Dose selection for the investigational anticancer agent alisertib (MLN8237): Pharmacokinetics, pharmacodynamics, and exposure-safety relationships.

abstract：:Migraine is a common and debilitating disorder of uncertain pathogenesis. Recent research into the pathophysiology of migraine and serotonin receptors has revolutionized the approach to pharmacotherapy. New medications, such as sumatriptan, and new dosage forms of older medications, including dihydroergotamine, NSAIDs...

journal_title：Journal of clinical pharmacology

authors： Solomon GD

更新日期：1993-03-01 00:00:00

abstract：:Nifedipine kinetics have not been described in clinically relevant detail because of difficulties in formulating a stable preparation for intravenous use and lack of a specific and sensitive assay for plasma nifedipine. We recently developed a gas-chromatographic method and determined conditions in which nifedipine co...

journal_title：Journal of clinical pharmacology

authors： Foster TS,Hamann SR,Richards VR,Bryant PJ,Graves DA,McAllister RG

更新日期：1983-04-01 00:00:00

abstract：:Pharmacokinetics (PK) of doripenem was determined during high volume hemodiafiltration (HVHDF) in patients with septic shock. A single 500 mg dose of doripenem was administered as a 1 hour infusion during HVHDF to 9 patients. Arterial blood samples were collected before and at 30 or 60 minute intervals over 8 hours (1...

journal_title：Journal of clinical pharmacology

authors： Tamme K,Oselin K,Kipper K,Low K,Standing JF,Metsvaht T,Karjagin J,Herodes K,Kern H,Starkopf J

更新日期：2015-04-01 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：:Sixteen healthy male volunteers received a single oral dose of 25 mg doxylamine succinate. Doxylamine concentrations in plasma were measured by a newly developed gas chromatographic methodology, utilizing direct alkaline extraction into hexane:isoamyl alcohol followed by concentration and autoinjection. Doxylamine kin...

journal_title：Journal of clinical pharmacology

authors： Friedman H,Greenblatt DJ

更新日期：1985-09-01 00:00:00

abstract：:The extension of the previously developed integrated models for glucose and insulin (IGI) to include the oral glucose tolerance test (OGTT) in healthy volunteers could be valuable to better understand the differences between healthy individuals and those with type 2 diabetes mellitus (T2DM). Data from an OGTT in 23 he...

journal_title：Journal of clinical pharmacology

authors： Silber HE,Frey N,Karlsson MO

更新日期：2010-03-01 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：:Interactions between tolvaptan and digoxin were determined in an open-label, sequential study where 14 healthy subjects received tolvaptan 60 mg once daily (QD) on days 1 and 12 to 16 and digoxin 0.25 mg QD on days 5 to 16. Mean maximal concentrations (C(max)) and area under the curve during the dosing interval (AUC(τ...

journal_title：Journal of clinical pharmacology

authors： Shoaf SE,Ohzone Y,Ninomiya S,Furukawa M,Bricmont P,Kashiyama E,Mallikaarjun S

更新日期：2011-05-01 00:00:00

abstract：:Assessment of drug-induced venodilation by the dorsal hand vein compliance method requires stable constriction of the vein. This study was designed to investigate intra- and intersubject reproducibility of the venous preconstriction technique in response to phenylephrine and prostaglandin F2 alpha and to determine the...

journal_title：Journal of clinical pharmacology

authors： Schindler C,Grossmann M,Dobrev D,Francke K,Ravens U,Kirch W

更新日期：2003-03-01 00:00:00

abstract：:The pharmacokinetics of codeine, codeine glucuronide, morphine, and morphine glucuronide were assessed after single- (60 mg) and multiple-dose (60 mg every six hours for nine doses) oral administration of codeine sulfate to six normal volunteers. Multiple blood and urine samples were collected after administration of ...

journal_title：Journal of clinical pharmacology

authors： Guay DR,Awni WM,Halstenson CE,Findlay JW,Opsahl JA,Abraham PA,Jones EC,Matzke GR

更新日期：1987-12-01 00:00:00

abstract：:HMR1031 is a potent and specific antagonist of the integrin VLA-4 (alpha4beta1) binding to vascular cell adhesion molecule-1 (VCAM-1) and fibronectin. HMR1031 is an inhaled drug being developed for the treatment of asthma using an Ultrahaler dry-powder inhalation device. A pharmacoscintigraphic study of HMR1031 sugges...

journal_title：Journal of clinical pharmacology

authors： Shah B,Jensen BK,Zhang J,Hunt T,Rohatagi S

更新日期：2003-12-01 00:00:00

abstract：:Pentoxifylline, a nonselective phosphodiesterase inhibitor, has immunomodulatory activity in vitro and in vivo and potentiates the suppressive effects of glucocorticoids and cyclosporine on lymphocyte proliferation in vitro. Since phosphodiesterase isotypes 3 and 4 predominate in lymphocytes, the authors measured the ...

journal_title：Journal of clinical pharmacology

authors： Briggs WA,Wu Q,Orgul O,Choi M,Scheel PJ Jr,Burdick J

更新日期：1999-08-01 00:00:00

abstract：:Effective antiretroviral (ARV)-based HIV prevention strategies require optimizing drug exposure in mucosal tissues; yet factors influencing mucosal tissue disposition remain unknown. We hypothesized drug transporter expression in vaginal, cervical, and colorectal tissues is a contributing factor and selected 3 efflux ...

journal_title：Journal of clinical pharmacology

authors： Nicol MR,Fedoriw Y,Mathews M,Prince HM,Patterson KB,Geller E,Mollan K,Mathews S,Kroetz DL,Kashuba AD

更新日期：2014-05-01 00:00:00

abstract：:The possible effect of oral flecainide acetate on steady-state digoxin levels was assessed in 15 healthy men. Each volunteer received digoxin 0.25 mg daily (8 AM) for 22 consecutive days and flecainide 200 mg bid (8 AM and 8 PM) on days 11 through 15. Plasma digoxin and flecainide levels were measured by radioimmunoas...

journal_title：Journal of clinical pharmacology

authors： Weeks CE,Conard GJ,Kvam DC,Fox JM,Chang SF,Paone RP,Lewis GP

更新日期：1986-01-01 00:00:00

abstract：:A single-dose, randomized, double-blind study of parallel design was conducted to determine the analgesic efficacy and safety of ketorolac tromethamine in patients who experience moderate or severe pain after the surgical removal of three or more third molars, one of which was a bony-impacted mandibular molar. Meperid...

journal_title：Journal of clinical pharmacology

authors： Fricke JR Jr,Angelocci D,Fox K,McHugh D,Bynum L,Yee JP

更新日期：1992-04-01 00:00:00

abstract：:The pharmacokinetics of butorphanol nasal spray, with and without the coadministration of metoclopramide, were studied in 24 healthy women. In this crossover study all volunteers received 3 treatments: a single, 1-mg dose of butorphanol nasal spray, a single, 10-mg oral dose of metoclopramide, and a combination of a s...

journal_title：Journal of clinical pharmacology

authors： Vachharajani NN,Shyu WC,Barbhaiya RH

更新日期：1997-10-01 00:00:00

abstract：:Unresolved issues of ethical, methodological, and legal concerns in the use of normal healthy volunteers persist. Financial incentives in their recruitment offer a unique ethical dilemma because of questions surrounding payment. A review of literature was conducted to obtain research systematically examining volunteer...

journal_title：Journal of clinical pharmacology

authors： Tishler CL,Bartholomae S

更新日期：2002-04-01 00:00:00

abstract：:Patients with heart failure (HF) are at increased risk for drug-induced torsades de pointes (TdP) due to unknown mechanisms. Our objective was to determine if sensitivity to drug-induced QT interval lengthening is enhanced in patients with HF. In this multicenter, prospective study, 15 patients with atrial fibrillatio...

journal_title：Journal of clinical pharmacology

authors： Tisdale JE,Overholser BR,Wroblewski HA,Sowinski KM,Amankwa K,Borzak S,Kingery JR,Coram R,Zipes DP,Flockhart DA,Kovacs RJ

更新日期：2012-09-01 00:00:00

abstract：:Antibody-drug conjugates (ADCs) represent an innovative therapeutic approach that provides novel treatment options and hope for patients with cancer. By coupling monoclonal antibodies (mAbs) to cytotoxic small-molecule payloads with a plasma-stable linker, ADCs offer the potential for increased drug specificity and fe...

journal_title：Journal of clinical pharmacology

authors： Vezina HE,Cotreau M,Han TH,Gupta M

更新日期：2017-10-01 00:00:00

abstract：:Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3-by-1 design). These studies are challenging and expensive to conduct, ty...

journal_title：Journal of clinical pharmacology

authors： Zeng Y,Singh S,Wang K,Ahrens RC

更新日期：2018-04-01 00:00:00

abstract：:Effective and practical preventive procedures for postflight orthostatic intolerance are highly desirable. The current practice of attempts to expand plasma volume by ingestion of salt and fluids before reentry has proven benefits. This study evaluated alternative options using fludrocortisone (F) to expand plasma vol...

journal_title：Journal of clinical pharmacology

authors： Vernikos J,Dallman MF,Van Loon G,Keil LC

更新日期：1991-10-01 00:00:00

abstract：:In many industrialized nations, the elderly comprise the fastest growing subpopulation and constitute an increasing proportion of the total population compared to other age groups. The elderly use a disproportionately larger amount of health care resources since they experience a higher incidence of disease-related mo...

journal_title：Journal of clinical pharmacology

authors： Schmucker DL,Vesell ES

更新日期：1999-11-01 00:00:00

abstract：:To test the effects of fluvastatin on low-density lipoprotein (LDL) receptor activity in patients with heterozygous familial hypercholesterolemia, the authors measured LDL receptor activity in stimulated T-lymphocytes prepared from 34 patients before and after treatment with 40 mg fluvastatin daily for 12 weeks. Maxim...

journal_title：Journal of clinical pharmacology

authors： Raungaard B,Brorholt-Petersen JU,Jensen HK,Faergeman O

更新日期：2000-04-01 00:00:00

abstract：:The purpose of this study was to characterize the effect of potent CYP2D6 inhibition byparoxetine on atomoxetine disposition in extensive metabolizers. This was a single-blind, two-period, sequential studyin 22 healthy individuals. In period 1, 20 mg atomoxetine bid was administered to steady state. In period 2, 20 mg...

journal_title：Journal of clinical pharmacology

authors： Belle DJ,Ernest CS,Sauer JM,Smith BP,Thomasson HR,Witcher JW

更新日期：2002-11-01 00:00:00

abstract：:The effect of 6% hydroxyethyl starch (hetastarch) and 5% human serum albumin (albumin) infusion on coagulation in 12 patients with septic shock was evaluated. Patients were randomly assigned to receive either albumin (N = 6) or hetastarch (N = 6) infusion over a 24-hour study interval. The prothrombin time (PT), parti...

journal_title：Journal of clinical pharmacology

authors： Falk JL,Rackow EC,Astiz ME,Weil MH

更新日期：1988-05-01 00:00:00

abstract：:Compared with aminoglycosides, chloramphenicol, sulfonamides, tetracyclines, and even penicillins, the cephalosporins represent a remarkably safe class of antibiotics. Among the cephalosporins, the extended spectrum, third generation agents developed generally produce few side effects and appear to be less allergenic ...

journal_title：Journal of clinical pharmacology

authors： Neu HC

更新日期：1990-05-01 00:00:00

abstract：:Cyclosporin G (CSG) has produced less nephrotoxicity than cyclosporin A (CSA) at equivalent doses in animal models. Conflicting results have been reported concerning differences in the pharmacokinetics of CSA and CSG in preclinical studies, and no data exist regarding the effect of steady-state oral administration of ...

journal_title：Journal of clinical pharmacology

authors： Gruber SA,Gallichio M,Rosano TG,Kaplan SS,Hughes SE,Urbauer DL,Singh TP,Lempert N,Conti DJ,Stein DS,Drusano G

更新日期：1997-07-01 00:00:00

abstract：:The aim of the study was to investigate the pharmacokinetics and removal of midazolam and unconjugated and glucuronidated 1-hydroxy-midazolam in 4 intensive care patients on continuous venovenous hemodialysis. Plasma midazolam and its metabolites were assessed by HPLC from blood samples collected during continuous inf...

journal_title：Journal of clinical pharmacology

authors： Bolon M,Bastien O,Flamens C,Paulus S,Boulieu R

更新日期：2001-09-01 00:00:00

abstract：:Everolimus is an immunosuppressant intended for use with cyclosporine in acute-rejection prophylaxis following organ transplantation. The possibility of a drug interaction of cyclosporine on everolimus was assessed. In this randomized, two-period, crossover study, 24 healthy subjects received a single oral dose of 2 m...

journal_title：Journal of clinical pharmacology

authors： Kovarik JM,Kalbag J,Figueiredo J,Rouilly M,Frazier OL,Rordorf C

更新日期：2002-01-01 00:00:00

abstract：:The safety and pharmacokinetics of single and multiple administrations of cefpirome (HR810), a new cephalosporin antibiotic agent with a broad antibacterial spectrum, were studied in healthy male volunteers. The single administration protocols included a 3-minute intravenous injection of 0.5 g or 1 g, and a 1-hour int...

journal_title：Journal of clinical pharmacology

authors： Nakayama I,Akieda Y,Yamaji E,Nitta Y,Ohishi M,Katagiri K,Imamura N,Takase K

更新日期：1992-03-01 00:00:00