"Cocktail" approaches and strategies in drug development: valuable tool or flawed science?

abstract：:Aprepitant or its prodrug fosaprepitant, in combination with a corticosteroid and a 5-HT(3) receptor antagonist, are used to prevent chemotherapy-induced nausea and vomiting. This study evaluated the effect of fosaprepitant 150 mg on CYP3A4 metabolism. Fosaprepitant 150 mg has been submitted to regulatory agencies for...

journal_title：Journal of clinical pharmacology

authors： Marbury TC,Ngo PL,Shadle CR,Jin B,Panebianco D,Caro L,Valentine J,Murphy G

更新日期：2011-12-01 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 bioequivalence study of two oral formulations of 300 mg ranitidine was carried out in 16 healthy volunteers (8 men and 8 women), and the pharmacokinetics in both sexes were compared. There was bioequivalence of both formulations. The terminal half-life of ranitidine was 7% shorter and the oral apparent clearance 10....

journal_title：Journal of clinical pharmacology

authors： Abad-Santos F,Carcas AJ,Guerra P,Govantes C,Montuenga C,Gómez E,Fernández A,Frias J

更新日期：1996-08-01 00:00:00

abstract：:The efficacy of a eutectic mixture of local anesthetics (EMLA) in alleviating the pain associated with subcutaneous needle insertion for infusion of the iron-chelating agent, deferoxamine, was examined in 12 patients with homozygous beta-thalassemia. As reported by the patient using a 100-mm visual analogue scale, the...

journal_title：Journal of clinical pharmacology

authors： Berkovitch M,Davis S,Matsui D,Donsky J,Koren G,Olivieri NF

更新日期：1995-03-01 00:00:00

abstract：:Axitinib is a potent and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, approved for second-line therapy for advanced renal cell carcinoma (RCC). Axitinib population pharmacokinetic and pharmacokinetic/pharmacodynamic relationships were evaluated. Using nonlinear mixed effects modelin...

journal_title：Journal of clinical pharmacology

authors： Rini BI,Garrett M,Poland B,Dutcher JP,Rixe O,Wilding G,Stadler WM,Pithavala YK,Kim S,Tarazi J,Motzer RJ

更新日期：2013-05-01 00:00:00

abstract：:Sixteen essential hypertensive patients were entered into a protocol assessing the effect of Spirapril, an angiotensin-converting enzyme (ACE) inhibitor, on blood pressure, the renin-aldosterone system, and renal function. Specifically monitored before, during 6 weeks, and 6 months of Spirapril therapy were plasma ren...

journal_title：Journal of clinical pharmacology

authors： Reams GP,Lau A,Knaus V,Bauer JH

更新日期：1993-04-01 00:00:00

abstract：:Nine patients with resistant hypertension received captopril for 12 months. Five received captopril alone, four required additional therapy. In the former, mean blood pressure fell from 109 +/- 4.2 mm Hg to 84 +/- 7.5 mm Hg (P less than 0.025) after seven days. A rise to 101 +/- 19 mm Hg was noted at six and 12 months...

journal_title：Journal of clinical pharmacology

authors： Sullivan JM,Taylor JC,Patrick DR,Johnson JG,Ratts TE,Muirhead EE

更新日期：1982-10-01 00:00:00

abstract：:Droxicam is a nonsteroidal anti-inflammatory drug that is a pro-drug of piroxicam. The influence of concomitant administration of antacid or ranitidine on droxicam pharmacokinetics has been investigated. On three separate phases, 15 healthy volunteers received a single oral 20-mg dose of droxicam either alone, with an...

journal_title：Journal of clinical pharmacology

authors： Bartlett A,Costa A,Martínez L,Roser R,Sagarra R,Sánchez J

更新日期：1992-12-01 00:00:00

abstract：:The pharmacokinetics, safety, and preliminary efficacy of FTY720, a novel immunomodulator, were examined in de novo renal transplant patients. Both noncompartmental and population methods were used to estimate pharmacokinetic estimates in the patients. The steady-state plasma concentrations of FTY720 increased in acco...

journal_title：Journal of clinical pharmacology

authors： Skerjanec A,Tedesco H,Neumayer HH,Cole E,Budde K,Hsu CH,Schmouder R

更新日期：2005-11-01 00:00:00

abstract：:We show that for drugs metabolized by one enzyme the slope of a plot of serum concentration (C) versus 1/clearance (CL) is linear with a value of 1/Vmax in the presence of substrate saturation and may be linear (rarely) or curved (usually) with a slope always greater than 1/Vmax in the presence of substrate saturation...

journal_title：Journal of clinical pharmacology

authors： Browne TR,Szabo GK,Walsh CT,Schumacher GE,Evans JE,Evans BA

更新日期：1990-07-01 00:00:00

abstract：:Twenty healthy volunteers (age ranging from 19 to 72) were studied for their aldosterone response to oral administration of 10 mg cisapride, a serotonin-4 receptor agonist. The participants were studied after minimum of 4-hour ambulation (high basal renin) and a repeated test after overnight bed rest (low basal renin)...

journal_title：Journal of clinical pharmacology

authors： Huang YY,Hsu BR,Tsai JS

更新日期：1997-12-01 00:00:00

abstract：:The pharmacokinetic profile of solifenacin succinate (YM905; Vesicare), a new once-daily bladder-selective muscarinic receptor antagonist, was examined in 2 controlled trials of healthy young men. A single-dose study evaluated 5-, 10-, 20-, 40-, 60-, 80-, and 100-mg doses. A multidose study evaluated 5-, 10-, 20-, and...

journal_title：Journal of clinical pharmacology

authors： Smulders RA,Krauwinkel WJ,Swart PJ,Huang M

更新日期：2004-09-01 00:00:00

abstract：:An open-label, randomized, crossover study was performed in healthy male volunteers to evaluate the potential pharmacokinetic and pharmacodynamic interactions and tolerability of single oral doses of modafinil (200 mg) and dextroamphetamine (10 mg). Blood samples were collected for determination of plasma levels of mo...

journal_title：Journal of clinical pharmacology

authors： Wong YN,Wang L,Hartman L,Simcoe D,Chen Y,Laughton W,Eldon R,Markland C,Grebow P

更新日期：1998-10-01 00:00:00

abstract：:A vast and continuously growing amount of material on drugs exists in the literature to read and evaluate. Frequently, the papers and their recommendations are conflicting and contradictory. Readers are faced with the dilemma of deciding what to believe. The need for evidence-based medicine as a foundation for optimal...

journal_title：Journal of clinical pharmacology

authors： Spector R,Vesell ES

更新日期：2002-09-01 00:00:00

abstract：:The purpose of this analysis was to develop a population pharmacokinetic model for CS-917, an oral hypoglycemic prodrug, and its 3 metabolites. The population pharmacokinetic model was used to predict exposure of the active moiety R-125338 and thus to identify potential CS-917 dosage reduction criteria. The dataset in...

journal_title：Journal of clinical pharmacology

authors： Kastrissios H,Walker JR,Carrothers TJ,Kshirsagar S,Khariton T,Habtemariam B,Mager DE,Rohatagi S

更新日期：2012-03-01 00:00:00

abstract：:A novel, nonscrotal, transdermal delivery system for testosterone therapy has been marketed for treatment of hypogonadal men. The usual dose of this system is two 2.5 mg/day systems applied daily. A new system has been developed that administers a dose of 5 mg/day using a single patch rather than two patches. A random...

journal_title：Journal of clinical pharmacology

authors： Wilson DE,Meikle AW,Boike SC,Fairless AJ,Etheredge RC,Jorkasky DK

更新日期：1998-01-01 00:00:00

abstract：:CS-0777 is a selective sphingosine 1-phosphate receptor-1 (S1P(1)) modulator under development for treatment of autoimmune conditions. A randomized, double-blind, placebo-controlled study was conducted to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of CS-0777 in escalat...

journal_title：Journal of clinical pharmacology

authors： Moberly JB,Rohatagi S,Zahir H,Hsu C,Noveck RJ,Truitt KE

更新日期：2012-07-01 00:00:00

abstract：:To study the pharmacokinetics and pharmacodynamics of two intravenous nizatidine dosing regimens, serial plasma concentrations and continuous intragastric pH were monitored simultaneously in 10 subjects with a documented history of duodenal or gastric ulcers. A 24-hour gastric pH profile was characterized for a 300 mg...

journal_title：Journal of clinical pharmacology

authors： Danziger L,Furmaga KM,Rodvold KA,Bombeck CT,Fischer JH

更新日期：1989-10-01 00:00:00

abstract：:The role of dopaminergic receptors on renal function has been extensively studied. Recently dopaminergic receptor has been classified in two subtypes D1 and D2, which seem to have different modulatory function. However, the role of dopaminergic receptors on cardiovascular function and more specifically the potential r...

journal_title：Journal of clinical pharmacology

authors： Luchsinger A,Velasco M,Urbina A,Morillo J,Romero E,Alvarez R,Pieretti OH

更新日期：1992-01-01 00:00:00

abstract：:This study assessed the efficacy and safety of ketoprofen patch compared with placebo in patients who had rheumatoid arthritis and persistent wrist pain. Patients (N = 676)who had achieved systemic disease control with a disease-modifying antirheumatic drug and/or systemic corticosteroid, but still had persistent wris...

journal_title：Journal of clinical pharmacology

authors： Kawai S,Uchida E,Kondo M,Ohno S,Obata J,Nawata Y,Sugimoto K,Oribe M,Nagaya I

更新日期：2010-10-01 00:00:00

abstract：:Pharmacokinetic studies of i.v. and oral racemic verapamil and 14C-erythromycin breath tests (ERBT) were performed in 84 healthy men (n = 42) and women (n = 42). Verapamil was measured by HPLC, concentration versus time data were analyzed by noncompartmental models, protein binding was measured by equilibrium dialysis...

journal_title：Journal of clinical pharmacology

authors： Krecic-Shepard ME,Barnas CR,Slimko J,Jones MP,Schwartz JB

更新日期：2000-03-01 00:00:00

abstract：:The disposition of nalmefene, an opioid antagonist intended for the reversal of opioid-induced respiratory depression, and its primary metabolite nalmefene glucuronide, were characterized in adult volunteers with normal renal function and in patients with end-stage renal disease (ESRD). The effect of hemodialysis on t...

journal_title：Journal of clinical pharmacology

authors： Matzke GR,Frye RF,Alexander AC,Reynolds R,Dixon R,Johnston J,Rault RM

更新日期：1996-02-01 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：:Argatroban, a direct thrombin inhibitor, is metabolized in vitro by CYP3A4/5 and therefore may be susceptible to clinically relevant CYP3A drug interactions. The effect of erythromycin, a potent CYP3A4/5 inhibitor, on the pharmacokinetics and pharmacodynamics of argatroban was evaluated in 14 healthy male volunteers i...

journal_title：Journal of clinical pharmacology

authors： Tran JQ,Di Cicco RA,Sheth SB,Tucci M,Peng L,Jorkasky DK,Hursting MJ,Benincosa LJ

更新日期：1999-05-01 00:00:00

abstract：:Intravenous administration of acetaminophen is an alternative to the oral and rectal routes, which may be contraindicated in particular clinical settings. This randomized, placebo-controlled study of intravenous acetaminophen (Ofirmev, Mallinckrodt Pharmaceuticals, Bedminster, New Jersey) in neonate and infant patient...

journal_title：Journal of clinical pharmacology

authors： Hammer GB,Maxwell LG,Taicher BM,Visoiu M,Cooper DS,Szmuk P,Pheng LH,Gosselin NH,Lu J,Devarakonda K

更新日期：2020-01-01 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：:The effects of graded doses of anisotropine methylbromide on nocturanl gastric secretion were investigated in a double-blind crossover study in man. Single doses considerably higher than those usually employed for daytime use in adjunctive therapy of peptic ulcer disease significantly reduced acid secretion without si...

journal_title：Journal of clinical pharmacology

authors： Freston JW,Forbes JA

更新日期：1977-01-01 00:00:00

abstract：:A pediatric population pharmacokinetic model including covariate effects was developed using data from 2 clinical trials in pediatric patients with epilepsy (SP0847 and SP1047). Lacosamide plasma concentration-time data (n = 402) were available from 79 children with body weights ranging from 6 to 76 kg, and a balanced...

journal_title：Journal of clinical pharmacology

authors： Winkler J,Schoemaker R,Stockis A

更新日期：2019-04-01 00:00:00

abstract：:Renal electrolyte excretion patterns were determined in nonedematous healthy volunteers following bumetanide and furosemide in two separate clinical studies. In study 1, intravenous bumetanide was administered to 24 subjects at four dose levels. In study 2, bumetanide (1 or 2 mg) or furosemide (40 or 80 mg) was admini...

journal_title：Journal of clinical pharmacology

authors： Hutcheon DE,Vincent ME,Sandhu RS

更新日期：1981-11-01 00:00:00

abstract：:The incidence of migraine is higher among women than men and peaks during the reproductive years, when contraceptive medication use is common. Atogepant, a potent, selective antagonist of the calcitonin gene-related peptide receptor-in development for migraine prevention-is thus likely to be used by women taking oral ...

journal_title：Journal of clinical pharmacology

authors： Ankrom W,Xu J,Vallee MH,Dockendorf MF,Armas D,Boinpally R,Min KC

更新日期：2020-09-01 00:00:00