Abstract:
:This study was conducted to assess the effect of noninsulin-dependent diabetes mellitus (NIDDM) and gender on the pharmacokinetics of metformin and to investigate whether or not metformin exhibits dose-dependent pharmacokinetics. The pharmacodynamic effects (on plasma glucose and insulin) of metformin in patients with NIDDM and in healthy subjects also were assessed. Nine patients with NIDDM and 9 healthy subjects received 4 single-blind single-dose treatments of metformin HCL (850 mg, 1,700 mg, 2,550 mg, and placebo) and a multiple-dose treatment of 850 mg metformin HCL (3 times daily for 19 doses). After each single-dose treatment and the final dose of the multiple-dose phase, multiple plasma and urine samples were collected for 48 hours and assayed for metformin levels. Plasma samples were also assayed for glucose and insulin levels. There were no significant differences in metformin kinetics in patients with NIDDM compared with healthy subjects, in men compared with women, or during multiple-dose treatment versus single-dose treatment. Plasma concentrations of metformin increase less than proportionally to dose, most likely due to a decrease in percent absorbed. In patients with NIDDM, single doses of 1,700-mg or higher of metformin significantly decrease postprandial, but not preprandial, glucose concentrations and do not influence insulin concentrations. With multiple doses, both preprandial and postprandial glucose concentrations and preprandial insulin concentrations were significantly lower than with placebo. The effect of metformin on glucose level is correlated with the average fasting plasma glucose level without drug. In healthy subjects, single and multiple doses of metformin showed no effect on plasma glucose, but significantly attenuated the rise in immediate postprandial insulin levels.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Sambol NC,Chiang J,O'Conner M,Liu CY,Lin ET,Goodman AM,Benet LZ,Karam JHdoi
10.1177/009127009603601105subject
Has Abstractpub_date
1996-11-01 00:00:00pages
1012-21issue
11eissn
0091-2700issn
1552-4604journal_volume
36pub_type
临床试验,杂志文章,随机对照试验abstract::A selective thromboxane (TX) synthase inhibitor, CS-518, was orally administered to healthy male Japanese volunteers and the pharmacokinetic and pharmacodynamic properties were investigated. The time profile of drug concentrations in plasma was determined, and the effects of the drug on platelet aggregation in plasma ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1994.tb03964.x
更新日期:1994-01-01 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::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
pub_type: 杂志文章
doi:10.1177/0091270005284192
更新日期:2006-02-01 00:00:00
abstract::The relative analgesic potency of oral and intramuscular oxymorphone was evaluated in a double-blind crossover comparison of graded single doses in patients with chronic pain due to cancer. When both duration and intensity of analgesia are considered (total effect), oral oxymorphone was 1/6 as potent as the intramuscu...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1177/009127007701700402
更新日期:1977-04-01 00:00:00
abstract::Tafenoquine is being developed for relapse prevention in Plasmodium vivax malaria. This Phase I, single-blind, randomized, placebo- and active-controlled parallel group study investigated whether tafenoquine at supratherapeutic and therapeutic concentrations prolonged cardiac repolarization in healthy volunteers. Subj...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1002/jcph.302
更新日期:2014-09-01 00:00:00
abstract::In ten patients (age: 47-59 yr) with moderately severe essential hypertension, the humoral and hemodynamic effects of a 4-day therapy with 2 x 75 micrograms clonidine, 2 x 20 mg nifedipine (slow-release), and their combination were investigated and compared with baseline values. The following measurements were observe...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1991.tb03736.x
更新日期:1991-06-01 00:00:00
abstract::As part of a clinical trial investigating the level of nicotine replacement with different doses of transdermal therapy for smoking cessation, urine excretion rates of nicotine and cotinine were measured in 70 subjects while they were actively smoking (baseline) and for 6 consecutive inpatient days while they were rec...
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.1552-4604.1998.tb05788.x
更新日期:1998-06-01 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::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
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1177/0091270007299760
更新日期:2007-05-01 00:00:00
abstract::Quinapril, a nonsulfhydryl ACE inhibitor, was evaluated in ten New York Heart Association (NYHA) functional class (FC) II-III CHF patients to determine its effects on regional blood flow [effective renal plasma flow (ERPF), renal blood flow (RBF), renal vascular resistance (RVR), hepatic blood flow (HBF), hepatic vasc...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1992.tb03791.x
更新日期:1992-01-01 00:00:00
abstract::Enalapril maleate (MK-421) is a new non-sulfhydryl-containing converting-enzyme inhibitor that has been shown to be effective and well tolerated in patients with essential hypertension. Data on its effectiveness and safety in patients with renovascular hypertension are limited and have involved predominantly short-ter...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/009127008702700105
更新日期:1987-01-01 00:00:00
abstract::Repaglinide is a novel insulin secretagogue developed in response to the need for a fast-acting, oral prandial glucose regulator for the treatment of type 2 (non-insulin-dependent) diabetes mellitus. Repaglinide is metabolized mainly in the liver; its pharmacokinetics may therefore be altered by hepatic dysfunction. T...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1177/00912700022008793
更新日期:2000-02-01 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
pub_type: 杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract::The objective of this study is to identify gender-related differences in the types of symptoms and drugs reported to cause an adverse drug reaction. Patient data from the Sunnybrook Health Science Centre ADR Clinic for the period from April 1986 to May 1996 were reviewed. Of the 2,367 patients assessed, 74.1% were fem...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/009127009803801103
更新日期:1998-11-01 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
pub_type: 杂志文章
doi:10.1177/0091270007300953
更新日期:2007-07-01 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
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1177/0091270006299089
更新日期:2007-04-01 00:00:00
abstract::Eight healthy men received 100 mg oral doses of etretinate separated by two-week washout periods in an open, randomized, crossover study. Etretinate was administered during a complete fast, with a standard high fat breakfast, a standard high carbohydrate breakfast, and 16 ounces of whole milk. Plasma samples were obta...
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.1552-4604.1985.tb02881.x
更新日期:1985-11-01 00:00:00
abstract::It is well known that the CYP2C19 genetic polymorphism influences the pharmacokinetics and pharmacodynamics of proton pump inhibitors (PPIs), but no report has addressed the effects on ilaprazole, a newly developed PPI. To investigate the effects of the CYP2C19 genetic polymorphism on the disposition and pharmacodynam...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/0091270011408611
更新日期:2012-07-01 00:00:00
abstract:BACKGROUND:L-threo-3,4-dihydroxyphenylserine (L-DOPS), a norepinephrine (NE) prodrug, is investigational for orthostatic hypotension, which occurs commonly in Parkinson's disease. Adjunctive anti-parkinsonian drugs might interact with L-DOPS. We tested whether L-aromatic amino-acid decarboxylase inhibition by carbidopa...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270010363476
更新日期:2011-01-01 00:00:00
abstract::The effects of long-term triple drug therapy on renal function in patients with moderate to severe essential hypertension have not been evaluated systematically. We prospectively studied fifteen male patients with moderate to severe essential hypertension receiving triple drug therapy (metolazone, atenolol or betaxolo...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1989.tb03423.x
更新日期:1989-09-01 00:00:00
abstract::GS-9667, a new selective, partial agonist of the A(1) adenosine receptor (AR), may represent an effective therapy for Type 2 diabetes (T2DM) and dyslipidemia via lowering of free fatty acids (FFA). The objectives of the studies were to evaluate the effects of single and multiple doses of GS-9667 on plasma FFA concentr...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.9
更新日期:2013-04-01 00:00:00
abstract::The present study was carried out to clarify the effects of an antianxiety drug and of personality characteristics on a psychomotor performance test. Forty-eight healthy women college students were chosen from 64 volunteers as having either high or low levels of trait anxiety, neuroticism, or extroversion. Subjects wi...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1978.tb02432.x
更新日期:1978-02-01 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
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/j.1552-4604.1998.tb04377.x
更新日期:1998-01-01 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
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/j.1552-4604.1988.tb05751.x
更新日期:1988-05-01 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
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270006293304
更新日期:2006-11-01 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::Microdialysis is a technique that allows the measurement of free antibiotic concentrations in different tissues, which are responsible for the antibacterial activity at the infection site. In an open, randomized, 2-way crossover study in healthy volunteers, the muscle penetration of orally administered cefpodoxime (40...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/0091270004273679
更新日期:2005-05-01 00:00:00
abstract::Anemia is a well-known RBV-related event in HCV therapy which is exacerbated by the addition of telaprevir and boceprevir. This retrospective study evaluated and compared ribavirin exposure and parameters able to influence hemoglobin decrease in a large population of patients treated with dual or triple therapy. Patie...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.454
更新日期:2015-05-01 00:00:00
abstract::The effect of bilastine on cardiac repolarization was studied in 30 healthy participants during a multiple-dose, triple-dummy, crossover, thorough QT study that included 5 arms: placebo, active control (400 mg moxifloxacin), bilastine at therapeutic and supratherapeutic doses (20 mg and 100 mg once daily, respectively...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/0091270011407191
更新日期:2012-06-01 00:00:00
abstract::The interactive effects of the coadministration of steady-state cimetidine and single-dose pentopril, an angiotensin converting enzyme inhibitor, on the pharmacokinetic disposition of each other were studied in humans. Cimetidine reduced the clearance of pentopril by 11 to 14%. This reduction in clearance was shown to...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1988.tb03136.x
更新日期:1988-03-01 00:00:00