Abstract:
BACKGROUND AND OBJECTIVE:A novel tiotropium bromide monodose capsule dry powder inhaler (DPI) formulation and device have been developed. The formulation was based on a spray-dried matrix that enhances the aerosolizaton properties, allowing a less active tiotropium metered dose (13 µg/capsule) while maintaining the same delivered dose (10 µg/actuation). This study describes the pharmacokinetic bioequivalence to the reference product. METHODS:This randomized, two-stage, crossover, semi-replicate (three-way) study was performed in healthy volunteers. In each study period, subjects received a single dose of two capsules (20 μg delivered dose) of the study medication, separated by a 14-day washout period: tiotropium 10 μg delivered dose (Laboratorios Liconsa, Spain) and Spiriva HandiHaler(®) (Boehringer Ingelheim Pharma GmbH & Co KG, Germany). Blood samples were obtained up to 48 h post-dose to evaluate the comparative bioavailability. Tiotropium was measured in plasma by means of dual stage liquid-liquid extraction followed by the two-dimensional ultra-high performance liquid chromatography sensitive sub-pg/mL bioanalytical method. The main pharmacokinetic parameters were maximum plasma concentration (C max), area under the concentration-time curve (AUC) from time zero hours to the last observed concentration at time t (AUC t ), and AUC from time zero hours to 30 min (AUC0.5). Bioequivalence was accepted if the 90.20 % confidence interval (CI) for the ratio test/reference of the primary pharmacokinetic parameters lay within the acceptance range of 80-125 %. Safety assessment was a secondary endpoint. RESULTS:A total of 30 subjects were randomized and bioequivalence was demonstrated for all primary pharmacokinetic parameters: C max (CI 87.26-106.60 %), AUC t (CI 101.33-111.64 %), and AUC0.5 (CI 97.95-113.49 %). Both study treatments were well tolerated (four non-serious adverse events [AEs] were reported in four subjects: one AE before any product administration, two AEs after test product administration; and one AE after reference product administration). CONCLUSIONS:Both products containing tiotropium 10 µg delivered-dose DPI were bioequivalent and showed good tolerability and a similar safety profile.
journal_name
Clin Drug Investigjournal_title
Clinical drug investigationauthors
Algorta J,Andrade L,Medina M,Kirkov V,Arsova S,Li F,Chi Jdoi
10.1007/s40261-016-0441-8subject
Has Abstractpub_date
2016-09-01 00:00:00pages
753-762issue
9eissn
1173-2563issn
1179-1918pii
10.1007/s40261-016-0441-8journal_volume
36pub_type
杂志文章,随机对照试验abstract:BACKGROUND AND OBJECTIVES:Ramucirumab is a fully immunoglobulin G (lgG) monoclonal antibody targeting vascular endothelial growth factor receptor type 2 (VEGFR2). Previous clinical trials suggested ramucirumab could improve the survival and increase the risk of adverse effects. Here, we aimed to assess the efficacy and...
journal_title:Clinical drug investigation
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s40261-015-0355-x
更新日期:2016-01-01 00:00:00
abstract::The superior vena cava (SVC) syndrome occurs when obstruction of this vessel interrupts venous return of blood from the head, upper extremities and thorax to the right atrium. Most cases of SVC syndrome result from neoplasia, especially from lung cancer, but other non-cancer-associated causes may include fibrosis caus...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-200727070-00007
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Hypertension remains a major global health problem, and evidence suggests that the majority of patients will require two or more antihypertensive agents in order to reach specified BP targets. Combining two drugs from different classes has the potential to target different aspects of hypertensi...
journal_title:Clinical drug investigation
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2165/00044011-200929070-00001
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Hypertension, one of the major treatable cardiovascular (CV) risk factors, usually occurs in association with other major risk factors. As well as providing rapid blood pressure (BP) goal attainment, antihypertensive therapy should also provide reductions in CV events and mortality in a wide r...
journal_title:Clinical drug investigation
pub_type: 临床试验,杂志文章,多中心研究
doi:10.2165/00044011-200828110-00001
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:This study was performed in healthy Chinese subjects to evaluate the safety and pharmacokinetic/pharmacodynamic characteristics of a novel injection formulation of dexlansoprazole in the context of single and multiple administration, compared with the original lansoprazole injection. METHODS:H...
journal_title:Clinical drug investigation
pub_type: 临床试验,杂志文章
doi:10.1007/s40261-019-00824-2
更新日期:2019-10-01 00:00:00
abstract::Mecapegfilgrastim (HHPG-19K) is a long-acting pegylated recombinant human granulocyte-colony stimulating factor (rhG-CSF) that is administered subcutaneously as prophylaxis once per chemotherapy cycle as a weight-adjusted dose of 100 µg/kg or as a 6 mg fixed dose. It is approved in China to reduce the incidence of inf...
journal_title:Clinical drug investigation
pub_type: 杂志文章,评审
doi:10.1007/s40261-019-00836-y
更新日期:2019-10-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Dobutamine causes an increase in cardiac output (CO) by augmenting stroke volume (SV) through enhanced left ventricular contractility and by decreasing systemic vascular resistance. However, in some patients, the dominant mechanism by which dobutamine improves left ventricular performance is an...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.2165/00044011-200828020-00006
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Gemigliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor used in the treatment of type 2 diabetes mellitus. This study evaluated possible pharmacodynamic and pharmacokinetic interactions between gemigliptin and metformin and investigated their tolerability. METHODS:A randomized, open-la...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40261-014-0184-3
更新日期:2014-06-01 00:00:00
abstract:BACKGROUND:Oral contraceptives (OCs) are one of the most commonly used classes of drugs worldwide. A case of neutropenia and associated infections in a young woman using OCs that settled after discontinuation and reappeared upon re-challenge, has led us to investigate a potential association between oral contraceptives...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-019-00818-0
更新日期:2019-10-01 00:00:00
abstract:OBJECTIVES:This study investigated the pharmacokinetics and pharmacodynamics of a fixed-dose combination (FDC) tablet of olmesartan medoxomil 20 mg and amlodipine 5 mg (CS-8663) in healthy Chinese subjects. METHODS:This single-centre, open-label study was conducted in five healthy males and five females aged 18-45 yea...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-012-0026-0
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Pegylated interferon (peg-IFN)-α2a and -α2b show different pharmacokinetic properties but are used interchangeably for hepatitis C treatment in traditional dual combinations and with newer agents. We assessed whether peg-IFN antiviral effects vary with peg-IFN subtype, affecting viral response...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-014-0241-y
更新日期:2014-12-01 00:00:00
abstract::Intramuscular 17 α-hydroxyprogesterone caproate (Makena(®)), a synthetic progestin, is indicated to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of a singleton spontaneous preterm birth. Makena(®) reduces the risk of preterm birth in this patient population, and is associated...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-013-0060-6
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Olanzapine is an atypical antipsychotic indicated for the treatment of schizophrenia and, either as monotherapy or as an adjunct to lithium or valproate, for bipolar I disorder. Multiple daily doses of olanzapine do not affect the pharmacokinetics of lithium or valproate; therefore, concomitant...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-019-00860-y
更新日期:2020-01-01 00:00:00
abstract::Cefoperazone is a third-generation cefalosporin that contains the N-methyl- thio-tetrazole (NMTT) side chain, which inhibits vitamin K-dependent carboxylation. Administration of NMTT-containing cefalosporins can cause alterations in the hepatic glutathione redox state, resulting in a dose-related increase in oxidised ...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-200626080-00006
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVE:To compare the efficacy and safety of single doses of quinfamide and secnidazole in the treatment of amoebic non-dysenteric colitis in children. DESIGN:This was a prospective, longitudinal, double-blind, randomised, comparative study. SETTING:The participants were students or relatives of students at two ur...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-200020020-00003
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Characteristics of nucleoside reverse transcriptase inhibitors (NRTIs) make the drug class susceptible to elimination via continuous veno-venous hemofiltration (CVVH), potentially leading to suboptimal drug concentrations if given at the recommended anephric doses during CVVH. The objective of ...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-015-0275-9
更新日期:2015-04-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:The hematological side effects associated with mycophenolic acid (MPA) are relatively common and have severe consequences. The majority of literature data have not shown clear consistency in the MPA exposure-neutropenia relationship. We hypothesized that (i) adult de novo kidney transplant rec...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-018-0694-5
更新日期:2018-11-01 00:00:00
abstract::Currently three different inactivated influenza vaccine types are available: whole virus (WV), split (SPL) and subunit (SU) vaccines. Physicians and patients at risk for influenza complications may wonder whether there are important differences between the vaccine types with respect to antibody induction (serology) an...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-199815010-00001
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:CKD-712, a candidate treatment for septic shock, acts by increasing cardiac output. This study investigated changes in the pharmacodynamics, pharmacokinetics, and tolerability of CKD-712 after a single intravenous administration. METHODS:A dose-block-randomized, double-blind, placebo-controll...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40261-017-0494-3
更新日期:2017-04-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Status epilepticus (SE) is an important emergency situation associated with high morbidity and mortality. The goal of pharmacological therapy-rapid seizure termination-is only achieved in just over half of patients with first-line anti-epileptic drug (AED) therapy and many patients require sec...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-015-0295-5
更新日期:2015-07-01 00:00:00
abstract:BACKGROUND:Multimodal pain therapy including cyclo-oxygenase-2 inhibitors can result in optimal pain management with decreased opioid use and fewer opioid-related adverse events. Patient reported outcomes (PROs) help identify benefits in reduced opioid use and increased pain control. METHODS:In this randomized, double...
journal_title:Clinical drug investigation
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2165/11317570-000000000-00000
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β2-adrenoceptor agonist that has been approved in the EU for the treatment of chronic obstructive pulmonary disease (COPD). Ethnic differences may influence the pharmacokinetics and pharmacodynamics of a drug, and it is therefore important to com...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.2165/11586520-000000000-00000
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Golimumab is a fully human anti-tumor necrosis factor monoclonal antibody approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). This study estimated rates of prespecified outcomes in patients with RA, PsA or AS initiating golimumab ...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-020-00959-7
更新日期:2020-11-01 00:00:00
abstract::Heart rate is an established prognostic marker for longevity and is an important contributor in the pathophysiology of various cardiovascular diseases, including ischemic heart disease and heart failure. Most ischemic episodes are triggered by an increase in heart rate, which causes an imbalance between myocardial oxy...
journal_title:Clinical drug investigation
pub_type: 杂志文章,评审
doi:10.1007/s40261-016-0472-1
更新日期:2017-02-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Oxycodone tamper resistant (OTR) is a new extended-release abuse-deterrent formulation providing improvements in the tamper resistant characteristics. This study aimed to investigate the pharmacokinetic properties of the new OTR tablets and evaluate the bioequivalence of oxycodone from OTR and...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40261-019-00870-w
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Nonsteroidal anti-inflammatory drugs are effective analgesics but their use during tonsillectomy is controversial because of the risk of postoperative bleeding. The aim of this study was to compare the analgesic efficacy and safety of nimesulide, a preferential cyclo-oxygenase type-2 inhibitor,...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-200323100-00004
更新日期:2003-01-01 00:00:00
abstract:OBJECTIVE:To compare the bioavailability of two 15mg ambroxol lozenges with a commercial 30mg ambroxol tablet. DESIGN:Open-label, two-way crossover study. METHOD:Each formulation was randomly administered to 20 healthy Thai volunteers (ten male and ten female) with a 1-week washout period between formulations. After ...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-200323040-00007
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:The enigmatic etiology of neurodegenerative diseases poses a challenge for the development of novel and efficient drugs. The objective of the present study was to evaluate the efficacy of a polyherbal (test) formulation on cognitive functions, inflammatory markers and oxidative stress in health...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40261-014-0235-9
更新日期:2014-12-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Insulin degludec is a basal insulin with a slow and distinct absorption mechanism resulting in an ultra-long, flat, and stable pharmacokinetic profile in patients with diabetes mellitus. The aim of this study was to examine the effect of hepatic impairment on the single-dose pharmacokinetics of...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-013-0154-1
更新日期:2014-02-01 00:00:00
abstract:BACKGROUND:Urinary tract infection (UTI) is a leading cause of morbidity in the female population, with high levels of prevalence and recurrence within 6 months. OBJECTIVES:Our objective was to estimate annual costs and health resource utilization by women with UTIs, and the impact on quality of life (QoL) due to lowe...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-013-0069-x
更新日期:2013-04-01 00:00:00