Interspecies scaling of clearance and volume of distribution for horse antivenom F(ab')2.


:F(ab')2 fragments are sometimes preferred to whole IgG for therapeutic or diagnostic uses. Preclinical pharmaceutical development studies are necessary before their use in humans. Here we propose an allometric approach among three mammalian species to predict F(ab')2 pharmacokinetic parameters in humans. Plasma disposition of horse antivenom F(ab')2 fragments labeled with iodine 125 was studied at a dose of 10 mg/kg i.v. in mice, rats, and rabbits. Using the allometric method, we demonstrate that the pharmacokinetic parameters that correlated with body weight were distribution volume (Vdc (ml) = 0.125 W0.87; Vdss (ml) = 0.251 W0.87; Vd beta (ml) = 0.290 W0.87, r2 = 1), total clearance (Cltot (ml/h) = 0.049 W0.53, r2 = 0.99), and terminal half-life (t1/2 beta (h) = 4.35 W0.33). The F(ab')2 plasma concentration-time data plotted as a complex Dedrick relationship were superimposable. Using these allometric techniques, Vdss, Vd beta, Cltot, and t1/2 beta were calculated as 4.12 liter, 4.78 liter, 19.07 ml/h, and 7.2 days, respectively, for a human subject of 70 kg body wt. Predicted human pharmacokinetic parameters were comparable for volume of distribution with the value reported by Hnatowich et al. (Cancer Res. 47, 6111-6117, 1987): 3.5 liter. However, the clearance was six-fold lower than values given by Hnatowich et al. (130 ml/h) and Ho et al.


Toxicol Appl Pharmacol


Bazin-Redureau M,Pepin S,Hong G,Debray M,Scherrmann JM




Has Abstract


1998-06-01 00:00:00














  • Oxidative stress is involved in Dasatinib-induced apoptosis in rat primary hepatocytes.

    abstract::Dasatinib, a multitargeted inhibitor of BCR-ABL and SRC kinases, exhibits antitumor activity and extends the survival of patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). However, some patients suffer from hepatotoxicity, which occurs through an unkno...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Xue T,Luo P,Zhu H,Zhao Y,Wu H,Gai R,Wu Y,Yang B,Yang X,He Q

    更新日期:2012-06-15 00:00:00

  • Eupafolin inhibits PGE2 production and COX2 expression in LPS-stimulated human dermal fibroblasts by blocking JNK/AP-1 and Nox2/p47(phox) pathway.

    abstract::Eupafolin, a major active component found in the methanol extracts of Phyla nodiflora, has been used to treat inflammation of skin. We examined its effects on cyclooxygenase-2 (COX-2) expression in LPS-treated human dermal fibroblasts. Lipopolysaccharide (LPS) significantly increased prostaglandin-E2 (PGE2) production...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Tsai MH,Lin ZC,Liang CJ,Yen FL,Chiang YC,Lee CW

    更新日期:2014-09-01 00:00:00

  • A compartmental model for the kinetics of mercury vapor in humans.

    abstract::In an earlier study, we exposed nine healthy volunteers to known concentrations of mercury (Hg) vapor in air (median 399; range 365-430 micrograms/m3) for 15 min during light physical exercise (50 W) (Sandborgh-Englund, G., et al., Toxicol. Appl. Pharmacol. 150, 146-153, 1998). Exhaled air, urine, and plasma samples w...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Jonsson F,Sandborgh-Englund G,Johanson G

    更新日期:1999-03-01 00:00:00

  • Computer simulation of the lactational transfer of tetrachloroethylene in rats using a physiologically based model.

    abstract::A physiologically based pharmacokinetic (PBPK) model describing transfer of inhaled tetrachloroethylene (PCE) into breast milk with the consequent exposure of the nursing pups was developed and validated in lactating rats. The PBPK model was based on partition coefficients (PCs), which were determined by the equilibra...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Byczkowski JZ,Kinkead ER,Leahy HF,Randall GM,Fisher JW

    更新日期:1994-04-01 00:00:00

  • A mechanistic study of cigarette smoke and cyclooxygenase-2 on proliferation of gastric cancer cells.

    abstract::Cigarette smoke has been shown to cause gastric cancer. Overexpression of cyclooxygenase-2 (COX-2) is a common characteristic in gastric malignancy. The present study aimed to explore the correlation between cigarette smoke and COX-2 in the promotion of tumorigenesis in human gastric cancer cells (AGS). We further stu...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Shin VY,Liu ES,Ye YN,Koo MW,Chu KM,Cho CH

    更新日期:2004-02-15 00:00:00

  • Benzoquinone inhibits the voltage-dependent induction of the mitochondrial permeability transition caused by redox-cycling naphthoquinones.

    abstract::The mitochondrial permeability pore is subject to regulation by a thiol-dependent voltage sensor (Petronilli, V., Costantini, P., Scorrano, L., Colonna, R., Passamonti, S., and Bernardi, P., J. Biol. Chem. 269, 16638-16642, 1994); thiol oxidation increases the gating potential, which increases the probability of pore ...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Palmeira CM,Wallace KB

    更新日期:1997-04-01 00:00:00

  • MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways.

    abstract::Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Simões MR,Aguado A,Fiorim J,Silveira EA,Azevedo BF,Toscano CM,Zhenyukh O,Briones AM,Alonso MJ,Vassallo DV,Salaices M

    更新日期:2015-03-01 00:00:00

  • Ozone-induced inhibition of theophylline elimination in rabbits: effect of age and sex.

    abstract::The effect of age and sex on the elimination of theophylline in New Zealand White rabbits was investigated following exposure to 0.3 ppm of ozone (O3) for 3.75 hr/day over 5 consecutive days. Animals were given air alone 5 to 7 days before and after the 5 days of O3 exposure. The elimination half-life of theophylline ...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Canada AT,Calabrese EJ

    更新日期:1985-10-01 00:00:00

  • Molecular mechanism of teratogenic effects induced by the fungicide triadimefon: study of the expression of TGF-beta mRNA and TGF-beta and CRABPI proteins during rat in vitro development.

    abstract::Azole derivatives are teratogenic in rats and mice in vitro and in vivo. The postulated mechanism for the dysmorphogenetic effects is the inhibition of retinoic acid (RA)-degrading enzyme CYP26. Azole-related abnormalities are confined to structures controlled by RA, especially the neural crest cells, hindbrain, crani...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Di Renzo F,Corsini E,Broccia ML,Marinovich M,Galli CL,Giavini E,Menegola E

    更新日期:2009-01-01 00:00:00

  • Protection from the toxicity of diisopropylfluorophosphate by adeno-associated virus expressing acetylcholinesterase.

    abstract::Organophosphorus esters (OP) are highly toxic chemicals used as pesticides and nerve agents. Their acute toxicity is attributed to inhibition of acetylcholinesterase (AChE, EC in nerve synapses. Our goal was to find a new therapeutic for protection against OP toxicity. We used a gene therapy vector, adeno-ass...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Li B,Duysen EG,Poluektova LY,Murrin LC,Lockridge O

    更新日期:2006-07-15 00:00:00

  • The surface charge of visible particulate matter predicts biological activation in human bronchial epithelial cells.

    abstract::The physicochemical complexity of airborne particulate matter (PM) has hampered identifying a specific mechanism(s) for its toxicity. In this study, selected physicochemical characteristics (i.e., size, particle number, acidity, and surface charge) were measured on various field PM, derived from urban ambient (St. Lou...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Veronesi B,de Haar C,Lee L,Oortgiesen M

    更新日期:2002-02-01 00:00:00

  • Persistent fibrosis in the liver of choline-deficient and iron-supplemented L-amino acid-defined diet-induced nonalcoholic steatohepatitis rat due to continuing oxidative stress after choline supplementation.

    abstract::Nonalcoholic steatohepatitis (NASH) is characterized by combined pathology of steatosis, lobular inflammation, fibrosis, and hepatocellular degeneration, with systemic symptoms of diabetes or hyperlipidemia, all in the absence of alcohol abuse. Given the therapeutic importance and conflicting findings regarding the po...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Takeuchi-Yorimoto A,Noto T,Yamada A,Miyamae Y,Oishi Y,Matsumoto M

    更新日期:2013-05-01 00:00:00

  • An animal model for the study of chronopharmacokinetics of drugs and application to methotrexate and vinorelbine.

    abstract::An animal model was designed to study the chronopharmacokinetics of intravenous drugs and applied to anticancer agents vinorelbine (VNB) and methotrexate (MTX). Each experiment was performed on four pigs housed in a standardized light-dark cycle (12:12). Four pigs received a 0.16-mg bolus of VNB, followed by a 60-h co...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Prémaud A,Rousseau A,Gicquel M,Ragot S,Manceau J,Laurentie M,Marquet P

    更新日期:2002-09-15 00:00:00

  • The organochlorine o,p'-DDD disrupts the adrenal steroidogenic signaling pathway in rainbow trout (Oncorhynchus mykiss).

    abstract::The mechanisms of action of o,p'-DDD on adrenal steroidogenesis were investigated in vitro in rainbow trout (Oncorhynchus mykiss). Acute exposures to o,p'-DDD inhibited ACTH-stimulated cortisol secretion while cell viability decreased significantly only at the highest concentration tested (200 microM o,p'-DDD). Stimul...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Lacroix M,Hontela A

    更新日期:2003-08-01 00:00:00

  • Studies of inspiratory airflow patterns in the nasal passages of the F344 rat and rhesus monkey using nasal molds: relevance to formaldehyde toxicity.

    abstract::For highly water soluble and reactive gases, such as formaldehyde, the reported distribution of nasal lesions in rats and rhesus monkeys following inhalation exposure may be attributable, at least in part, to regional gas uptake patterns that are a consequence of nasal airflow characteristics. Inspiratory nasal airflo...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Morgan KT,Kimbell JS,Monticello TM,Patra AL,Fleishman A

    更新日期:1991-09-01 00:00:00

  • Activation of the Constitutive Androstane Receptor induces hepatic lipogenesis and regulates Pnpla3 gene expression in a LXR-independent way.

    abstract::The Constitutive Androstane Receptor (CAR, NR1I3) has been newly described as a regulator of energy metabolism. A relevant number of studies using animal models of obesity suggest that CAR activation could be beneficial on the metabolic balance. However, this remains controversial and the underlying mechanisms are sti...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Marmugi A,Lukowicz C,Lasserre F,Montagner A,Polizzi A,Ducheix S,Goron A,Gamet-Payrastre L,Gerbal-Chaloin S,Pascussi JM,Moldes M,Pineau T,Guillou H,Mselli-Lakhal L

    更新日期:2016-07-15 00:00:00

  • Study of the effect of thiols on the vasodilatory potency of S-nitrosothiols by using a modified aortic ring assay.

    abstract::Both low-molecular-mass thiols (LMM-SH) and protein thiols (P-SH) can modulate the biological activity of S-nitrosothiols (RSNO) via S-transnitrosation reactions. It has been difficult to evaluate the entity of this effect in blood circulation by in vitro assays with isolated aorta rings so far, because media rich in ...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Giustarini D,Tsikas D,Rossi R

    更新日期:2011-10-15 00:00:00

  • Initial analyses of the relationship between "Thresholds" of toxicity for individual chemicals and "Interaction Thresholds" for chemical mixtures.

    abstract::The inter-relationship of "Thresholds" between chemical mixtures and their respective component single chemicals was studied using three sets of data and two types of analyses. Two in vitro data sets involve cytotoxicity in human keratinocytes from treatment of metals and a metal mixture [Bae, D.S., Gennings, C., Cart...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章,评审


    authors: Yang RS,Dennison JE

    更新日期:2007-09-01 00:00:00

  • Differential effects of arsenic species on Nrf2 and Bach1 nuclear localization in cultured hepatocytes.

    abstract::Arsenic is a ubiquitous metalloid element present in both inorganic and organic forms in the environment. The liver is considered to be a primary organ of arsenic biotransformation and methylation, as well as the main target of arsenic toxicity. Studies have confirmed that Chang human hepatocytes have an efficient ars...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Liu D,Xu G,Bai C,Gu Y,Wang D,Li B

    更新日期:2021-01-09 00:00:00

  • Determination of myocardium to plasma concentration ratios of five antipsychotic drugs: comparison with their ability to induce arrhythmia and sudden death in clinical practice.

    abstract::Reviewing available data shows that most of antipsychotic drugs are associated with arrhythmia and sudden death. Experimental studies have shown a HERG channel blockade, a dose-dependent increase in duration of action potential or of QT interval, with various degrees of indicators of serious arrhythmogenicity. However...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Titier K,Canal M,Déridet E,Abouelfath A,Gromb S,Molimard M,Moore N

    更新日期:2004-08-15 00:00:00

  • Induction of Fas receptor and Fas ligand by nodularin is mediated by NF-κB in HepG2 cells.

    abstract::Nodularin is a natural toxin with multiple features, including inhibitor of protein phosphatases 1 and 2A as well as tumor initiator and promoter. One unique feature of nodularin is that this chemical is a hepatotoxin. It can accumulate into the liver after contact and lead to severe damage to hepatocyte, such as apop...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Feng G,Li Y,Bai Y

    更新日期:2011-03-15 00:00:00

  • Fumonisin B1 induces protein kinase C translocation via direct interaction with diacylglycerol binding site.

    abstract::Fumonisins are carcinogenic to rats and are suspected human carcinogens. However, the mechanism(s) of carcinogenesis of fumonisn B1 (FB1) is poorly understood. Multiple signal transduction pathways such as protein kinase C (PKC) have been shown to play an important role in carcinogenesis. This study was undertaken to ...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Yeung JM,Wang HY,Prelusky DB

    更新日期:1996-11-01 00:00:00

  • Aryl hydrocarbon receptor-independent activation of estrogen receptor-dependent transcription by 3-methylcholanthrene.

    abstract::Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that stimulates transcription directed by xenobiotic response elements upstream of target genes. Recently, AhR ligands were reported to induce formation of an AhR-estrogen receptor (ER) complex, which can bind to estrogen response elements (ERE...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Shipley JM,Waxman DJ

    更新日期:2006-06-01 00:00:00

  • The accumulations of HIF-1α and HIF-2α by JNK and ERK are involved in biphasic effects induced by different levels of arsenite in human bronchial epithelial cells.

    abstract::The biphasic effects of arsenite, in which low levels of arsenite induce cell proliferation and high levels of arsenite induce DNA damage and apoptosis, apparently contribute to arsenite-induced carcinogenesis. However, the mechanisms underlying this phenomenon are not well understood. In this study, we investigated t...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Xu Y,Li Y,Li H,Pang Y,Zhao Y,Jiang R,Shen L,Zhou J,Wang X,Liu Q

    更新日期:2013-01-15 00:00:00

  • Aromatase inhibition by synthetic lactones and flavonoids in human placental microsomes and breast fibroblasts--a comparative study.

    abstract::Interference of exogenous chemicals with the aromatase enzyme can be useful as a tool to identify chemicals that could act either chemopreventive for hormone-dependent cancer or adverse endocrine disruptive. Aromatase is the key enzyme in the biosynthesis of steroids, as it converts androgens to estrogens. Certain fla...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: van Meeuwen JA,Nijmeijer S,Mutarapat T,Ruchirawat S,de Jong PC,Piersma AH,van den Berg M

    更新日期:2008-05-01 00:00:00

  • Renal necrosis and DNA damage caused by selectively deuterated and methylated analogs of 1,2-dibromo-3-chloropropane in the rat.

    abstract::Selectively deuterated and methylated analogs of the nematocide 1,2-dibromo-3-chloropropane (DBCP) were compared to DBCP in causing acute renal damage in rats. All of the six deuterated analogs tested at 340 mumol/kg, including the perdeutero compound, failed to significantly alter the kidney necrosis observed at 48 h...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Omichinski JG,Brunborg G,Søderlund EJ,Dahl JE,Bausano JA,Holme JA,Nelson SD,Dybing E

    更新日期:1987-12-01 00:00:00

  • Evaluation of an alternative mucosal irritation test using slugs.

    abstract::The objective of this study was to evaluate an alternative mucosal irritation test using the slug Arion lusitanicus as test organism. The effect of 28 reference substances on the mucosal tissue of the slugs was determined by the amount of mucus produced, the reduction in body weight, and the release of proteins from t...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Adriaens E,Remon JP

    更新日期:2002-07-15 00:00:00

  • Physiologically based pharmacokinetic model for methanol in rats, monkeys, and humans.

    abstract::The pharmacokinetics of methanol and formate were characterized in male Fischer-344 rats and rhesus monkeys exposed to methanol vapor concentrations between 50 and 2000 ppm for 6 hr. End-of-exposure blood methanol concentrations were not directly proportional to the atmospheric concentration. The methanol exposures di...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Horton VL,Higuchi MA,Rickert DE

    更新日期:1992-11-01 00:00:00

  • Developmental consequences of in utero sodium arsenate exposure in mice with folate transport deficiencies.

    abstract::Previous studies have demonstrated that mice lacking a functional folate binding protein 2 gene (Folbp2-/-) were significantly more sensitive to in utero arsenic exposure than were the wild-type mice similarly exposed. When these mice were fed a folate-deficient diet, the embryotoxic effect of arsenate was further exa...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Spiegelstein O,Gould A,Wlodarczyk B,Tsie M,Lu X,Le C,Troen A,Selhub J,Piedrahita JA,Salbaum JM,Kappen C,Melnyk S,James J,Finnell RH

    更新日期:2005-02-15 00:00:00

  • Ginsenoside-Rg1 induces angiogenesis by the inverse regulation of MET tyrosine kinase receptor expression through miR-23a.

    abstract::Therapeutic angiogenesis has been implicated in ischemic diseases and wound healing. Ginsenoside-Rg1 (Rg1), one of the most abundant active components of ginseng, has been demonstrated as an angiogenesis-stimulating compound in different models. There is increasing evidence implicating microRNAs (miRNAs), a group of n...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章


    authors: Kwok HH,Chan LS,Poon PY,Yue PY,Wong RN

    更新日期:2015-09-15 00:00:00