abstract：:Universally present but overlooked cavities or pockets in long-lived biopharmaceuticals, such as monoclonal antibodies (mAbs), are capable of binding small drugs. Such direct interactions can alter the pharmacokinetics of drugs and potentially affect clinical outcome. The extreme differences in the pharmacokinetic pro...

journal_title：Journal of clinical pharmacology

authors： Panayotatos N

更新日期：2008-10-01 00:00:00

abstract：:Abetimus sodium is an oligonucleotide-based investigational drug designed to treat patients with lupus nephritis by specifically reducing anti-double-stranded DNA antibody levels. The safety and pharmacokinetics of abetimus were evaluated in 24 healthy volunteers at intravenous doses of 600 mg, 1200 mg, and 2400 mg. T...

journal_title：Journal of clinical pharmacology

authors： Linnik MD,O'Rourke AM,Crowther MA

更新日期：2008-08-01 00:00:00

abstract：:Taranabant is a cannabinoid-1 receptor inverse agonist for the treatment of obesity. This study evaluated the safety, pharmacokinetics, and pharmacodynamics of taranabant (5, 7.5, 10, or 25 mg once daily for 14 days) in 60 healthy male subjects. Taranabant was rapidly absorbed, with a median t(max) of 1.0 to 2.0 hours...

journal_title：Journal of clinical pharmacology

authors： Addy C,Rothenberg P,Li S,Majumdar A,Agrawal N,Li H,Zhong L,Yuan J,Maes A,Dunbar S,Cote J,Rosko K,Van Dyck K,De Lepeleire I,de Hoon J,Van Hecken A,Depré M,Knops A,Gottesdiener K,Stoch A,Wagner J

更新日期：2008-06-01 00:00:00

abstract：:Propiverine extended release is expected to be better tolerated compared to immediate release tablets because of slower drug release and reduced formation of active metabolites in the colon. CYP3A4 and ABCC2, the major variables in pharmacokinetics of propiverine, are less expressed in the colon. Therefore, dispositio...

journal_title：Journal of clinical pharmacology

authors： May K,Westphal K,Giessmann T,Wegner D,Adam U,Lerch MM,Oertel R,Warzok RW,Weitschies W,Braeter M,Siegmund W

更新日期：2008-05-01 00:00:00

abstract：:A total of 71 HIV-negative healthy adults were randomized to 1 of 6 regimens to receive lopinavir/ritonavir tablets 400/100 mg twice daily (bid) or 800/200 mg once daily (qd) or atazanavir 300 mg + ritonavir 100 mg qd from study days 1 to 15 with a moderate-fat meal. One hour before breakfast, either omeprazole 40 mg ...

journal_title：Journal of clinical pharmacology

authors： Klein CE,Chiu YL,Cai Y,Beck K,King KR,Causemaker SJ,Doan T,Esslinger HU,Podsadecki TJ,Hanna GJ

更新日期：2008-05-01 00:00:00

abstract：:Taranabant is a novel cannabinoid CB-1 receptor (CB1R) inverse agonist in clinical development for the treatment of obesity. This double-blind, randomized, placebo-controlled, single oral dose study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of taranabant (0.5-600 mg) in 24 healthy male...

journal_title：Journal of clinical pharmacology

authors： Addy C,Li S,Agrawal N,Stone J,Majumdar A,Zhong L,Li H,Yuan J,Maes A,Rothenberg P,Cote J,Rosko K,Cummings C,Warrington S,Boyce M,Gottesdiener K,Stoch A,Wagner J

更新日期：2008-04-01 00:00:00

abstract：:Traditionally, plasma or serum drug concentrations have been used for the assessment of bioavailability and bioequivalence. Since in the majority of cases the site of drug action is in the tissue rather than the blood, the use of corresponding free, unbound concentrations in the tissue is a much more meaningful approa...

journal_title：Journal of clinical pharmacology

authors： Schmidt S,Banks R,Kumar V,Rand KH,Derendorf H

更新日期：2008-03-01 00:00:00

abstract：:Raltegravir is a novel HIV-1 integrase inhibitor with potent in vitro activity (95% inhibitory concentration = 33 nM in 50% human serum). In vitro characterization of raltegravir inhibition potential was assessed against a panel of cytochrome P450 (CYP) enzymes. An open-label, 2-period study was conducted to assess th...

journal_title：Journal of clinical pharmacology

authors： Iwamoto M,Kassahun K,Troyer MD,Hanley WD,Lu P,Rhoton A,Petry AS,Ghosh K,Mangin E,DeNoia EP,Wenning LA,Stone JA,Gottesdiener KM,Wagner JA

更新日期：2008-02-01 00:00:00

abstract：:To study the pharmacokinetics of single increasing intravenous doses (40-160 mg) and repeated doses (80 mg for 7 days) of lecithinized superoxide dismutase (PC-SOD) in Japanese volunteers and to compare the pharmacokinetics of PC-SOD between Caucasians and Japanese. The Japanese study consisted of 2 parts: a single-do...

journal_title：Journal of clinical pharmacology

authors： Suzuki J,Broeyer F,Cohen A,Takebe M,Burggraaf J,Mizushima Y

更新日期：2008-02-01 00:00:00

abstract：:This study investigated the steady-state pharmacokinetic interaction between the HIV protease inhibitor, darunavir (TMC114), administered with low-dose ritonavir (darunavir/ritonavir), and clarithromycin in HIV-negative healthy volunteers. In a 3-way crossover study, 18 individuals received darunavir/ritonavir 400/100...

journal_title：Journal of clinical pharmacology

authors： Sekar VJ,Spinosa-Guzman S,De Paepe E,De Pauw M,Vangeneugden T,Lefebvre E,Hoetelmans RM

更新日期：2008-01-01 00:00:00

abstract：:The medication history among hospitalized patients often relies on patients' self-reports due to insufficient communication between health care professionals. The aim of the present study was to estimate the reliability of patients' self-reported medication use. Five hundred patients admitted to an acute medical depar...

journal_title：Journal of clinical pharmacology

authors： Glintborg B,Hillestrøm PR,Olsen LH,Dalhoff KP,Poulsen HE

更新日期：2007-11-01 00:00:00

abstract：:A randomized, dose-escalating study evaluated the pharmacokinetics of single and multiple oral doses of pirfenidone, a promising antifibrotic agent, in 48 healthy Chinese volunteers. The effects of sex and food on the pharmacokinetics of pirfenidone were also evaluated. Pharmacokinetics was determined from serial bloo...

journal_title：Journal of clinical pharmacology

authors： Shi S,Wu J,Chen H,Chen H,Wu J,Zeng F

更新日期：2007-10-01 00:00:00

abstract：:The safety, tolerability, and pharmacokinetics of orally administered enzastaurin were evaluated in 2 placebo-controlled, dose escalation studies in healthy subjects. In the first human dose study, single doses (2-400 mg) were evaluated, with 22 subjects receiving enzastaurin. The mean half-lives of enzastaurin and it...

journal_title：Journal of clinical pharmacology

authors： Welch PA,Sinha VP,Cleverly AL,Darstein C,Flanagan SD,Musib LC

更新日期：2007-09-01 00:00:00

abstract：:Vildagliptin is a potent and selective dipeptidyl peptidase IV inhibitor in development for the treatment of type 2 diabetes that improves glycemic control by enhancing alpha- and beta-cell responsiveness to glucose. Two open-label, single-dose, randomized, crossover studies in healthy subjects (ages 18-45 years) inve...

journal_title：Journal of clinical pharmacology

authors： Sunkara G,Sabo R,Wang Y,He YL,Campestrini J,Rosenberg M,Howard D,Dole WP

更新日期：2007-09-01 00:00:00

abstract：:This report investigated safety and dosing recommendations of intravenous caspofungin in hepatic insufficiency. In the single-dose study, 8 patients each with mild and moderate hepatic insufficiency received 70 mg of caspofungin. In the multiple-dose study, 8 patients with mild hepatic insufficiency and 13 healthy mat...

journal_title：Journal of clinical pharmacology

authors： Mistry GC,Migoya E,Deutsch PJ,Winchell G,Hesney M,Li S,Bi S,Dilzer S,Lasseter KC,Stone JA

更新日期：2007-08-01 00:00:00

abstract：:Standard of care for ulcerative colitis involves long-term pharmacotherapy or colectomy. Approximately 20% to 30% of patients eventually require a colectomy because patients either do not respond or cannot tolerate the currently available pharmacotherapies. Advances in our knowledge of the pathophysiology of ulcerativ...

journal_title：Journal of clinical pharmacology

authors： Sands BE,Kaplan GG

更新日期：2007-08-01 00:00:00

abstract：:PRX-00023 is a novel, nonazapirone 5-HT1A agonist in clinical development for treatment of affective disorders. The objectives of the initial clinical phase I studies (a single ascending dose study and multiple dose-ascending and high-dose titration studies) were to measure the pharmacokinetics, pharmacodynamic (neuro...

journal_title：Journal of clinical pharmacology

authors： Iyer GR,Reinhard JF Jr,Oshana S,Kauffman M,Donahue S

更新日期：2007-07-01 00:00:00

abstract：:The approved antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate, were considered good candidates for a fixed-dose combination product that could be administered as a single pill once daily (qd), thereby simplifying existing treatment regimens and promoting patient adherence. As both drugs are extens...

journal_title：Journal of clinical pharmacology

authors： Blum MR,Chittick GE,Begley JA,Zong J

更新日期：2007-06-01 00:00:00

abstract：:This multicenter, open-label study evaluated the effects of multiple doses of peginterferon alfa-2b on the steadystate pharmacokinetics of methadone in 20 adults with hepatitis C virus infection who were enrolled in a methadone maintenance program. All subjects received peginterferon alfa-2b 1.5 mug/kg/wk for 4 weeks ...

journal_title：Journal of clinical pharmacology

authors： Gupta SK,Sellers E,Somoza E,Angles L,Kolz K,Cutler DL

更新日期：2007-05-01 00:00:00

abstract：:The objective of this study was to characterize the population pharmacokinetics of enfuvirtide in HIV-1-infected children and adolescents. HIV-infected patients received combination antiretroviral therapy, including enfuvirtide 2.0 mg/kg subcutaneously, twice daily. Serial and trough blood samples were collected up to...

journal_title：Journal of clinical pharmacology

authors： Zhang X,Lin T,Bertasso A,Evans C,Dorr A,Kolis SJ,Salgo M,Patel I,T20-310\/NV16056 Study Group.

更新日期：2007-04-01 00:00:00

abstract：:Golimumab is a fully human antitumor necrosis factor alpha (TNF-alpha) monoclonal antibody that is being developed for intravenous and subcutaneous administration. To assess the pharmacokinetics and safety of the intravenous formulation of golimumab, 36 adult subjects with rheumatoid arthritis were randomly assigned t...

journal_title：Journal of clinical pharmacology

authors： Zhou H,Jang H,Fleischmann RM,Bouman-Thio E,Xu Z,Marini JC,Pendley C,Jiao Q,Shankar G,Marciniak SJ,Cohen SB,Rahman MU,Baker D,Mascelli MA,Davis HM,Everitt DE

更新日期：2007-03-01 00:00:00

abstract：:The effect of pomegranate juice (PJ) or grapefruit juice (GFJ) on CYP3A activity was studied in vitro and in healthy human volunteers. In human liver microsomes, the mean 50% inhibitory concentrations (IC(50)) for PJ and GFJ versus CYP3A (triazolam alpha-hydroxylation) were 0.61% and 0.55%, (v/v) respectively, without...

journal_title：Journal of clinical pharmacology

authors： Farkas D,Oleson LE,Zhao Y,Harmatz JS,Zinny MA,Court MH,Greenblatt DJ

更新日期：2007-03-01 00:00:00

abstract：:Aliskiren is the first in a new class of orally active, direct renin inhibitors for the treatment of hypertension. This open-label, nonrandomized, single-center, parallel-group study compared the pharmacokinetics and safety of a single 300-mg oral dose of aliskiren in patients with mild, moderate, or severe hepatic im...

journal_title：Journal of clinical pharmacology

authors： Vaidyanathan S,Warren V,Yeh C,Bizot MN,Dieterich HA,Dole WP

更新日期：2007-02-01 00:00:00

abstract：:Recently, a new latanoprost ophthalmic solution containing cyclodextrins was developed. The purpose of the present work was to compare the stability, clinical efficacy, and adverse effect profile of this formulation with the innovator product. The innovator formulation was stable at 4 degrees C but exhibited degradati...

journal_title：Journal of clinical pharmacology

authors： Gonzalez JR,Baiza-Duran L,Quintana-Hau J,Tornero-Montaño R,Castaneda-Hernandez G,Ortiz M,Alarcon-Oceguera F,Beltran-Loustaunau M,Cortez-Gastelum M,Garcidueñas-Mejia J,Gomez-Bastar P,Jimenez-Roman J,Korder-Ortega V,Paczka-Zapata

更新日期：2007-01-01 00:00:00

abstract：:Bioavailability of pioglitazone and metformin, in 2 dose strengths, given either as a fixed-dose combination tablet or as coadministration of commercial tablets (coad), was studied in young healthy subjects in 2 separate studies. In study I (n = 63), single oral doses of 15-mg pioglitazone/500-mg metformin fixed-dose ...

journal_title：Journal of clinical pharmacology

authors： Karim A,Slater M,Bradford D,Schwartz L,Zhao Z,Cao C,Laurent A

更新日期：2007-01-01 00:00:00

abstract：:Grapefruit is rich in flavonoids, which have been demonstrated to have a preventive influence on many chronic diseases, such as cancer and cardiovascular disease. However, since the early 1990s, the potential health benefits of grapefruit have been overshadowed by the possible risk of interactions between drugs and gr...

journal_title：Journal of clinical pharmacology

authors： Mertens-Talcott SU,Zadezensky I,De Castro WV,Derendorf H,Butterweck V

更新日期：2006-12-01 00:00:00

abstract：:Inflammatory conditions, such as rheumatoid arthritis, reduce response to calcium channel and beta-adrenergic antagonists but not the angiotensin II type 1 receptor (AT(1)R) antagonist valsartan. Inflammation also reduces clearance of some drugs or active metabolite, thereby reducing response. Active (n = 14) and cont...

journal_title：Journal of clinical pharmacology

authors： Daneshtalab N,Lewanczuk RZ,Russell AS,Jamali F

更新日期：2006-11-01 00:00:00

abstract：:A double-blind, placebo-controlled, multiple oral dose escalation study was conducted to investigate the pharmacokinetics, safety, and tolerability of entecavir in healthy subjects. Eight subjects were assigned to each of the 3 dose panels (0.1 mg, 0.5 mg, and 1 mg or matched placebo once daily for 14 days). Blood and...

journal_title：Journal of clinical pharmacology

authors： Yan JH,Bifano M,Olsen S,Smith RA,Zhang D,Grasela DM,LaCreta F

更新日期：2006-11-01 00:00:00

abstract：:The population pharmacokinetics of desmopressin in children with nocturnal enuresis and in healthy adults were compared using a 1-compartment model with first-order absorption and first-order elimination. In addition, the model consisted of a number of transit compartments before absorption to describe a lag-time. The...

journal_title：Journal of clinical pharmacology

authors： Osterberg O,Savic RM,Karlsson MO,Simonsson US,Nørgaard JP,Walle JV,Agersø H

更新日期：2006-10-01 00:00:00

abstract：:The primary objective of this study was to identify intravenous regimens of tipifarnib that would mimic the systemic exposure obtained after the current twice-daily oral administration of tipifarnib. After determination of an intravenous dose that 6 subjects with advanced cancer could tolerate, another 26 subjects wer...

journal_title：Journal of clinical pharmacology

authors： Zhang S,Zannikos P,Awada A,Piccart-Gebhart M,Dirix LY,Fumoleau P,Verhaeghe T,Francois M,De Porre P

更新日期：2006-10-01 00:00:00

abstract：:Food and Drug Administration data show that most anti-depressant studies in youth do not show drug effect. The few positive studies used rigorous diagnostic screening procedures, suggesting major depressive disorder (MDD) may not be a persistent condition in a subgroup of youth. To investigate persistence of MDD, we s...

journal_title：Journal of clinical pharmacology

authors： Malone RP,Bennett DS,Delaney MA,Choudhury MS,Luebbert JF,Cater J

更新日期：2006-09-01 00:00:00

abstract：:To evaluate the effect of febuxostat on the pharmacokinetics of indomethacin and naproxen and vice versa, 2 multiple-dose, 3-period crossover studies were performed in healthy subjects. In study 1, subjects received febuxostat 80 mg once daily, indomethacin 50 mg twice daily, or both. In study 2, subjects received feb...

journal_title：Journal of clinical pharmacology

authors： Khosravan R,Wu JT,Joseph-Ridge N,Vernillet L

更新日期：2006-08-01 00:00:00

abstract：:The search for effective treatments of Alzheimer's disease (AD) is one of the major challenges facing modern medicine. Acetylcholinesterase (AChE) inhibitors (AChEIs) are effective for the treatment of mild to moderate AD, and memantine, an N-methyl-D-aspartate (NMDA) inhibitor, has been approved for moderate to sever...

journal_title：Journal of clinical pharmacology

authors： Geerts H,Grossberg GT

更新日期：2006-07-01 00:00:00

abstract：:This analysis was conducted to characterize the pharmacokinetics and pharmacodynamics of pegfilgrastim and to develop a pharmacokinetic-pharmacodynamic model to describe the granulopoietic effects of pegfilgrastim and the homeostatic regulation of pegfilgrastim clearance in healthy subjects. Pegfilgrastim serum concen...

journal_title：Journal of clinical pharmacology

authors： Roskos LK,Lum P,Lockbaum P,Schwab G,Yang BB

更新日期：2006-07-01 00:00:00

abstract：:Liraglutide is a once-daily glucagon-like peptide-1 analogue being developed for the treatment of type 2 diabetes. The aim of this study was to investigate the effect of age and gender on the pharmacokinetics of liraglutide. Eight male and 8 female subjects were recruited from an 18- to 45-year-old group and an over-6...

journal_title：Journal of clinical pharmacology

authors： Damholt B,Golor G,Wierich W,Pedersen P,Ekblom M,Zdravkovic M

更新日期：2006-06-01 00:00:00

abstract：:A drug-drug interaction study was conducted to determine whether ritonavir (200 mg; 4 doses over 2 days) alters the pharmacokinetic disposition of bupropion (75 mg; once) coadministered to 7 healthy volunteers in a placebo-controlled 2-way crossover study. Serum samples collected from 0 to 24 hours after bupropion adm...

journal_title：Journal of clinical pharmacology

authors： Hesse LM,Greenblatt DJ,von Moltke LL,Court MH

更新日期：2006-05-01 00:00:00

abstract：:The objective of this study was to measure the steady-state cerebrospinal fluid (CSF) concentration of LY450108 and LY451395 (positive modulators of AMPA receptors) in healthy subjects after the administration of 1 mg and 5 mg. Secondary objectives included the evaluation of safety, pharmacokinetics, and steady-state ...

journal_title：Journal of clinical pharmacology

authors： Jhee SS,Chappell AS,Zarotsky V,Moran SV,Rosenthal M,Kim E,Chalon S,Toublanc N,Brandt J,Coutant DE,Ereshefsky L

更新日期：2006-04-01 00:00:00

abstract：:The inhibitory effects of isoflavones (daidzein, genistein, and glycitein) on human cytochrome P450 (CYP) 2A6 activities were investigated. Daidzein, genistein, and glycitein uncompetitively inhibited nicotine C-oxidation catalyzed by recombinant CYP2A6 expressed in baculovirus-infected insect cells with Ki values of ...

journal_title：Journal of clinical pharmacology

authors： Nakajima M,Itoh M,Yamanaka H,Fukami T,Tokudome S,Yamamoto Y,Yamamoto H,Yokoi T

更新日期：2006-03-01 00:00:00

abstract：:In this investigation, the pharmacokinetic and pharmacodynamic properties were determined of multiple doses of sublingual tablets containing either buprenorphine alone or buprenorphine and naloxone. Subjects were experienced opiate users who received escalating doses (4-24 mg) of buprenorphine either alone or in combi...

journal_title：Journal of clinical pharmacology

authors： Ciraulo DA,Hitzemann RJ,Somoza E,Knapp CM,Rotrosen J,Sarid-Segal O,Ciraulo AM,Greenblatt DJ,Chiang CN

更新日期：2006-02-01 00:00:00

abstract：:The authors evaluated the effect of high-dose aspirin at a therapeutic dose, using chlorzoxazone as a probe for CYP2E1 enzyme activity. In a randomized, open-label, 2-way crossover study, 10 healthy men were treated 3 times daily for 6 days with 1 g aspirin or placebo. On day 7, 1 dose of 400 mg chlorzoxazone was admi...

journal_title：Journal of clinical pharmacology

authors： Park JY,Kim KA,Park PW,Ha JM

更新日期：2006-01-01 00:00:00