The Application of Physiologically Based Pharmacokinetic Modeling to Predict the Role of Drug Transporters: Scientific and Regulatory Perspectives.

abstract：:Amyotrophic lateral sclerosis (ALS) is a fatal disorder characterized by degeneration of the upper and lower motor neuron. Among the at least 25 known genes associated with familial (hereditary) and sporadic ALS, mutations in fused-in-sarcoma (FUS) and superoxide dismutase 1 (SOD1) have been extensively investigated i...

journal_title：Journal of clinical pharmacology

authors： Peikert K,Naumann M,Günther R,Wegner F,Hermann A

更新日期：2019-10-01 00:00:00

abstract：:The relationship between indenolol (an investigational agent) plasma levels and the drug's effect on blood pressure and heart rate was investigated after single and repeated once daily administration at two dosage levels (60 mg and 120 mg) in two different groups of patients with first or second stage hypertension, ac...

journal_title：Journal of clinical pharmacology

authors： Sega R,Mailland F,Colombo F,Groothold G,Pantarotto C,Guenzati G,Libretti A

更新日期：1985-07-01 00:00:00

abstract：:The effects of propafenone on the pharmacokinetics and pharmacodynamics of propranolol were evaluated in 12 healthy male subjects. Both propafenone and propranolol were each administered alone for one week followed by concomitant administration for an additional week. Blood samples, obtained at steady-state, were anal...

journal_title：Journal of clinical pharmacology

authors： Kowey PR,Kirsten EB,Fu CH,Mason WD

更新日期：1989-06-01 00:00:00

abstract：:The population pharmacokinetic (PK) profile of oral clonidine was characterized in newborns with neonatal abstinence syndrome, and significant covariates affecting its PK parameters were identified. Plasma clonidine concentration data were obtained from a clinical trial in which 36 newborns, aged 1 to 25 days (postnat...

journal_title：Journal of clinical pharmacology

authors： Xie HG,Cao YJ,Gauda EB,Agthe AG,Hendrix CW,Lee H

更新日期：2011-04-01 00:00:00

abstract：:Fosamprenavir (FPV) is the phosphate ester prodrug of the HIV-1 protease inhibitor amprenavir (APV). A pediatric population pharmacokinetic model for APV was developed and simulation was used to identify dosing regimens for pediatric patients receiving FPV in combination with ritonavir (RTV) which resulted in concentr...

journal_title：Journal of clinical pharmacology

authors： Barbour AM,Gibiansky L,Wire MB

更新日期：2014-02-01 00:00:00

abstract：:Guanfacine, an alpha 2 adrenoceptor agonist, was compared with prazosin hydrochloride for the treatment of patients with mild to moderate essential hypertension in an 8-week, double-blind, randomized, parallel evaluation to determine efficacy and safety. The study consisted of a 2-week screening/weaning period (phase ...

journal_title：Journal of clinical pharmacology

authors： Lewin A,Alderman MH,Mathur P

更新日期：1990-12-01 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：:The efficacy and safety of esmolol, a titratable intravenous beta-adrenergic blocking agent with a short elimination half-life (t 1/2 = 9.0 min) was evaluated in a multicenter open-label study for the treatment of supraventricular tachyarrhythmias (heart rate greater than 100 bpm). The study also investigated the feas...

journal_title：Journal of clinical pharmacology

authors： Das G,Tschida V,Gray R,Dhurandhar R,Lester R,McGrew F,Askenazi J,Kaplan K,Emanuele M,Turlapaty P

更新日期：1988-08-01 00:00:00

abstract：:The pharmacokinetics and pharmacodynamics of flunisolide were studied in healthy volunteers after inhalation. In the morning on the day the study began, volunteers inhaled 0.5 mg of flunisolide with and without oral administration of charcoal, or 1 mg, 2 mg, and 3 mg of flunisolide with concomitant administration of c...

journal_title：Journal of clinical pharmacology

authors： Möllmann H,Derendorf H,Barth J,Meibohm B,Wagner M,Krieg M,Weisser H,Knöller J,Möllmann A,Hochhaus G

更新日期：1997-10-01 00:00:00

abstract：:Guidelines have been developed by the Bureau of Drugs, FDA, for antinflammatory drug development. They address the problem of efficacy and safety testing but leave the definition of qualified investigators and appropriate subjects unstated. The natural history of rheumatoid arthritis, the most-studied chronic inflamma...

journal_title：Journal of clinical pharmacology

authors： Ehrlich GE

更新日期：1977-11-01 00:00:00

abstract：:Moricizine, a unique Class I antiarrhythmic agent, was orally administered with and without a meal to 24 healthy male subjects to determine the effect of food on moricizine absorption and bioavailability. Relative to the fasting state, a standardized breakfast delayed the time to peak plasma moricizine concentration (...

journal_title：Journal of clinical pharmacology

authors： Pieniaszek HJ Jr,Rakestraw DC,Schary WL,Williams RL

更新日期：1991-09-01 00:00:00

abstract：:The influence of the method of cimetidine administration on theophylline disposition was studied in nine healthy, cigarette smoking male volunteers. The treatment phases consisted of: A) theophylline alone, B) theophylline plus intermittent cimetidine therapy (300 mg IV every 6 hr), and C) theophylline in combination ...

journal_title：Journal of clinical pharmacology

authors： Gutfeld MB,Welage LS,Walawander CA,Wilton JH,Harrison NJ

更新日期：1989-07-01 00:00:00

abstract：:We administered 0.5-and 1.0-mg doses of bumetanide intravenously to eight normal subjects with and without pretreatment with probenecid. Probenecid did not effect either the cumulative response or the time course of response of bumetanide. These results are in contrast to results reported in dogs but consistent with s...

journal_title：Journal of clinical pharmacology

authors： Brater DC,Chennavasin P

更新日期：1981-07-01 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 human cytochrome P450 (CYP) isoforms mediating nortriptyline 10-hydroxylation have been identified using kinetic studies on heterologously expressed human CYPs and chemical inhibition studies on human liver microsomes. Nortriptyline was metabolized to E-10-hydroxynortriptyline by human lymphoblast-expressed CYPs 2...

journal_title：Journal of clinical pharmacology

authors： Venkatakrishnan K,von Moltke LL,Greenblatt DJ

更新日期：1999-06-01 00:00:00

abstract：:The objective of this study was to establish effects of liraglutide on the QTc interval. In this randomized, placebo-controlled, double-blind crossover study, 51 healthy participants were administered placebo, 0.6, 1.2, and 1.8 mg liraglutide once daily for 7 days each. Electrocardiograms were recorded periodically ov...

journal_title：Journal of clinical pharmacology

authors： Chatterjee DJ,Khutoryansky N,Zdravkovic M,Sprenger CR,Litwin JS

更新日期：2009-11-01 00:00:00

abstract：:The pharmacokinetics and pharmacodynamics of intravenous famotidine were evaluated in 10 infants ranging from 5 to 19 days of age who had a therapeutic indication for the prophylactic treatment of stress ulceration. After a 0.5-mg/kg infusion of famotidine, timed serum (n = 6), urine (24-hour collection), and repeated...

journal_title：Journal of clinical pharmacology

authors： James LP,Marotti T,Stowe CD,Farrar HC,Taylor BJ,Kearns GL

更新日期：1998-12-01 00:00:00

abstract：:The bioavailability and pharmacokinetics of dilevalol following oral and intravenous administration were investigated in 12 healthy male volunteers. Dilevalol HCl was administered as a 200-mg oral tablet and a 50-mg intravenous infusion using a randomized cross-over design. Blood and urine samples were collected over ...

journal_title：Journal of clinical pharmacology

authors： Kramer WG,Nagabhushan N,Affrime MB,Perentesis GP,Symchowicz S,Patrick JE

更新日期：1988-07-01 00:00:00

abstract：:Traditionally, Phase I tolerance trials have been done with normal volunteers to establish single- and multiple-dose tolerance. We feel that the justification for doing multiple-dose tolerance studies in normals is open to question and that, in fact, more pertinent data can be generated by using the appropriate patien...

journal_title：Journal of clinical pharmacology

authors： Weissman L

更新日期：1981-10-01 00:00:00

abstract：:A single evening dose of a clonidine-chlorthalidone combination (Combipres) was compared with the usual twice-daily schedule in 11 patients with essential hypertension. No significant difference was found between the blood pressures recorded on the two regimens or between morning and afternoon pressures on the once-da...

journal_title：Journal of clinical pharmacology

authors： Grossman SH,Gunnells JC

更新日期：1980-04-01 00:00:00

abstract：:The antihypertensive effect of enalaprilat (MK-422), an intravenous (IV), nonsulfhydryl converting-enzyme inhibitor, was evaluated in a double-blind study of 14 patients with mild to moderate hypertension. The seven patients in the treatment group initially received IV enalaprilat 1.25 mg q6h for 24 hours. Thereafter,...

journal_title：Journal of clinical pharmacology

authors： Evans RR,Henzler MA,Weber EM,DiPette DJ

更新日期：1987-05-01 00:00:00

abstract：:A pilot study of a small group of schizophrenic patients manifesting symptoms of a depressive nature was treated in a double-blind study in which viloxazine or a placebo was administered in combination with either chlorpromazine or haloperidol. There appeared to be no difference between the viloxazine-treated group an...

journal_title：Journal of clinical pharmacology

authors： Kurland AA,Nagaraju A

更新日期：1981-01-01 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：:Long-term prolactin excess is often accompanied by numerous metabolic complications. No previous study has compared the effect of statin therapy on circulating levels of cardiometabolic risk factors in patients with elevated and normal prolactin levels. The study population consisted of 3 age-, weight-, and lipid-matc...

journal_title：Journal of clinical pharmacology

authors： Krysiak R,Szkróbka W,Okopień B

更新日期：2019-01-01 00:00:00

abstract：:The in vitro plasma protein binding of warfarin was evaluated by ultrafiltration in plasma from seven normal subjects and seven patients with varying degrees of renal dysfunction. The unbound, or free, warfarin fraction was twice as high in the plasma samples withdrawn from patients with renal impairment than in the s...

journal_title：Journal of clinical pharmacology

authors： Bachmann K,Shapiro R,Mackiewicz J

更新日期：1976-10-01 00:00:00

abstract：:Lofexidine, an antihypertensive imidazoline derivative, was given to ten hypertensives on both a twice-daily and once-daily regimen, using routine blood pressure measurements and 24-hour Remler recording. Plasma renin activity and catecholamines were measured. After a dose titration with twice-daily doses, the total t...

journal_title：Journal of clinical pharmacology

authors： Garrett BN,Kaplan NM

更新日期：1981-04-01 00:00:00

abstract：:Data from 60 patients treated with amikacin were analyzed for factors associated with nephrotoxicity. In 42 of these patients, data were examined for factors associated with clinical outcome. Variables evaluated included patient weight, age, sex, serum creatinine level, creatinine clearance, duration of therapy, total...

journal_title：Journal of clinical pharmacology

authors： Williams PJ,Hull JH,Sarubbi FA,Rogers JF,Wargin WA

更新日期：1986-02-01 00:00:00

abstract：:The effect of rosuvastatin on the pharmacokinetics of digoxin was assessed in 18 healthy male volunteers in this double-blind, randomized, two-way crossover trial. Volunteers were dosed with rosuvastatin (40 mg once daily) or placebo to steady state before being given a single dose of digoxin 0.5 mg. Blood and urine s...

journal_title：Journal of clinical pharmacology

authors： Martin PD,Kemp J,Dane AL,Warwick MJ,Schneck DW

更新日期：2002-12-01 00:00:00

abstract：:The antipyretic activity of ibuprofen (Brufen) and paracetamol (Crocin) was compared in 22 children with pyrexia who received either ibuprofen or paracetamol in syrup form. Both axillary and rectal temperatures were recorded prior to drug administration and 1/2, 1, 2, 3, 4, 5, 6, 8, and 12 hours after dosing. Analysis...

journal_title：Journal of clinical pharmacology

authors： Sheth UK,Gupta K,Paul T,Pispati PK

更新日期：1980-11-01 00:00:00

abstract：:Adherence to microbicide gel use is critical to optimizing effectiveness in preventing human immunodeficiency virus transmission. The authors hypothesized that ester taggants added to vaginal gels would generate exhaled alcohol and ketone metabolites and provide a "breath test" for vaginal gel use. This 2-arm (vaginal...

journal_title：Journal of clinical pharmacology

authors： Morey TE,Wasdo S,Wishin J,Quinn B,van der Straten A,Booth M,Gonzalez D,Derendorf H,Melker RJ,Dennis DM

更新日期：2013-01-01 00:00:00