Non-Clinical Pharmacokinetics, Prediction of Human Pharmacokinetics and First-in-Human Dose Selection for CNTO 5825, an Anti-Interleukin-13 Monoclonal Antibody.

Abstract:

:CNTO 5825 is a human anti-interleukin-13 (IL-13) monoclonal antibody (mAb) that inhibits binding of human IL-13 to IL-13Rα1 and IL-13Rα2. The purpose of this investigation was to predict human pharmacokinetics (PK) of CNTO 5825 using different allometric approaches and non-clinical PK data in order to select the right and safe doses for first-in-human (FIH) study. After intravenous (IV) administration of CNTO 5825, clearance (CL) ranged from 9.98 to 11.49 ml/day/kg in rats and from 5.78 to 7.19 ml/day/kg in cynomolgus monkeys. The volume of distribution at steady-state (Vss) in rats was large (151.52-155.64 ml/kg) compared to cynomolgus monkey (49.77-61.10 ml/kg). The terminal half-life (T1/2 ) ranged from 12.29 to 14.15 days in rats and from 6.61 to 7.73 days in cynomolgus monkeys. The PK of CNTO 5825 was linear in 1-10 mg/kg dose range in both species. The bioavailability after subcutaneous (SC) administration was 94% and 79% in rats and cynomolgus monkeys, respectively. The predicted CL and Vss based on allometric methods and PK data from rats and monkeys were within twofold of observed CL and Vss in human beings; the predicted CL and Vss in human beings (70 kg) based on time-invariant method with combined PK data from rats and monkeys were 4.84 ± 1.13 ml/day/kg and 68.93 ± 35.55 ml/kg, respectively. The selected doses for the FIH study based on time-invariant method and no observed adverse effect level in toxicity studies in rats and monkeys provided exposures that were subsequently shown to be well tolerated and safe in human beings.

authors

Nnane IP,Xu Z,Zhou H,Davis HM

doi

10.1111/bcpt.12391

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

219-25

issue

4

eissn

1742-7835

issn

1742-7843

journal_volume

117

pub_type

杂志文章
  • Natural oils affect the human skin integrity and the percutaneous penetration of benzoic acid dose-dependently.

    abstract::Natural oils are extensively used in cosmetics and as treatment for a growing number of more or less specific ailments. Skin irritation and cases of allergy have repeatedly been described in the literature following exposure to these oils. The present study evaluated the extent to which three natural oils (eucalyptus ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2006.pto_388.x

    authors: Nielsen JB

    更新日期:2006-06-01 00:00:00

  • Topical Antimycotics for Oral Candidiasis in Warfarin Users.

    abstract::Treatment for oral candidiasis in warfarin users may be complicated by drug-drug interactions (DDIs) between warfarin and topically applied antimycotics. However, current knowledge of these putative DDIs is merely based on case series. We therefore performed a cohort cross-over study with the objective to evaluate the...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12722

    authors: Hellfritzsch M,Pottegård A,Pedersen AJ,Burghle A,Mouaanaki F,Hallas J,Grove EL,Damkier P

    更新日期:2017-04-01 00:00:00

  • The protective effect of modafinil on vincristine-induced peripheral neuropathy in rats: A possible role for TRPA1 receptors.

    abstract::Vincristine (VCR) induces peripheral neuropathy. We aimed to assess the efficacy of modafinil on VCR-induced neuropathy in rats. Neuropathy was induced by intraperitoneal (i.p.) injections of VCR (0.1 mg/kg). Neuropathic groups received modafinil (5, 25 and 50 mg/kg); gabapentin (20 mg/kg); and a combination of modafi...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.13454

    authors: Amirkhanloo F,Karimi G,Yousefi-Manesh H,Abdollahi A,Roohbakhsh A,Dehpour AR

    更新日期:2020-11-01 00:00:00

  • Red Blood cell IMPDH activity in adults and children with or without azathioprine: Relationship between thiopurine metabolites, ITPA and TPMT activities.

    abstract::Inosine monophosphate dehydrogenase (IMPDH) is considered as the limiting enzyme of thiopurine metabolism for the formation of 6-thioguanine nucleotides (6-TGN). No data are available on the influence of RBC IMPDH activity on the metabolism of thiopurine drugs in individuals with IBD. The aims of this study were as fo...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.13176

    authors: Citterio-Quentin A,El Mahmoudi A,Perret T,Conway A,Ryan A,Beringer A,Lachaux A,Boulieu R

    更新日期:2019-05-01 00:00:00

  • The effect of intraspinal bupivacaine versus levobupivacaine on the QTc intervals during caesarean section: a randomized, double-blind, prospective study.

    abstract::The aim of this study was to describe whether or not spinal anaesthesia with bupivacaine versus levobupivacaine has any effects on the QTc interval during caesarean section. Sixty healthy pregnant women scheduled for elective caesarean section were randomized to spinal anaesthesia with either bupivacaine (the bupivaca...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/bcpt.12146

    authors: Dogan Z,Yildiz H,Akcay A,Coskuner I,Arikan DC,Silay E,Akbudak IH,Kaya H,Oksuz H

    更新日期:2014-03-01 00:00:00

  • Muscarinic receptors in energy homeostasis: Physiology and pharmacology.

    abstract::Despite increased awareness and intensified biomedical research efforts, the prevalence of obesity continues to rise worldwide. This is alarming, because obesity accelerates the progression of several chronic disorders, including type 2 diabetes, cancer and cardiovascular disease. Individuals who experience significan...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审

    doi:10.1111/bcpt.13311

    authors: Falk S,Lund C,Clemmensen C

    更新日期:2020-06-01 00:00:00

  • GSTP1 c.313A>G, XPD c.934G>A, XPF c.2505T>C and CASP9 c.-1339A>G Polymorphisms and Severity of Vomiting in Head and Neck Cancer Patients treated with Cisplatin Chemoradiation.

    abstract::Cisplatin (CDDP) chemotherapy associated with radiation (RT) has been used in advanced head and neck squamous cell carcinoma (HNSCC) patients, and vomiting is a common side effect during treatment. This prospective study aimed to identify the roles of GSTM1 and GSTT1 (presents or nulls), GSTP1 c.313A>G, XPC c.2815A>C,...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12842

    authors: Carron J,Lopes-Aguiar L,Costa EFD,Nogueira GAS,Lima TRP,Pincinato EC,Visacri MB,Quintanilha JCF,Moriel P,Lourenço GJ,Lima CSP

    更新日期:2017-12-01 00:00:00

  • Sinomenine exerts antitumour effect in gastric cancer cells via enhancement of miR-204 expression.

    abstract::Gastric carcinoma (GC) is a pernicious neoplasm with high morbidity and mortality. Sinomenine (SIN) has long been exploited to heal rheumatoid arthritis. Recently, SIN has been discovered to exert the antitumour functions in diverse cancers. However, the impacts of SIN on GC remain indistinct. We attempted to expose t...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,收录出版

    doi:10.1111/bcpt.13285

    authors: Yuan H,Zhang J,Li F,Li W,Wang H

    更新日期:2019-11-01 00:00:00

  • Assessing intrauterine influences on offspring health outcomes: can epidemiological studies yield robust findings?

    abstract::The influence of factors acting during the intrauterine period on health outcomes of offspring is of considerable research and public health interest. There are, however, methodological challenges in establishing robust causal links, because exposures often act many decades before outcomes of interest, may act before ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1742-7843.2007.00191.x

    authors: Smith GD

    更新日期:2008-02-01 00:00:00

  • Icariin inhibits hydrogen peroxide-mediated cytotoxicity by up-regulating sirtuin type 1-dependent catalase and peroxiredoxin.

    abstract::Previous studies suggest that flavonol icariin protects against neuron injury after oxygen and glucose deprivation by increasing SIRT1. This study demonstrates that icariin can inhibit H(2) O(2) -induced neurotoxicity. The neuroprotection of icariin enhances the antioxidant capacity through both a direct scavenging ef...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2010.00595.x

    authors: Zhang L,Huang S,Chen Y,Wang Z,Li E,Xu Y

    更新日期:2010-11-01 00:00:00

  • Possible involvement of oxidative stress in 5-fluorouracil-mediated myelosuppression in mice.

    abstract::Certain chemotherapeutic agents subject cells to oxidative stress, thereby promoting adverse effects. However, the molecular machinery governing 5-fluorouracil (5-FU)-mediated myelotoxicity is obscure. The purpose of this study was to clarify whether 5-FU-induced myelotoxicity is a cause of oxidative stress. Treatment...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2010.00621.x

    authors: Numazawa S,Sugihara K,Miyake S,Tomiyama H,Hida A,Hatsuno M,Yamamoto M,Yoshida T

    更新日期:2011-01-01 00:00:00

  • Interaction between warfarin and cannabis.

    abstract::Delta-9-tetrahydrocannabinol (THC), the main psychoactive cannabinoid in cannabis, may inhibit the cytochrome P450 enzyme CYP2C9. Consequently, cannabis use might infer a risk of drug-drug interaction with substrates for this enzyme, which includes drugs known to have a narrow therapeutic window. In this study, we des...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审

    doi:10.1111/bcpt.13152

    authors: Damkier P,Lassen D,Christensen MMH,Madsen KG,Hellfritzsch M,Pottegård A

    更新日期:2019-01-01 00:00:00

  • Structural insight into Class F receptors - What have we learnt regarding agonist-induced activation?

    abstract::Class F receptors, including the ten Frizzleds (FZD1-10 ) and SMO, mediate the effects of WNTs and hedgehog proteins and belong to the superfamily of G protein-coupled receptors (GPCRs). While the recent, high-resolution insight into mechanisms of GPCR activation provides a better understanding of receptor activation ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审

    doi:10.1111/bcpt.13235

    authors: Schulte G,Kozielewicz P

    更新日期:2020-06-01 00:00:00

  • The pharmacological role of phosphatases (acid and alkaline phosphomonoesterases) in snake venoms related to release of purines - a multitoxin.

    abstract::Snake venom components, acting in concert in the prey, cause their immobilization and initiate digestion. To achieve this, several hydrolytic enzymes of snake venom have evolved to interfere in various physiological processes, which are well defined. However, hydrolytic enzymes such as phosphatases (acid and alkaline ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1742-7843.2010.00630.x

    authors: Dhananjaya BL,D'Souza CJ

    更新日期:2011-02-01 00:00:00

  • Effects of antihypertensive and triglyceride-lowering agents on hepatic copper concentrations in rats with fatty liver disease.

    abstract::Copper deficiency had been suggested to link between fructose-enriched diet (FED) and the development of non-alcoholic fatty liver disease (NAFLD). In this study, we characterized changes in hepatic copper concentrations and hepatic oxidative milieu, in rats with the metabolic syndrome and NAFLD as a result of FED wit...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12283

    authors: Ackerman Z,Skarzinski G,Grozovski M,Oron-Herman M,Sela BA

    更新日期:2014-12-01 00:00:00

  • Geniposide enhances melanogenesis by stem cell factor/c-Kit signalling in norepinephrine-exposed normal human epidermal melanocyte.

    abstract::Geniposide is an iridoid glycoside isolated from the fruit of Gardenia jasminoides Ellis used as a Chinese traditional medicine for treatment of generalized vitiligo. Stem cell factor from keratinocyte recognizes and activates its receptor c-kit carried by melanocyte to potent enhance melanocytic melanogenesis that ca...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2008.00251.x

    authors: Lan WJ,Wang HY,Lan W,Wang KY

    更新日期:2008-07-01 00:00:00

  • Effects of salvianolic acid a on oxidative stress and liver injury induced by carbon tetrachloride in rats.

    abstract::In the present study, we investigated the hepatoprotective effects of salvianolic acid A, a novel antioxidant, against oxidative stress and acute liver injury induced by carbon tetrachloride (CCl(4)) in rats, and the mechanisms underlying its protective effects. Administration of CCl(4) to rats caused severe hepatic d...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7835.2007.00020.x

    authors: Wu ZM,Wen T,Tan YF,Liu Y,Ren F,Wu H

    更新日期:2007-02-01 00:00:00

  • Role of oxidative stress in reproductive toxicity induced by co-administration of chloramphenicol and multivitamin-haematinics complex in rats.

    abstract::Concurrent administration of chloramphenicol (CAP) with multivitamin-haematinics complex (MHC) is a common practice to cushioning anticipated anaemic effect of CAP in most developing countries. This study investigated the mechanism involved in CAP-induced reproductive toxicity as well as the effects of its co-administ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2010.00561.x

    authors: Oyagbemi AA,Adedara IA,Saba AB,Farombi EO

    更新日期:2010-09-01 00:00:00

  • The ABCB1, rs9282564, AG and TT Genotypes and the COMT, rs4680, AA Genotype are Less Frequent in Deceased Patients with Opioid Addiction than in Living Patients with Opioid Addiction.

    abstract::Sudden death due to acute intoxication occurs frequently in patients with opioid addiction (OA). To examine whether certain genotypes were associated with this, we examined the frequencies of 29 SNPs located in candidate genes related to opioid pharmacology: ABCB1, OPRM1, UGT2B7, CYP3A5, CYP2B6, CYP2C19, CYP2D6, COMT,...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12602

    authors: Christoffersen DJ,Damkier P,Feddersen S,Möller S,Thomsen JL,Brasch-Andersen C,Brøsen K

    更新日期:2016-10-01 00:00:00

  • Plasma levels of 25-hydroxyvitamin D3 and in vivo markers of cytochrome P450 3A activity in Swedes and Koreans: effects of a genetic polymorphism and oral contraceptives.

    abstract::In vitro studies have shown that vitamin D may induce several cytochrome P450 (CYP) enzymes in general and CYP3A4 in particular. The primary aim of this study was to investigate the relationship between plasma levels of 25-hydroxyvitamin D3 and suggested in vivo markers of CYP3A activity in healthy volunteers from Swe...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12230

    authors: Nylén H,Björkhem-Bergman L,Ekström L,Roh HK,Bertilsson L,Eliasson E,Lindh JD,Diczfalusy U

    更新日期:2014-10-01 00:00:00

  • Gastrointestinal symptoms as an important sign in premature newborns with severely increased S-digoxin.

    abstract::The aim is to emphasize the importance of extracardiac symptoms of digoxin intoxication in newborns. The most common intoxication symptoms in adults are of cardiac origin, but due to altered symptomatology, digoxin overdose in infants are not always discovered on symptomatic basis. In preterm infants, this is even mor...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2005.pto_09.x

    authors: Nybo M,Damkier P

    更新日期:2005-06-01 00:00:00

  • Anticonvulsant and behavioural effects of the denatured venom of the social wasp Polybia occidentalis (Polistinae, Vespidae).

    abstract::Several investigations demonstrate that neurotoxins isolated from venoms of spiders and wasps may exert specific and selective activity on structures of the mammalian CNS. In the present work we examine the neurological effects of the low molecular weight compounds of the denatured venom of the neotropical social wasp...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2005.pto_137.x

    authors: Mortari MR,Cunha AO,de Oliveira L,Vieira EB,Gelfuso EA,Coutinho-Netto J,Ferreira dos Santos W

    更新日期:2005-11-01 00:00:00

  • Addiction-related effects of DOV 216,303 and cocaine: A comparative study in the mouse.

    abstract::DOV 216,303, an inhibitor of serotonin, noradrenaline and dopamine reuptake, belongs to a new line of drugs called 'triple reuptake inhibitors' that have been proposed for treatment of depression. The addictive drug cocaine has similar mechanism of action and exerts rewarding effects by blocking reuptake of dopamine, ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12182

    authors: Sørensen G,Husum H,Brennum LT,Bundgaard C,Montezinho LC,Mørk A,Wörtwein G,Woldbye DP

    更新日期:2014-06-01 00:00:00

  • Strategies for Using Plagiarism Software in the Screening of Incoming Journal Manuscripts: Recommendations Based on a Recent Literature Survey.

    abstract::In recent years, several online tools have appeared capable of identifying potential plagiarism in science. While such tools may help to maintain or even increase the originality and ethical quality of the scientific literature, no apparent consensus exists among editors on the degree of plagiarism or self-plagiarism ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12568

    authors: Lykkesfeldt J

    更新日期:2016-08-01 00:00:00

  • A latex-induced allergic airway inflammation model in mice.

    abstract::Latex allergy is important due to serious health impacts and widespread use of its products. Latex allergic reactions can be induced in skin and mucosal surfaces including the respiratory tract. The development of murine models of allergic airway inflammation has provided a framework to dissect out the cellular and mo...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2006.pto_530.x

    authors: Farzaneh P,Hassan ZM,Pourpak Z,Hoseini AZ,Hogan SP

    更新日期:2006-12-01 00:00:00

  • A two-way cross-over bioequivalence study comparing two products of diclofenac sodium suppositories in healthy human volunteers.

    abstract::This report presents the results of two treatment cross-over investigations on 20 healthy male volunteers to assess the bioequivalence of two suppository products of diclofenac sodium. The study was carried out under US Food and Drug Administration Guidelines. The two products were voltaren (100 mg) suppository (Ciba-...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 临床试验,杂志文章

    doi:10.1111/j.1742-7843.2004.t01-1-pto950503.x

    authors: Hasan M,Otoom S,Najib N,Sallam el-S

    更新日期:2004-12-01 00:00:00

  • Oxidative DNA damage induced by ethanol in mouse peripheral leucocytes.

    abstract::It is suggested that reactive oxygen species produced during ethanol intake may induce oxidative DNA damage. The present study, by the use of single cell gel electrophoresis (comet assay), investigated the potential genotoxicity of acute and long-term ethanol administration in mouse peripheral leucocytes. Urinary 8-hy...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2008.00258.x

    authors: Guo L,Yang JY,Wu CF

    更新日期:2008-09-01 00:00:00

  • Data mining in spontaneous reports.

    abstract::The increasing size of spontaneous report data sets and the increasing capability for screening such data due to increases in computational power has led to a recent increase in interest and use of data mining on such data. While data mining plays an important role in the analysis of spontaneous reports, there is gene...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1742-7843.2006.pto_232.x

    authors: Bate A,Edwards IR

    更新日期:2006-03-01 00:00:00

  • Different patterns of spinal cyclooxygenase-1 and cyclooxygenase-2 mRNA expression in inflammatory and postoperative pain.

    abstract::Levels of cyclooxygenase-2 (COX-2) mRNA, but not those of COX-1, were reported to be raised significantly after peripheral inflammation in the rat spinal cord. The aim of the present study was to ascertain whether this pattern of COX-2 and COX-1 expression applies also to other pain conditions induced by surgical proc...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2006.pto_457.x

    authors: Prochazkova M,Dolezal T,Sliva J,Krsiak M

    更新日期:2006-08-01 00:00:00

  • Differences in cardiovascular safety with non-steroidal anti-inflammatory drug therapy-A nationwide study in patients with osteoarthritis.

    abstract::Osteoarthritis (OA) and the non-steroidal anti-inflammatory drugs (NSAIDs) used to relieve OA-associated pain have been linked independently to increased cardiovascular risk. We examined the risk of cardiovascular events associated with NSAID use in patients with OA. We employed linked nationwide administrative regist...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.13182

    authors: Barcella CA,Lamberts M,McGettigan P,Fosbøl EL,Lindhardsen J,Torp-Pedersen C,Gislason GH,Olsen AS

    更新日期:2019-05-01 00:00:00