Abstract:
AIMS:BG00010 is a protein in the glial cell line-derived neurotrophic factor (GDNF) family. It is a selective ligand for the GDNF family receptor alpha-3 (GFRα3) co-receptor that normalizes cellular changes resulting from damage or disease, and potentially alleviates neuropathic pain. The main objectives of this study were to evaluate the pharmacokinetic and safety profiles and to determine the effects on pain of ascending doses of intravenous injections of BG00010 in patients with sciatica. METHODS:This was a randomized, blinded, placebo-controlled multiple-dose study in subjects with sciatica. In Part I (16 patients), four IV dose levels were examined (50, 150, 400, 800 μg kg(-1) ) and in Part II (12 patients), three dose levels were examined (400, 600 and 1200 μg kg(-1) ). Safety and efficacy assessments were used as endpoints. RESULTS:The BG00010 concentration-time data indicated relatively low inter-patient variability and there was a dose-dependent (not dose-proportional) increase in serum exposure from 150 to 1200 μg kg(-1) . The effective half-life was between 40 and 60 h. The most frequently occurring adverse events (AEs) reported by patients receiving BG00010 were headache (67-83%), feeling hot (50-100%), and pruritus (42-67%). Most AEs were mild; no serious AEs or AEs leading to discontinuation occurred. Higher dose regimens of BG00010 resulted in greater pain reduction than placebo or lower dose regimens, although a clear dose-response relationship was not seen. CONCLUSIONS:The pharmacokinetic profile of BG00010 was characterized by low intra-patient variability. These data from a small sample suggest that BG00010 may have a benefit for patients with sciatica.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Okkerse P,Hay JL,Versage E,Tang Y,Galluppi G,Ravina B,Verma A,Williams L,Aycardi E,Groeneveld GJdoi
10.1111/bcp.12941subject
Has Abstractpub_date
2016-07-01 00:00:00pages
108-17issue
1eissn
0306-5251issn
1365-2125journal_volume
82pub_type
杂志文章,随机对照试验abstract::1. Recent work has demonstrated artificial penile erection after intracavernous injection of prostaglandin E1 (PGE1). A possible dose-response relationship between PGE1 and its erectile action was examined in a double-blind, cross-over designed, placebo-controlled study. 2. Twenty patients aged (mean +/- s.d.) 45 +/- ...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1989.tb03543.x
更新日期:1989-11-01 00:00:00
abstract::Although blood pressure measured at the brachial artery plays a central role in our understanding and management of cardiovascular risk, in recent years great emphasis has been placed on the importance of central blood pressure. It seems straightforward that knowledge of the blood pressure directly affecting the major...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2012.04203.x
更新日期:2012-08-01 00:00:00
abstract::1 We have given fifteen healthy volunteers single doses of racemic (+/-)-propranolol orally (40 mg) and intravenously (5-10 mg) to find out how large the variation was of the ratio between (-)- and (+)-propranolol plasma levels in relation to that of total levels of propranolol and 4-hydroxypropranolol. 2 Total propra...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb04937.x
更新日期:1982-07-01 00:00:00
abstract::1 Forty-one patients with essential hypertension, stages I, II, and III, were treated with captopril alone or in combination with hydrochlorothiazide. Forty two percent were responsive to captopril alone, while the remaining 58% also required the diuretic. The need for the diuretic was related to the phase of hyperten...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb02065.x
更新日期:1982-01-01 00:00:00
abstract::Six patients received 10 mg of midazolam intravenously during the anhepatic period of liver transplantation. Arterial blood was sampled during this time and for a similar period following revascularisation. The plasma was analysed using gas chromatography and electron capture detection (GC-ECD) for midazolam alpha-hyd...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1989.tb03429.x
更新日期:1989-05-01 00:00:00
abstract::Caffeine (5 mg kg-1) was administered orally to two healthy, non-smoking subjects on three separate occasions--before, and during therapy with the xanthine oxidase inhibitor allopurinol at doses of either 300 or 600 mg daily. Plasma and urinary levels of methylxanthines, endogenous oxypurines and allopurinol and its m...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1986.tb05222.x
更新日期:1986-04-01 00:00:00
abstract::1 In healthy male volunteers dazoxiben (UK 37248), an inhibitor of thromboxane synthetase, abolished the arterial and venous vasoconstriction produced in the forearm by cold stimulation. 2 Aspirin alone had no effect on this vasoconstriction but negated the effect of dazoxiben. 3 In vitro dazoxiben increased the produ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb02118.x
更新日期:1983-01-01 00:00:00
abstract::1. Double-blind controlled comparisons of nomifensine with placebo, imipramine, desipramine, viloxazine, nortriptyline, a combination of amitriptyline and chlordiazepoxide, and diazepam have been carried out in various parts of the world. 2. Dosage ranged from 50-225 mg daily, and treatment lasted from 2-26 weeks. 3. ...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,评审
doi:10.1111/j.1365-2125.1977.tb05759.x
更新日期:1977-01-01 00:00:00
abstract::1. The dose-related effects of azapropazone on (i) event-related and spontaneous EEG-activity and (ii) the subjects' pain ratings were investigated using an experimental human pain model based on both chemo-somatosensory event-related potentials (CSSERP) and subjects' pain ratings. 2. Healthy subjects (n = 20) partici...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1995.tb05799.x
更新日期:1995-12-01 00:00:00
abstract::1. The primary aim of this study was to assess the impact of renal haemodynamics on the pharmacokinetic behaviour of ibuprofen enantiomers. Thirty-two patients and ten age-matched healthy volunteers participated in this study. These patients had at least one of the following risk factors for cardiovascular disorders: ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1995.tb04536.x
更新日期:1995-07-01 00:00:00
abstract:AIMS:To study the pharmacokinetics and bioavailability of the prodrug bambuterol and its bronchodilator moiety terbutaline in healthy subjects. METHODS:Eight healthy subjects (four women) received intravenous doses of bambuterol and terbutaline. On a third occasion, they, plus another four subjects, ingested oral bamb...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2125.1998.00695.x
更新日期:1998-05-01 00:00:00
abstract::The hypertensive disorders of pregnancy (HDP) are a leading cause of maternal mortality and morbidity in both well and under-resourced settings. Maternal, fetal, and neonatal complications of the HDP are concentrated among, but not limited to, women with pre-eclampsia. Pre-eclampsia is a systemic disorder of endotheli...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2011.04002.x
更新日期:2011-09-01 00:00:00
abstract:AIMS:The aim of the present study was to evaluate the disposition of metoprolol after oral administration of an immediate and controlled-release formulation before and after Roux-en-Y gastric bypass (RYGB) surgery in the same individuals and to validate a physiologically based pharmacokinetic (PBPK) model for predictin...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/bcp.12666
更新日期:2015-11-01 00:00:00
abstract::1. The pharmacokinetics, bioavailability and metabolism of nitrendipine were studied in six healthy volunteers (three females, three males) using [13C4]-nitrendipine as a biological internal standard. In the first study the drug was administered simultaneously by the i.v. [13C4] and p.o. (solution) routes and in a sec...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1987.tb03214.x
更新日期:1987-11-01 00:00:00
abstract::The metabolism of morphine was studied in seven fullterm neonates and five infants receiving a continuous infusion of morphine. All the patients had detectable plasma concentrations of morphine 3-glucuronide (M3G) and 10 had detectable concentrations of morphine 6-glucuronide (M6G). The mean plasma clearance of morphi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1992.tb05652.x
更新日期:1992-11-01 00:00:00
abstract:AIMS:Roux-en-Y gastric bypass (RYGB) alters the anatomical structure of the gastrointestinal tract, which can result in alterations in drug disposition. The aim of the present study was to evaluate the oral disposition of two compounds belonging to the Biopharmaceutical Classification System Class II - fenofibrate (bil...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/bcp.13054
更新日期:2016-11-01 00:00:00
abstract::1. The dose-peak effect relationship of lisinopril was evaluated in a double-blind, parallel study in 83 patients with mild to moderate essential hypertension (supine diastolic blood pressure = 95-115 mm Hg). 2. After a 4 week placebo washout, patients were randomly assigned to one of four treatments: lisinopril 2.5, ...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1988.tb03342.x
更新日期:1988-05-01 00:00:00
abstract::1. Ten healthy subjects received two treatments: a single 1 g oral dose of nalidixic acid (NA) followed 1 h later by either an infinitesimal dilution of the drug (NA 7CH) or by succussed water which served as placebo. The study was repeated 18 months later in 10 different subjects. 2. A further 10 healthy subjects rec...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1991.tb05610.x
更新日期:1991-07-01 00:00:00
abstract:AIMS:To study the impact of risperidone (RISP) on clozapine (CLZ) biotransformation in vitro in microsomal fractions containing varying expression of CYP oxidases and in vivo in patients. METHODS:Human liver microsomes (n= 11) were assessed for expression of CYPs 1A2, 2D6 and 3A4, because these enzymes mediate RISP an...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2125.2009.03476.x
更新日期:2009-10-01 00:00:00
abstract::1. Studies using human liver microsomes and six recombinant human CYP isoforms (i.e. CYP1A2, 2A6, 2B6, 2D6, 2E1 and 3A4) were performed to identify the cytochrome P450 (CYP) isoform(s) involved in the ring 4-hydroxylation and side-chain N-desisopropylation of propranolol enantiomers in humans. 2. alpha-Naphthoflavone ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1995.tb04472.x
更新日期:1995-04-01 00:00:00
abstract:AIMS:Statins have been suggested to prevent haematological malignancies. Several epidemiological studies have evaluated this association, while randomized controlled trials (RCTs) on cardiovascular outcomes have provided relevant data as secondary end-points. Our aim was to examine the strength of this association thro...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1111/j.1365-2125.2007.02959.x
更新日期:2007-09-01 00:00:00
abstract::A free lignocaine index was developed on the basis of measurements of plasma lignocaine and its principle binding protein, alpha 1-acid glycoprotein (AAG) in 80 samples from 16 patients admitted to the coronary care unit and given prophylactic lignocaine therapy. The free drug fraction, fu, of lignocaine was determine...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb05132.x
更新日期:1985-12-01 00:00:00
abstract::1. The relative bioavailability of cyclosporin was studied in 11 healthy volunteers after single oral capsule doses of cyclosporin on three separate occasions; fasting, with breakfast and with breakfast together with bile acid tablets (400 mg of cholic acid and 100 mg of dehydrocholic acid). 2. There was a significant...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb03677.x
更新日期:1990-05-01 00:00:00
abstract::Eleven patients with stable rheumatoid disease (RD) who were receiving regular corticosteroid therapy (CS) were investigated to discover the effect on plasma prednisolone levels of additional therapy with the non-steroidal anti-inflammatory (NSAI) drugs, indomethacin and naproxen. There was a highly significant (P les...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb02010.x
更新日期:1982-09-01 00:00:00
abstract::The effects of single oral doses of atenolol 50 mg and xamoterol 200 mg (a recently developed partial beta 1-adrenoceptor agonist) on lung function, heart rate and blood pressure were investigated in 11 patients with asthma. Xamoterol caused a significant increase in heart rate and systolic blood pressure, which chang...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1986.tb02940.x
更新日期:1986-11-01 00:00:00
abstract::In many endoscopy units midazolam is replacing diazepam as the intravenous sedative of first choice. Midazolam is approximately twice as potent as diazepam. Although generally considered a safe drug, there have been a number of recent reports, particularly in the elderly, of the drug causing hypotension, respiratory d...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1987.tb03037.x
更新日期:1987-02-01 00:00:00
abstract:AIMS:Previous in vivo studies with sumatriptan, a 5HT1-receptor agonist, have demonstrated vasopressor responses in the pulmonary and systemic arterial circulation. Pulmonary artery wedge pressure (PAWP) also increases after sumatriptan injection, raising the possibility of an additional venoconstrictive action or a ne...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1997.00555.x
更新日期:1997-03-01 00:00:00
abstract:AIMS:The aim was to assess the impact of a campaign for general practitioners (GPs) to reduce clinically-important drug-drug interactions (DDIs) in poly-treated elderly patients. METHODS:We compiled a list of 53 DDIs and analyzed reimbursed prescriptions dispensed to poly-treated (≥four drugs) elderly (>65 years) pati...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12754
更新日期:2015-12-01 00:00:00
abstract::1. In nine patients with essential hypertension, following single and multiple doses of ketanserin, assessments were made of blood pressure and heart rate, QT interval, and pressor responses to phenylephrine and angiotensin II. 2. Significant reductions in blood pressure occurred for 6 h after the first dose, on avera...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1987.tb03218.x
更新日期:1987-11-01 00:00:00
abstract::Three hypothalamic regulatory hormones, thyrotrophin-releasing hormone (TRH), luteinizing hormone/follicle-stimulating hormone-releasing hormone (LH/FSH-RH) and growth hormone-release inhibiting hormone (GH-RIH) given intravenously had no effect on the electroencephalographic response known as the contingent negative ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1976.tb04871.x
更新日期:1976-08-01 00:00:00