ment of learning and memory. Incidence of AD is higher in dia­ centhaquin in either LR or SAL. Centhaquin improved the sur­ betic patients. Studies indicate that stimulation of ETB receptors vival following LR treatment from 78±10 mins to 387±38 mins, may provide neuroprotection. The present study was conducted and following SAL treatment from 144±22 mins to 326±55 mins. to investigate the involvement of ETB receptors in Aβ­induced Another experiment showed that centhaquin decreased the cognitive impairment in non­diabetic and diabetic rats.
requirement of NE by 10 folds in HS. In hemorrhaged rats, a 50% Description of Methods and Materials: The expression of ETB
decrease in systemic vascular resistance (SVR) was observed in receptors was studied using Western blotting. Parameters of oxi­ spite of infusion of a high dose (50 µg/100g/hour) of NE; whereas, dative stress assessed were malondialdehyde (MDA), glutathione only 36% decrease in SVR was observed following a low dose (GSH) and superoxide dismutase (SOD). Learning and memory (5 µg/100g/hour) infusion of NE in centhaquin treated rats.
behavior was assessed using the Morris water maze. Rats were Interpretation, Conclusion or Significance: Centhaquin
treated with Aβ(1­40) (6.67 µg, icv) was administered on day 1, 7 and improves the resuscitative effects of LR and SAL and increases 14 and all experiments were performed on day 15. Diabetes was the vascular responsiveness to NE in hemorrhaged rats.
induced by administering streptozotocin (45 mg/kg, ip) 3 days prior to Aβ injection. Rats were treated chronically with ETB receptor agonist (IRL­1620) and antagonist (BQ­788) for 14 days.
Single-dose Plasma PK Parameters of Arbaclofen, R-baclofen
Data and Results: Diabetic rats showed sluggish behavior and
and S-baclofen
decreased locomotion compared to non­diabetic rats, but there Glenn Meyer1, Gustavo Fischbein2, David Boyd1 was no difference in cognitive impairment or oxidative stress parameters following Aβ treatment in non­diabetic and diabetic 1Osmotica Pharmaceutical Corp, Wilmington, NC, USA; 2Osmotica rats. Aβ treatment produced no change in ETB receptor expres­ Pharmaceutical Argentina S.A., Buenos Aires, Argentina sion in the brain, and ETB receptor expression was not altered by IRL­1620 or BQ­788 treatment. A significant increase in levels of Statement of Purpose, Innovation or Hypothesis: Arbaclofen,
MDA and a concurrent decrease in GSH and SOD levels was the R­enantiomer of the GABAb agonist baclofen, is in develop­ observed following Aβ treatment in non­diabetic and diabetic ment, as the single enantiomer, for the treatment of spasticity due rats. IRL­1620 produced a significant (P<0.001) decrease to multiple sclerosis. We hypothesized that the PK parameters for (278.4±8.5 nmol/g wet tissue) in MDA level compared to the the R­enantiomer would be the same when administered alone vehicle group (516.1±14 nmol/g wet tissue) and reversed the versus administration as the racemic mixture.
decrease in GSH and SOD levels following Aβ treatment in non­ Description of Methods and Materials: A 4­arm, double blind,
diabetic and diabetic rats. In Morris water maze task, Aβ treated parallel group, dose­ranging PK study of arbaclofen and baclofen rats showed a significant (P<0.0001) impairment in spatial mem­ was conducted in healthy subjects to compare the plasma parame­ ory. Administration of IRL­1620 to Aβ treated rats produced a ters. Twelve subjects in each group received either arbaclofen doses significant improvement in learning and memory compared to the of 5, 7.5, or 10mg, or baclofen doses of 20mg, initially on Day 1 and vehicle group in both diabetic and non­diabetic rats. Changes then every six hours thereafter for four days after an up­titration induced by IRL­1620 were completely blocked by BQ­788.
period of nine days. Here we report the initial, single­dose results.
Interpretation, Conclusion or Significance: Aβ produced an incre­
Data and Results: On Day 1, initial single, equi­molar doses of
ase in oxidative stress parameters and loss of learning and mem­ the R­enantiomer produced similar PK results for arbaclofen and ory, which was significantly improved by ETB agonist, IRL­1620.
the R­enantiomer of baclofen. The p­values for AUC, Cmax, Tmax, and t1/2 were, 0.97, 0.43, 0.70, and 0.51 respectively. The same parameters for the S­enantiomer vs. R­enantiomer in the baclofen group were notably different with p­values less than Role of centhaquin in the resuscitation of hemorrhagic shock
Anil Gulati1, Manish S. Lavhale2, Suresh Havalad3 Interpretation, Conclusion or Significance: The R and
1Midwestern University, Downers Grove, IL, USA; 2Pharmazz, S­enantiomers of baclofen exhibit different ADME parameters. Inc., Naperville, IL, USA; 3Advocate Lutheran General Hospital, Arbaclofen ADME parameters are similar to those of R­baclofen when administered as the racemic mixture.
Statement of Purpose, Innovation or Hypothesis: Centhaquin
may have a role in resuscitative effect by improving the vascular Arbaclofen 10 mg
Baclofen 20 mg
responsiveness in the resuscitation of hemorrhagic shock (HS). It is our hypothesis that adding centhaquin to Lactated Ringer’s (LR) or PK Parameter*
Arbaclofen
R-baclofen S-baclofen
3% hypertonic saline (SAL) will enhance their resuscitative effect.
Description of Methods and Materials: Rats were anaesthe­
tized with urethane. The femoral vein was canulated for drug administration and femoral artery was cannulated for measuing mean arterial pressure (MAP). A calibrated pressure­volume cath­ eter (SPR­869) was placed into the left ventricle and data were analyzed using a LabChart­5.00 and PVAN analysis program. After completion of surgery, induction of HS was initiated by withdrawing blood from the right femoral artery to maintain the MAP between 35 and 40 mmHg for 30 minutes.
*­ all values are arithmetic means of single doses (SD) ABSTRACTS
for treatment of DPN, PHN and FM was developed. Subsequently, Population Pharmacokinetics-Pharmacodynamics of the 27 controlled clinical trials with data from >9500 patients, for drugs
G-Protein Coupled Receptor 40 (GPR40) Agonist TAK-875 in
evaluated across at least two indications (pregabalin, gabapentin Subjects with Type 2 Diabetes Mellitus (T2DM)
and duloxetine) and reporting LOCF imputed 0­10 points Likert or Majid Vakilynejad, Jing­tao Wu, Prabhakar Viswanathan, Vipin Brief Pain Inventory average pain scores were selected for analysis. A non­linear mixed­effects model­based meta­analysis of change Takeda Global Research & Development Center, Inc., Deerfield, IL, from baseline average pain score was conducted using NONMEM 7.
Data and Results: The final dose response model was an E
model with indication­dependent placebo and E parameters and Statement of Purpose, Innovation or Hypothesis:
common E for all drugs within an indication. For DPN only, E a highly selective and potent GPR40 agonist which causes glu­ was found to be dependent on placebo effect (i.e. E ­ E model cose­dependent insulin secretion and is being developed by was better than E model). There was no statistical evidence that Takeda for the treatment of T2DM. A sequential population ED for any of the three drugs differs across tested indications and pharmacokinetic­pharmacodynamic (PPKPD) model for TAK­875 therefore one ED parameter was used for each drug across indica­ was developed to estimate mean population PK and PD parame­ tions. The model­estimated placebo effect was ­1.5, ­0.9 and ­1.1 ters using TAK­875 concentrations and fasting plasma glucose points for DPN, PHN and FM, respectively; inter­trial standard­ (FPG) levels measured in a short­term 14 day clinical study.
deviation was 0.3 points. The model­estimated maximal effect was Description of Methods and Materials: Using historical glyce­
­1.6 points (E ­ E ) for DPN and ­2.2 and ­1.2 points (E ) for PHN mic data (13 clinical trials and ~8000 subjects from various Takeda and FM, respectively. Estimated ED values were 324, 1600 and 28 diabetes programs), an empirical linear mixed effect model was mg for pregabalin, gabapentin and duloxetine, respectively.
developed to predict long­term effects (changes in HbA1c) from Interpretation, Conclusion or Significance: Results from this
short­term changes (FPG levels at day 14). Data from a phase 1, analysis demonstrate higher placebo effect for DPN compared to double­blind, randomized, placebo­controlled, multiple rising­dose PHN and FM and greater maximal drug effect in PHN vs. DPN and study of TAK­875 25, 50, 100, 200 or 400 mg (n=45) or placebo FM. There was no evidence that the potency of the drugs differed (n=14) given orally for 14 days to T2DM patients were included.
Data and Results: The PK and FPG profiles were best described
using a two compartment model with first­order absorption and elimination processes and an Emax stimulatory indirect response CSF and Plasma PK Parameters of R-baclofen: Arbaclofen Versus
model, respectively. The inter­patient variability was included in the Racemic Mixture
the model as exponential errors for CL, V, and baseline FPG. The Glenn Meyer1, Gustavo Fischbein2, David Boyd1 model parameters were estimated precisely [CL/F=0.624 (%RSE=10) L/h, Vc/F=4.11 (%RSE=19), Ka = 0.0750 (%RSE=13) h­1, baseline Osmotica Pharmaceutical Corp, Wilmington, NC, USA; 2Osmotica FPG=172 (%RSE=3) mg/dL, EC50=1150 (%RSE=38%), ng/mL, Pharmaceutical Argentina S.A., Buenos Aires, Argentina Emax=0.349 (%RSE=13)] and the model was stable and predictive.
Statement of Purpose, Innovation or Hypothesis: Arbaclofen,
Interpretation, Conclusion or Significance: This modeling and
the R­enantiomer of the GABAb agonist baclofen, is in development simulation approach characterized the TAK­875 exposure­response for the treatment of spasticity due to MS. The PK parameters of oral relationship and suggested a dose range for Phase 2. Oral adminis­ R­baclofen in the CSF have not been previously reported. Animal tration of TAK 875 25­50 mg once per day is predicted to show an data suggests competitive transport for the R­ and S­enantiomers A1c reduction at week 12 that is comparable to sulfonylureas.
across the blood­brain barrier. We hypothesized this difference in transport into the CSF would be present in humans.
Description of Methods and Materials: A 4­arm, double­blind,
Efficacy of Pregabalin, Gabapentin and Duloxetine in Treatment
parallel group, dose­ranging PK study of arbaclofen and baclofen of Diabetic Neuropathic Pain, Postherpetic Neuralgia and
was conducted in healthy subjects to compare the plasma and CSF Fibromyalgia: A Model-Based Meta-Analysis
parameters. Twelve subjects in each group received oral arbaclofen Ahmed A. Othman1, Sandeep Dutta1, Walid Awni1, Jaap Mandema2 doses of 5, 7.5, or 10mg, or baclofen doses of 20mg every six hours 1Department of Clinical Pharmacology and Pharmacometrics, for four days after an up­titration period of nine days. Steady state Abbott Laboratories, Abbott Park, IL, USA; 2Quantitative PK parameters were calculated from samples taken on Day 14.
Data and Results: No difference was observed for AUC, Cmax,
and Cmin in the plasma or CSF for equi­molar doses of R­baclofen Statement of Purpose, Innovation or Hypothesis: The objec­
when administered as the single enantiomer or the racemic mixture.
tive of this work was to characterize the efficacy dose­response Interpretation, Conclusion or Significance: Plasma and CSF param­
relationship of drugs approved or evaluated for treatment of sev­ eters were not dose proportional in the arbaclofen treated groups. eral neuropathic pain indications: Diabetic Neuropathic Pain Plasma and CSF PK parameters of R­baclofen are not different when (DPN), Postherpetic Neuralgia (PHN), and Fibromyalgia (FM).
administered as the single enantiomer or the racemic mixture. The Description of Methods and Materials: A database of all pub­
competitive blood brain barrier transport of the R­ and S­enantiomers licly available efficacy information on drugs approved or evaluated observed in pre­clinical models was not observed in this study.
1123350: Table 1: R-baclofen PK Results
Treatment
AUCt ng*h/ml
Cmax ng/ml
Cmin ng/ml
AUCt ng*h/ml
Cmax ng/ml
Cmin ng/ml
ABSTRACTS
patient education is required about drug uses and stricter regula­ Many studies showed that information disseminated through the tory activities will be needful to promote rational drug uses in advertisement is inconsistent with the code of ethics. Thus this study aims to evaluate the authenticity and rationality of the pharmaceutical promotional drug literatures.
Description of Methods and Materials: In this prospective
observational study we collected 171 promotional pharmaceuti­ A Cross-sectional Study to Assess the Patients’ Satisfaction and
cal drugs literature from various departments such as Cardiology, Effectiveness of Complementary and Alternative Medicine
Medicine, Nephrology, Oncology Orthopedics, and pediatrics at (CAM) in four chronic diseases in a tertiary referral centre in
K.E.M. Hospital, Parel, Mumbai. The collected literatures were analyzed for rationality according to world health organization Mangesh S. Bhalerao, Pravin M. Bolshete, Balkrishna D. Swar, criteria (WHO) and authenticity of therapeutic claims made in Triveni A. Bangera, Vijaykumar R. Kolhe, Swapnil D. Bhowate, promotional literature were verified by accessing standard litera­ Mukund J. Tambe, Umesh B. Sonje, Meenal P. Wade, Nithya J. Data and Results: In this prospective observational study on
Department of clinical pharmacology, Seth GS Medical College & pharmaceutical promotional drug literatures showed that 19.30% KEM hospital Parel, Mumbai, Mumbai, India (33) were rational, 80.70% (138) were irrational, 49.12% (84) were authentic and 50.88% (87) were not authentic. Multinational com­ Statement of Purpose, Innovation or Hypothesis: The use of
panies showed 9.36% (16) rationale, 24.56% (42) irrational, Complementary and Alternative Medicine (CAM) is increasing and 19.88% (34) authentic, 14.62% (25) not authentic and non multi­ becoming an important treatment option for patients with chronic national companies showed 9.36% (16) rationale, 56.72% (97) diseases. The present study was conducted to assess the patients’ irrational, 29.83% (51) authentic and 35.67% (61) not authentic. satisfaction and extent of CAM use in four chronic diseases; Rheu­ Out of 171 promotional literatures 26.90% (46) were from diabetes matoid arthritis (RA), Diabetes mellitus (DM), Epilepsy and HIV.
blood pressure, 15.79% (27) from analgesics, 15.20% (26) from Description of Methods and Materials: The study was
antibiotics and 31% (53) from other therapeutic area.
approved by the IRB and conducted over a 16 week period in Interpretation, Conclusion or Significance: It was concluded
these diseases after written informed consent from participants. from this study that pharmaceutical companies did not follow the Key selection criteria were age more than 18 yrs and taking CAM WHO guidelines while promoting their drugs. They have only the along with established therapy. The Treatment Satisfaction Ques­ commercial motive rather than the ethical educational aspect. tionnaire for Medication (TSQM)TM was used to assess the satis­ Important information about contraindication, precautions, adverse faction in domains like Effectiveness, no Side Effect, Convenience drug reaction and drug interactions was usually missing. Non mul­ and Global Satisfaction. The domain scores ranged from 0 to 100 tinational pharmaceutical companies showed the more irrationality with higher scores representing greater satisfaction.
and non authenticity. There will be need of making stringent laws Data and Results: A total of 4664 patients were screened. Of
for ethical promotion of pharmaceutical drugs material.
these 1619 (34.71%) were found to be using CAM. Of these, 969/1619 (59.85%) declined to consent and thus only 650 were studied. The extent of use of CAM in DM was 63%, RA 42.73 %, HIV 26.19 % and Epilepsy 7.67%. Ayurveda was found to be most Plasma and CSF Levels of Arbaclofen Are Not Associated With
frequently used CAM 57.07 % (95% CI 53.27­60.89). Satisfaction Drowsiness
in terms of effectiveness and global satisfaction was highest in HIV Glenn Meyer1, Gustavo Fischbein2, David Boyd1 (69.43% and 69.24 % respectively) and least in RA (56.61 % and 1Osmotica Pharmaceutical Corp, Wilmington, NC, USA; 2Osmotica 54.13 % respectively). High scores were reported to “no side effect Pharmaceutical Argentina S.A., Buenos Aires, Argentina “domain in all four diseases indicating satisfaction with CAM.
Interpretation, Conclusion or Significance: The extent of use of
Statement of Purpose, Innovation or Hypothesis: Arbaclofen,
CAM in four chronic diseases in a tertiary referral centre was found the R­enantiomer of baclofen, is in development for spasticity due to be 34.71% .The users of CAM in DM, HIV and Epilepsy believed to multiple sclerosis. The primary dose limiting adverse event for that CAM were safe, effective and convenient with high satisfac­ racemic baclofen is drowsiness and sedation. We hypothesized tion. Given the potential interaction of CAM with conventional that the S­enantiomer was the primary cause of these events.
therapies, patients should be screened at least by history taking for Description of Methods and Materials: A 4­arm, parallel
use of CAM. Studies on the actual effectiveness may help physi­ group, double­blind, dose­ranging PK study of arbaclofen and cians and patients in future management of these diseases.
baclofen was conducted in healthy subjects to compare the plasma and CSF parameters. Twelve subjects in each group received arbaclofen doses of 5, 7.5, or 10mg, or baclofen doses of 20mg every six hours for four days after an up­titration period of Evaluation of authenticity and rationality of promotional
nine days. Subjects completed a drowsiness scale every three pharmaceutical drug literatures
hours while awake on Day 12. Scores ranged from zero “No Chetan B. Yeola1, Gaurav Zope1, Pravita Yadav1, Sachin Upasani1, Drowsiness” to 10 “Worst Possible Drowsiness”. PK samples were Sagar Thakkar1, Manoj Jadhav1, Ashish Nabar2 taken on Day 14. AUC and Cmax values were analyzed by regres­ 1Department of Infectious Diseases, Maharashtra University of sion with the mean daily drowsiness scores.
Health Sciences & Seth G S Medical College and KEM Hospital, Data and Results: No significant correlation was observed
Parel, Mumbai., Parel ( Mumbai), India; 2Department of Cardiology, between drowsiness scores and arbaclofen or baclofen plasma PK Seth G S Medical College and KEM Hospital, Parel, Mumbai., parameters. No significant correlation was found for arbaclofen CSF parameters. However, baclofen CSF AUC and Cmax were significantly correlated to daily drowsiness scores with R2 values Statement of Purpose, Innovation or Hypothesis: The promo­
of 0.78 and 0.88 and p­values of 0.0016 and 0.0001, respectively.
tional activities of pharmaceutical industry are governed by the Interpretation, Conclusion or Significance: These results sug­
World Health Organization, International Federation of Pharma­ gest that drowsiness, the most common dosing­limiting adverse ceutical Manufacturers and Associations, Organization of Phar­ event for baclofen, is associated with CSF exposures of the maceutical Producers of India, which are self regulatory codes. S­enantiomer and not the R­enantiomer.
1354J Clin Pharmacol 2011;51:1326-1369

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