Abstract:
:The enhanced nonenzymatic isomerization of pravastatin to SQ 31,906, a relatively inactive metabolite, has been demonstrated to occur on exposure to gastric acidity in humans. However, the effect of gastric metabolism on the pharmacodynamics of pravastatin has not been studied. In addition, it was hypothesized that some individuals may be more extensive gastric metabolizers than others. Sixteen men received 4 weeks of oral therapy with pravastatin 10 mg after a 6-week drug washout diet run-in period. Pharmacokinetic and pharmacodynamic parameters were determined after 8 hours of serum sampling on the final day of therapy. Patients with a metabolic ratio for area under the concentration-time curve (AUC0-8 of pravastatin/AUC0-8 of SQ 31,906) of less than 1.6 had a significantly lower reduction in total and low-density lipoprotein (LDL) cholesterol compared with those with a ratio > 1.6. An enteric formulation of pravastatin should increase the bioavailability of pravastatin and enhanced lipid-lowering efficacy.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Ito MKdoi
10.1002/j.1552-4604.1998.tb04432.xsubject
Has Abstractpub_date
1998-04-01 00:00:00pages
331-6issue
4eissn
0091-2700issn
1552-4604journal_volume
38pub_type
临床试验,杂志文章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
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270011434157
更新日期:2013-01-01 00:00:00
abstract::The absolute bioavailability of oral melatonin tablets was studied in 12 normal healthy volunteers. Subjects were administered, in a randomized crossover fashion, melatonin 2 mg intravenously and 2 and 4 mg orally. Blood was sampled over approximately eight (estimated) half-lives. Both the 2 and the 4 mg oral dosages ...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/00912700022009422
更新日期:2000-07-01 00:00:00
abstract::Although people living with human immunodeficiency virus and other comorbidities are expected to experience more grievous consequences with corona virus disease 2019 (COVID-19), recent cohort studies did not indicate this. Antiretrovirals (ARVs) might have a prophylactic role in these patients. The purpose of this stu...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1788
更新日期:2020-11-20 00:00:00
abstract::With increasing interest in enrolling adolescent patients in adult trials, a question often arises: when can pediatric patients use adult dosages? For currently approved therapeutic monoclonal antibodies (mAbs) with equivalent adult and pediatric indications, body weight thresholds for pediatric patients to receive ad...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1434
更新日期:2019-10-01 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
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270009339189
更新日期:2009-11-01 00:00:00
abstract::Nineteenth century ophthalmology, characterized by significant gains in diagnostic techniques, provided the basis for great advancements in treatment during the 20th century. Drug therapy at the turn of the century was empiric, palliative, and often toxic. The development of ocular pharmacology during the 20th century...
journal_title:Journal of clinical pharmacology
pub_type: 历史文章,杂志文章
doi:10.1177/00912700022009710
更新日期:2000-09-01 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
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1989.tb03373.x
更新日期:1989-06-01 00:00:00
abstract::This multicenter, randomized, open-label, parallel-group, phase-1 study assessed the pharmacokinetics (PK), safety, and tolerability of the investigational intramuscular paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia or schizoaffective disorder. A total of 328 patients (men or women, ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1002/jcph.597
更新日期:2016-03-01 00:00:00
abstract::The safety, antiretroviral activity, and pharmacokinetic profile of nelfinavir, a potent and specific inhibitor of human immunodeficiency virus (HIV) protease, were assessed in a small open-label phase I/II dose-ranging study in protease inhibitor-naive HIV-positive men. A total of 22 patients with baseline plasma HIV...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1998.tb04814.x
更新日期:1998-08-01 00:00:00
abstract::The effect of food on the pharmacokinetics of 15 mg oxybutynin XL was evaluated in a single-dose, randomized, crossover, open-label study in healthy volunteers. A validated, stereospecific, high-performance liquid chromatography assay was used to simultaneously determine the plasma concentrations of R- and S-oxybutyni...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/00912700122010014
更新日期:2001-02-01 00:00:00
abstract::This report briefly discusses some aspects of autonomic cardiovascular dysfunction as related to changes in orthostatic function in patients, bed rest subjects, and astronauts. This relationship is described in normal individuals to provide the basis for discussion of parameters that may be altered in patients, bed re...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1002/j.1552-4604.1993.tb01944.x
更新日期:1993-11-01 00:00:00
abstract::As the United States seeks a greater presence in space, physiologic changes associated with space flight become of greater concern. Exposure to a weightless environment has been shown to have numerous effects on body composition and organ function. Alterations include decreases in muscle and liver mass, changes in bon...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1002/j.1552-4604.1994.tb02023.x
更新日期:1994-06-01 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
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270007300951
更新日期:2007-06-01 00:00:00
abstract::We compared the pharmacokinetic (PK) exposure parameters of efavirenz (EFV) and its major inactive metabolite, 8-hydroxy-efavirenz (8-OH-EFV), in an open-label, single-sequence, and parallel design of HIV-infected and tuberculosis (TB)-HIV-coinfected Ethiopian patients in the HIV-TB Pharmagene study with 20 and 33 pat...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1002/jcph.756
更新日期:2016-12-01 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
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1177/0091270006292626
更新日期:2007-01-01 00:00:00
abstract::Varenicline is a novel selective α4β2 nicotinic acetylcholine partial agonist developed for smoking cessation. Single- and multiple dose studies were conducted to investigate pharmacokinetics, safety, and tolerability of varenicline in healthy male Japanese smokers. The single-dose study was conducted as a double-blin...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270010372388
更新日期:2011-04-01 00:00:00
abstract::Although physiologic modeling has not gained the widespread acceptance that was originally projected, it may serve as the basis for future PK/PD modeling approaches. In addition, with more effort applied to developing in vitro and animal-to-human predictions, physiologic modeling may assume a higher position in the ph...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1002/j.1552-4604.1988.tb03199.x
更新日期:1988-08-01 00:00:00
abstract::A decrease in dietary protein intake lowers the clearance of a number of substances excreted principally by the kidney including uric acid and oxypurinol, the major metabolite of allopurinol. We studied the kinetics of uric acid and oxypurinol in seven healthy volunteers on a normal protein diet (2600 calories; 100 g ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1989.tb03239.x
更新日期:1989-01-01 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
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1981.tb01772.x
更新日期:1981-07-01 00:00:00
abstract::Four protease inhibitor antiviral agents (ritonavir, indinavir, nelfinavir, saquinavir) were evaluated as in vitro inhibitors of the activity of six human cytochromes using an in vitro model based on human liver microsomes. Ritonavir was a highly potent inhibitor of P450-3A activity (triazolam hydroxylation), having i...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1998.tb04398.x
更新日期:1998-02-01 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
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270011408728
更新日期:2012-07-01 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
pub_type: 临床试验,杂志文章
doi:10.1177/0091270002251004
更新日期:2003-03-01 00:00:00
abstract::Cyclophosphamide-based regimens are front-line treatment for numerous pediatric malignancies; however, current dosing methods result in considerable interpatient variability in tumor response and toxicity. In this pediatric population, the authors' objectives were (1) to quantify and explain the pharmacokinetic variab...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1177/0091270008325928
更新日期:2009-01-01 00:00:00
abstract::Limited data characterize pharmacokinetic interactions between cephalexin and ranitidine, and no data exist for an interaction with proton pump inhibitors. The purpose of this study was to investigate the effects of ranitidine or omeprazole administration on the pharmacokinetics and pharmacodynamics of cephalexin. A r...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/0091270004269558
更新日期:2004-12-01 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
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270007309706
更新日期:2008-01-01 00:00:00
abstract::Approximately equianalgesic oral doses of codeine, an oxycodone compound resembling Percodan, and pentazocine were compared for adverse effects in a double-blind, randomized study of four doses of each drug given over two days to 247 postsurgical patients with pain. Placebo and parenteral morphine were also treated as...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/j.1552-4604.1981.tb01724.x
更新日期:1981-01-01 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
pub_type: 杂志文章
doi:10.1177/0091270010396373
更新日期:2012-03-01 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
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1987.tb03041.x
更新日期:1987-05-01 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
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1981.tb05697.x
更新日期:1981-04-01 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
pub_type: 临床试验,杂志文章
doi:10.1177/009127002762491307
更新日期:2002-11-01 00:00:00