Home About us Contact
|
Home About us Contact | ||
|
|
||
Fixed Dose (fixed + dose)
Selected AbstractsBuprenorphine tapering schedule and illicit opioid useADDICTION, Issue 2 2009Walter Ling ABSTRACT Aims To compare the effects of a short or long taper schedule after buprenorphine stabilization on participant outcomes as measured by opioid-free urine tests at the end of each taper period. Design This multi-site study sponsored by Clinical Trials Network (CTN, a branch of the US National Institute on Drug Abuse) was conducted from 2003 to 2005 to compare two taper conditions (7 days and 28 days). Data were collected at weekly clinic visits to the end of the taper periods, and at 1-month and 3-month post-taper follow-up visits. Setting Eleven out-patient treatment programs in 10 US cities. Intervention Non-blinded dosing with Suboxone® during the 1-month stabilization phase included 3 weeks of flexible dosing as determined appropriate by the study physicians. A fixed dose was required for the final week before beginning the taper phase. Measurements The percentage of participants in each taper group providing urine samples free of illicit opioids at the end of the taper and at follow-up. Findings At the end of the taper, 44% of the 7-day taper group (n = 255) provided opioid-free urine specimens compared to 30% of the 28-day taper group (n = 261; P = 0.0007). There were no differences at the 1-month and 3-month follow-ups (7-day = 18% and 12%; 28-day = 18% and 13%, 1 month and 3 months, respectively). Conclusion For individuals terminating buprenorphine pharmacotherapy for opioid dependence, there appears to be no advantage in prolonging the duration of taper. [source] From heparins to factor Xa inhibitors and beyondEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2005S. Alban Abstract Despite some disadvantages, unfractionated heparin (UFH) and oral anticoagulants have been the only anticoagulants for prophylaxis and therapy of thromboembolic disorders for several decades. Based on the increasing knowledge of the structure and pharmacology of heparin, low molecular weight heparins (LMWH) have been developed in the 1980s. Compared to UFH, their advantages are mainly based on their reduced nonspecific binding to proteins and cells resulting in improved pharmacokinetics. In 1991, LMWH were declared as the most efficient prophylaxis in high-risk patients. Although the use of LMWH is increasing and they are today also applied for therapy and in other indications like acute coronary syndrome, they are considered not optimal concerning efficacy and safety. With the approval of fondaparinux for the prevention of venous thromboembolic disease in high-risk orthopedic patients, there might be a paradigm shift in the field of anticoagulants. Fondaparinux, a synthetic, chemically defined pentasaccharide, is the first selective inhibitor of factor Xa. By its highly specific binding to antithrombin, it selectively inhibits factor Xa and consequently prevents thrombin generation. In contrast to UFH and LMWH, it does not bind to any other cells and other proteins than antithrombin. This leads to a favourable linear pharmacokinetic profile, allowing once-daily subcutaneous application of a fixed dose without monitoring in thromboembolism prophylaxis. In addition to the evaluation of fondaparinux for further indications, chemical modifications of this pentasaccharide such as the long-acting idraparinux are currently under investigation. [source] Appraisal of current vitamin K dosing algorithms for the reversal of over-anticoagulation with warfarin: the need for a more tailored dosing regimenEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2006Elizabeth A. Sconce Abstract:, Warfarin is the most commonly prescribed oral anticoagulant in the UK for the treatment and prevention of thromboembolic disorders. Vitamin K administration is an effective way of reversing excessive anticoagulation. Over-anticoagulated patients present with a wide range of international normalized ratio (INR) values and may respond differently to a fixed dose of vitamin K. Current dosing algorithms for vitamin K administration in the non-urgent treatment of over-anticoagulation do not take this variability in response into account. Consequently, over a third of over-anticoagulated patients still remain outside their target INR 24 h after treatment. Such patients are therefore prone to either haemorrhage (if the patient is still over-anticoagulated) or thromboembolism (if the INR reversal is over-corrected). A number of factors such as patient age, body weight, co-morbidity, frailty, warfarin daily dose and CYP2C9 and VKORC1 polymorphism could affect response to vitamin K and thus the rate and extent of INR reversal. There is a need for a more individualized approach to the reversal of over-anticoagulation in asymptomatic or mildly haemorrhagic patients in order to improve the safety of warfarin therapy. [source] Defining success in clinical trials , profiling pregabalin, the newest AEDEUROPEAN JOURNAL OF NEUROLOGY, Issue 2005P. Ryvlin The efficacy and safety of pregabalin as adjunctive therapy for patients with partial epilepsy with or without secondary generalization has been established by four randomized, 12-week, double-blind, placebo-controlled trials (n = 1396) and four long-term open-label studies (n = 1480). Patients in the three fixed-dose trials were ,12 years of age, had ,6 partial seizures and no 4-week seizure-free period during the 8-week baseline period. Seventy-three per cent of patients were taking ,2 concomitant antiepileptic drugs. Responder rates across the effective doses (150,600 mg/day) ranged from 14% to 51% and demonstrated a significant dose,response relationship. The most common adverse events were central nervous system related, generally mild or moderate, transient, and tended to be dose related. The fourth placebo-controlled trial compared a fixed dose of pregabalin 600 mg/day with a flexible-dose regimen (150,600 mg/day). Responder rates were greater for both the fixed dose (45.3%, P < 0.001) and flexible dose (31.3%, P < 0.001) when compared with placebo (11.0%). Compared with the fixed-dose group, the flexible-dose patients had a lower incidence of adverse events and study discontinuations. In long-term open-label trials, the efficacy of pregabalin was maintained with respect to 50% responder rates suggesting no obvious tolerance developing over 2 years. Seizure-free rates were 8.9% and 5.8% for the last 6 months and 1 year of pregabalin treatment, respectively. Long-term open-label pregabalin treatment was well tolerated. [source] Open-Label Exploration of an Intravenous Nalbuphine and Naloxone Mixture as an Analgesic Agent Following Gynecologic SurgeryPAIN MEDICINE, Issue 6 2007Assaf T. Gordon MD ABSTRACT Objective., The purpose of this series was to explore a 12.5:1 fixed-dose ratio of an intravenous nalbuphine and naloxone mixture (NNM) for use in patients following gynecologic surgery. Design and Patients., Open-label, nonrandomized case series. The first series was a dose-ranging investigation for 12 patients following elective total abdominal hysterectomy or myomectomy. In this series, fentanyl was used for intraoperative analgesia, and patients were assigned to a lower NNM (2.5 mg/0.2 mg) or to a higher NNM (5 mg/0.4 mg) dose group. The second series evaluated the fixed dose of 5 mg nalbuphine/0.4 mg naloxone for four patients undergoing ambulatory gynecologic procedures. In the second series, no opioid agents were administered intraoperatively to eliminate the possibility of mu-opioid reversal by naloxone postoperatively. Outcome Measures., Pain control was assessed using a Verbal Pain Scale (0,10). Vital signs, side effects, and adverse events were recorded to determine drug safety. Results., In the first series, there were no adverse events; however, each patient required rescue medication (either morphine or fentanyl). In the second series, two of the four patients reported a reduction in pain following drug administration and did not require any further analgesic agents in the 3-hour postoperative period. One patient had an asymptomatic lowering of heart rate after receiving the drug. Conclusion., Additional research of the unique combination therapy of nalbuphine and naloxone is warranted to further determine its potential clinical efficacy and safety. [source] Postoperative continuous intrathecal pain treatment in children after selective dorsal rhizotomy with bupivacaine and two different morphine dosesPEDIATRIC ANESTHESIA, Issue 4 2006KARIN HESSELGARD RN Summary Background:, Children undergoing selective dorsal rhizotomy (SDR) experience severe pain postoperatively; a pain related to both the extensive surgical exposure with multilevel laminectomy and nerve root manipulation. We sought to define an optimal dose of continuous intrathecal (IT) morphine and bupivacaine to treat this severe pain. The aim of this study was to compare two different concentrations of morphine in a fixed dose of bupivacaine with regard to the analgesic effect and survey if they differed in side effects. Methods:, Twenty-six children, aged 2.7,7.4 years undergoing SDR were included in this study. Postoperatively 11 children received a continuous infusion of morphine 0.4 ,g.kg,1.h,1 and bupivacaine 40 ,g.kg,1.h,1 (low-dose group) and 15, a continuous infusion of morphine 0.6 ,g.kg,1.h,1 and bupivacaine 40 ,g.kg,1.h,1 (high-dose group). The Behavioral Observational Pain Scale (BOPS) was used to evaluate pain. Results:, Better pain relief was obtained in the high-dose group seen in lower BOPS score compared with the low-dose group [P = 0.03, Fisher's permutation test and P = 0.06 Wilcoxon,Mann,Whitney (WMW) test]. The low-dose group received seven times as much ketobemidone 0.43 ± 0.54 mg.kg,1 48 h,1 compared with 0.06 ± 0.09 mg.kg,1 48 h,1 in the high-dose group (P = 0.0005 Fisher's permutation test, P = 0.0017 WMW test). There was no statistical difference in pruritus and postoperative nausea and vomiting between the groups. Respiratory and hemodynamic depression was not found. Conclusion:, This study shows that, compared with low-dose, the higher dose of continuous IT morphine combined with bupivacaine, significantly reduce pain score and postoperative intravenous analgesic requirements without increasing adverse effects. [source] Prophylaxis of central venous catheter-related thrombosis with minidose warfarin in patients treated with high-dose chemotherapy and peripheral-blood stem-cell transplantation: Retrospective analysis of 228 cancer patientsAMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2006Massimo Magagnoli Abstract Patients with a central venous catheter (CVC) undergoing high-dose chemotherapy (HDC) followed by peripheral-blood stem-cell transplantation (PBSCT) for malignancies are at high risk of thrombosis, but the use of anti-coagulant prophylaxis remains debatable in this setting of patients. We analyzed the efficacy and the safety of minidose warfarin in 228 patients in whom CVCs had been placed and who had received 292 HDC courses of therapy. The catheters remained in place for a mean of 173 (range 40,298) days. All patients received prophylactic oral warfarin in the fixed dose of 1 mg/day starting on the day of CVC insertion. Prophylaxis was interrupted during aplasia when platelet counts fell below 50,000/dL. There were no toxic deaths related to the prophylaxis. Overall there were 4 thrombotic events. Three occurrences were directly related to the catheter, while the remaining event was a deep saphenous-vein thrombosis. A number of potential predictive factors were analyzed for their impact on thrombotic events without finding any significant correlation. Four episodes of bleeding occurred, with each of these individuals having a normal INR but a platelet count below 50,000/dL. Minidose warfarin is effective and safe to use for preventing thrombotic events in this setting of patients. Am. J. Hematol. 81:1,4, 2006. © 2005 Wiley-Liss, Inc. [source] Efficacy of risperidone in the treatment of delirium in elderly patientsPSYCHOGERIATRICS, Issue 2 2008Koji IKEZAWA Abstract Background:, Despite increasing recognition of delirium as a serious complication of physical illness, little has been reported in this area. Interest has been raised in treatment options other than haloperidol, such as atypical antipsychotic agents. Methods:, A 2-week open-label trial of risperidone for the treatment of delirium was conducted to assess the efficacy and tolerance of this medication in elderly patients. Twenty-two patients with DSM-IV-defined delirium were investigated. All patients had the hyperactive,hyperalert variant of delirium. Patients received a fixed dose of risperidone (mean 1.5 ± 0.7 mg; range 0.5,3 mg). Delirium was assessed using the Delirium Rating Scale (DRS) at baseline and on Days 1, 3, 5, 7, and 14 after the initiation of risperidone treatment. Clinical and demographic data, as well as risperidone therapy related information, were collected. Results:, Delirium resolved in all patients over the course of treatment. The mean period over which delirium resolved was 4.0 ± 2.9 days. The mean DRS score at baseline was 20.7 ± 3.0. The DRS score improved from baseline to Day 1 of treatment and continued to improve until the study end-point. Mild side-effects were present in 27.3% of patients. Stepwise logistic regression identified a decrease of 2 points or higher on the DRS on Day 1 associated with side-effects. There were no significant differences in the response to treatment with the different doses of risperidone used. Conclusion:, Our findings indicate that low-dose risperidone (0.5,3.0 mg/day) is effective and safe for the treatment of delirium in elderly patients, and that an early response on Day 1 of treatment may be associated with side-effects in these patients. [source] ORIGINAL ARTICLE: Potency and recovery characteristics of rocuronium mixed with sodium bicarbonateANAESTHESIA, Issue 9 2010H. J. Lee Summary Sodium bicarbonate may be added to rocuronium to decrease pain on injection. However, this mixture may result in the formation of carbon dioxide bubbles. We investigated whether the addition of sodium bicarbonate to rocuronium alters neuromuscular blockade, in 120 patients randomly assigned to receive rocuronium mixed with saline or bicarbonate 8.4%, either in varying doses (for dose-response measurements; 60 patients) or a fixed dose of 600 ,g.kg -1 (for time-course measurements; 60 patients). Sodium bicarbonate resulted in a left-shift of the rocuronium dose-response curve. The effective doses of rocuronium to produce 95% twitch depression were 331.6 (95% CI: 310.4,352.8) and 284.3 (95% CI: 262.0,306.6) ,g.kg,1 mixed with isotonic saline or sodium bicarbonate, respectively (p < 0.001). The mean (SD) onset times of rocuronium 600 ,g.kg -1 were 3.6 (0.6) and 2.7 (0.5) min in the corresponding groups, respectively (p < 0.001). The mean (SD) times to 95% recovery were 35.8 (5.8) and 47.9 (7.1) min, respectively (p < 0.001). We conclude that the mixing of sodium bicarbonate with rocuronium enhances the potency, shortens the onset and prolongs the duration of action. [source] Lamotrigine in the acute treatment of bipolar depression: results of five double-blind, placebo-controlled clinical trialsBIPOLAR DISORDERS, Issue 2 2008Joseph R Calabrese Objectives:, The efficacy of lamotrigine as maintenance treatment for bipolar disorder (BD), particularly for delaying depressive episodes, is well established, but its efficacy in the acute treatment of bipolar depression is less clear. This paper reports the results of five randomized, double-blind, placebo-controlled trials of lamotrigine monotherapy for the acute treatment of bipolar depression. Methods:, Adult subjects with bipolar I or II disorder experiencing a depressive episode were randomized to placebo or lamotrigine monotherapy (after titration, at a fixed dose of 50 mg or 200 mg daily in Study 1; a flexible dose of 100,400 mg daily in Study 2; or a fixed dose of 200 mg daily in Studies 3, 4 and 5) for 7,10 weeks. Results:, Lamotrigine did not differ significantly from placebo on primary efficacy endpoints [17-item Hamilton Depression Rating Scale in Studies 1 and 2; Montgomery,Asberg Depression Rating Scale (MADRS) in Studies 3, 4 and 5]. In Study 1, lamotrigine significantly separated from placebo on some secondary measures of efficacy, including the MADRS, the Clinical Global Impressions-Severity (CGI-S) and the CGI-Improvement (CGI-I), but seldom differed on secondary efficacy endpoints for the other studies. Conclusions:, Lamotrigine monotherapy did not demonstrate efficacy in the acute treatment of bipolar depression in four out of five placebo-controlled clinical studies. Lamotrigine was well tolerated in the acute treatment of bipolar depression. [source] A phase I study of vorinostat in combination with idarubicin in relapsed or refractory leukaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2010Tapan M. Kadia Summary Histone deacetylase inhibitors (HDACi) affect chromatin remodelling and modulate the expression of aberrantly silenced genes. HDACi have single-agent clinical activity in haematological malignancies and have synergistic anti-leukaemia activity when combined with anthracyclines in vitro. We conducted a two-arm, parallel Phase I trial to investigate two schedules of escalating doses of vorinostat (Schedule A: thrice daily (TID) for 14 d; B: TID for 3 d) in combination with a fixed dose of idarubicin in patients with refractory leukaemia. Of the 41 patients enrolled, 90% had acute myeloid leukaemia, with a median of 3 prior therapies. Seven responses (17%) were documented (two complete response (5%), one complete response without platelet recovery (2·5%), and four marrow responses). The 3-d schedule of vorinostat was better tolerated than the 14-d schedule. The maximum tolerated dose for vorinostat was defined as 400 mg TID for 3 d. The most common grade 3 and 4 toxicities included mucositis, fatigue and diarrhoea. Correlative studies demonstrated histone acetylation in patients on therapy and modulation of CDKN1A and TOP2A (topoisomerase II) gene expression. Pharmacokinetic analysis confirmed a dose-related elevation in plasma vorinostat concentrations. The combination of vorinostat and idarubicin is generally tolerable and active in patients with advanced leukaemia and should be studied in the front-line setting. [source] Antioxidants modulate the IL-6 induced inhibition of negative acute-phase protein secretion in HepG2 cellsCELL BIOCHEMISTRY AND FUNCTION, Issue 1 2008Mohamed A. El-Saadany Abstract Despite increasing evidence on the potential of dietary antioxidants in modulating the etiology of certain chronic diseases such as cancer and cardiovascular diseases, little is known about their beneficial role in acute-phase responses and inflammatory diseases. From this viewpoint the aim of this study was to investigate the effect of selected dietary antioxidants in modulating the secretion of negative acute-phase proteins caused by interleukin-6 (IL-6) in HepG2 cells. Cells were first stimulated with a fixed dose of IL-6 for 24,h then incubated for a further 8,h with varying concentrations of eight antioxidants, ,-lipoic acid (LA), (,)-epicatechin (EC), (,)-epicatechin gallate (ECG), (,)-epigallocatechin (EGC), (,)-epigallocatechin gallate (EGCG), ,-tocopherol (TOC), ascorbic acid (AA) and N-acetylcysteine (NAC). The culture supernatants were assayed for transthyretin (TTR) and retinol binding protein (RBP) using ELISA. The data revealed that IL-6 significantly reduced TTR and RBP secretion compared with the basal production. All tested antioxidants attenuate the reduction in TTR and RPB levels. The strongest effects were achieved with the highest concentration of each antioxidant. The order of effect were LA,>,EGCG,>,ECG,>,TOC,>,EGC,>,EC,>,NAC,>,AA. In conclusion, these results provide evidence that the dietary antioxidants can play a fundamental role in inflammatory processes. Copyright © 2007 John Wiley & Sons, Ltd. [source] Early bioavailability of paracetamol after oral or intravenous administrationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2004P. Holmér Pettersson Background:, Paracetamol is a peripherally acting analgesic commonly used in multimodal post-operative pain management to reduce the need for more potent analgesics with their unwanted side-effects. The dose and optimal galenical form for achieving analgesic concentrations is not well defined. The primary aim of this pilot project was to study the early bioavailability for two fixed doses of orally administrated paracetamol and one dose of intravenous propacetamol, all of which were given after minor surgery. Methods:, Thirty-five patients undergoing day surgery were divided into five groups, seven patients each. Groups received either 1 g of an ordinary paracetamol tablet, 2 g of an ordinary paracetamol tablet, 1 g of a bicarbonate paracetamol tablet, 2 g of a bicarbonate paracetamol tablet or 2 g intravenously of prodrug propacetamol. We studied the plasma concentration of paracetamol during the first 80 min after administration. Results:, Within 40 min, intravenous propacetamol gave a median plasma paracetamol concentration of 85 µmol/l (range 65,161) and decreased thereafter. After oral administration, median plasma paracetamol concentration increased with increasing dose and time, but there were huge inter-individual differences at all time points studied. At 80 min after oral paracetamol the median plasma concentrations were 36 and 129 µmol/l for the 1- and 2-g groups, respectively, with an overall range between 0 and 306 µmol/l. Conclusion:, Oral administration of paracetamol as part of multimodal pain management immediately post-operatively resulted in a huge and unpredictable variation in plasma concentration compared with the intravenous administration. [source] Darbepoetin alfa 300 or 500 ,g once every 3 weeks with or without intravenous Iron in patients with chemotherapy-induced anemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2010Michael Auerbach This study evaluated efficacy and safety of darbepoetin alfa administered every 3 weeks (Q3W) at fixed doses of 300 or 500 ,g with or without intravenous (IV) iron in treating anemia in patients receiving multicycle chemotherapy. This Phase 2, double-blind, 2 × 2 factorial study randomized patients to one of four treatment arms; darbepoetin alfa 300 ,g (n = 62), darbepoetin alfa 300 ,g plus IV iron (n = 60), darbepoetin alfa 500 ,g (n = 60), or darbepoetin alfa 500 ,g plus IV iron (n = 60). Patients had nonmyeloid malignancies, hemoglobin levels ,10 g dL,1, and no iron deficiency. Primary endpoint was achievement of target hemoglobin (,11 g dL,1). Secondary endpoints included incidence of transfusions and change in Functional Assessment of Cancer Therapy Fatigue (FACT-F) score from baseline to end of study. Safety was evaluated by incidence of adverse events. No evidence of a statistically significant interaction between darbepoetin alfa dose received and IV iron usage was observed, therefore, results are provided separately comparing darbepoetin alfa doses and comparing IV iron usage groups. Similar proportions of patients receiving darbepoetin alfa 300 or 500 ,g achieved target hemoglobin (75 and 78%, respectively); Kaplan,Meier median time to target hemoglobin was 10 and 8 weeks, respectively. More patients receiving IV iron (82%) than not receiving IV iron (72%) achieved hemoglobin target. Adverse events profiles were similar for darbepoetin alfa treatment groups. Transient anaphylactoid reactions were reported in two patients receiving IV iron. Darbepoetin alfa at 300 ,g Q3W and 500 ,g Q3W showed similar benefit, while added IV iron improved treatment response in these patients. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Can we differentiate the low-molecular-weight heparins?CLINICAL CARDIOLOGY, Issue S1 2000Alexander G.G. Turpie M.B., F.A.C.C., F.A.C.P., F.R.C.P.(LOND., F.R.C.P.C., GLASG.) Abstract The low-molecular-weight heparins (LMWHs) have a number of therapeutic advantages, relative to standard unfractionated heparin (UFH). They are readily bioavailable when injected subcutaneously and can be given in fixed doses, allowing for far simpler administration. Several LMWHs are now commercially available, each demonstrating different physical and chemical properties and different activities in animal models of anticoagulation or hemorrhage. in clinical comparisons with placebo in the treatment of unstable coronary artery disease (UCAD), the LMWHs dal-teparin sodium and nadroparin calcium have demonstrated good anticoagulant efficacy. in comparisons with UFH, on the other hand, only enoxaparin has shown superior anticoagulant activity, as reported in the results of the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) and Thrombolysis in Myocardial Infarction (TIMI) 1 IB trials. However, close scrutiny of the methodology of the clinical trials in UCAD reveals considerable differences in study designs, dosage regimens, duration of administration of active treatments, and the timing and definition of endpoints. Therefore, it would not be scientifically sound to compare results with the different LMWHs based on the current available studies. It is also not possible to draw any conclusions with regard to the relative efficacy of the different LMWHs, since there are no properly-sized comparative data between dal-teparin sodium, enoxaparin sodium, and nadroparin calcium. [source] One-year follow-up of patients with acromegaly treated with fixed or titrated doses of lanreotide Autogel®CLINICAL ENDOCRINOLOGY, Issue 6 2004Ph. Caron Summary objective, Somatostatin analogue treatment is first-line medical therapy for acromegaly. This study compared the efficacy and tolerability of titrated doses of the long-acting somatostatin analogue preparation lanreotide Autogel® with fixed doses and with lanreotide prolonged release (PR) 30 mg microparticles. patients, Patients entering the initial study had received a diagnosis of active acromegaly within the previous 5 years. design, This open, comparative, multicentre study was a 1-year extension of a previous trial during which patients with acromegaly had switched from lanreotide PR 30 mg microparticles injected intramuscularly every 7, 10 or 14 days, for at least 3 months, to one of three fixed doses of lanreotide Autogel® (120, 90, or 60 mg every 28 days, respectively). In this extension study, patients continued to receive 60, 90, or 120 mg of lanreotide Autogel® by deep subcutaneous injection every 28 days for 1 year. Doses could be titrated at entry or after four or eight injections, according to the GH/IGF-I response (dose increased if GH > 2·5 µg/l, or decreased if GH < 1 µg/l with normal IGF-I). measurements, Mean ± SEM GH and IGF-I concentrations were analysed and gallbladder echography performed at weeks 0, 16, 32, and 48. Acromegaly symptoms were recorded monthly and tolerance and side-effects were monitored throughout the study. results, In total, 130 patients entered this extension phase. After 1 year of treatment with titrated doses of lanreotide Autogel®, mean GH (2·4 ± 0·2 µg/l) and IGF-I (287 ± 12 µg/l) concentrations were significantly lower than with lanreotide microparticles (GH, 2·8 ± 0·2 µg/l, P < 0·001; IGF-I, 332 ± 15 µg/l, P < 0·01) or with fixed-dose lanreotide Autogel® (GH, 3·0 ± 0·2 µg/l, P < 0·001; IGF-I, 310 ± 14 µg/l, P = 0·02). GH hypersecretion was reduced to , 2·5 µg/l in 68% of patients with titrated-dose lanreotide Autogel® compared with 49% with microparticles (P < 0·001) and 56% with fixed-dose lanreotide Autogel® (P , 0·005). In the 65 patients who did not require any dose titration, there was no substantial change in serum lanreotide concentration, GH or IGF-I levels over the 12-month study duration. Acromegaly was effectively controlled (GH , 2·5 µg/l and normalized IGF-I) in significantly more patients (43%) compared with microparticles (32%; P < 0·05). There was a trend for improved control of acromegalic symptoms with dose titration, whereas the incidence of gastrointestinal symptoms and local tolerance was similar with lanreotide Autogel® and lanreotide microparticles. Gallbladder echographies showed new lithiasis in 8% of lanreotide Autogel® patients. conclusion, Dose titration of lanreotide Autogel® improved GH and IGF-I control in patients with acromegaly beyond that achieved using fixed doses of lanreotide Autogel® or lanreotide microparticles. Titrated long-term lanreotide Autogel® treatment is well tolerated. [source] | ||||||||||||||||||||||