Abstract:
:This trial was conducted to evaluate the pharmacokinetics and safety of a sodium oxybate (gamma-hydroxybutyrate [GHB]) oral solution in narcoleptic patients after acute and chronic treatment. An open-label, two-period, two-treatment study design was used. Trial subjects included 13 patients with polysomnographically confirmed narcolepsy. The patients were administered a bedtime dose of 4.5 g of sodium oxybate while in a sleep research center. They were subsequently treated with sodium oxybate at the nightly dose of 4.5 g for 8 weeks. The patients then returned to the sleep center and were again treated with the 4.5-g sodium oxybate dose at bedtime. Blood samples (5 mL) were collected at 18 time points before and up to 7 hours after both the first dose of sodium oxybate and following 8 weeks of dosing. Plasma samples were analyzed for oxybate content by a validated liquid chromatography/tandem mass spectrometry (LC/MS/MS) method. Noncompartmental methods were applied in the determination of pharmacokinetic parameters from each patient's plasma oxybate concentration versus time curve. No serious adverse events were recorded, and all patients completed the study. Headache, enuresis, and leg cramps were reported as adverse experiences. With both acute and chronic dosing, sodium oxybate was rapidly absorbed and eliminated with an apparent half-life of about 40 minutes. The only changes observed in the kinetics of oxybate after 8 weeks of treatment were a 13% and 16% increase in peak concentration (C(max)) and systemic exposure (AUC), respectively. The pharmacokinetics of sodium oxybate in narcoleptic patients were not changed in any clinically significant manner when the drug was chronically administered. The drug was well tolerated.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Borgen LA,Okerholm RA,Lai A,Scharf MBdoi
10.1177/0091270003262795subject
Has Abstractpub_date
2004-03-01 00:00:00pages
253-7issue
3eissn
0091-2700issn
1552-4604pii
44/3/253journal_volume
44pub_type
临床试验,杂志文章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::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::This open-label study evaluated apixaban pharmacokinetics, pharmacodynamics, and safety in subjects with mild, moderate, or severe renal impairment and in healthy subjects following a single 10-mg oral dose. The primary analysis determined the relationship between apixaban AUC∞ and 24-hour creatinine clearance (CLcr )...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.633
更新日期:2016-05-01 00:00:00
abstract::Eleven subjects completed a clinical trial to determine the safety/tolerability of freeze-dried black raspberries (BRB) and to measure, in plasma and urine, specific anthocyanins-cyanidin-3-glucoside, cyanidin-3-sambubioside, cyanidin-3-rutinoside, and cyanidin-3-xylosylrutinoside, as well as ellagic acid. Subjects we...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1177/0091270005279636
更新日期:2005-10-01 00:00:00
abstract::A number of herbal preparations have been shown to interact with prescription medications secondary to modulation of cytochrome P450 (CYP) and/or P-glycoprotein (P-gp). The purpose of this study was to determine the influence of Panax ginseng on CYP3A and P-gp function using the probe substrates midazolam and fexofena...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1177/0091270011407194
更新日期:2012-06-01 00:00:00
abstract::This study was designed to investigate the multiple-dose pharmacokinetics, safety, and tolerability of the selective α4β2 nicotinic acetylcholine partial agonist, varenicline, in elderly (65-85 years old) nonsmokers. Fifty male and female subjects with normal renal function for their age were randomized to receive var...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1177/0091270010370461
更新日期:2011-04-01 00:00:00
abstract::Pain is a troublesome nonmotor symptom of Parkinson's disease (PD). This double-blind exploratory pilot study (NCT01744496) was the first to specifically investigate the effect of a dopamine agonist on PD-associated pain as primary outcome. Patients with advanced PD (ie, receiving levodopa) and at least moderate PD-as...
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.678
更新日期:2016-07-01 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
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1997.tb04299.x
更新日期:1997-12-01 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
pub_type: 临床试验,杂志文章
doi:10.1177/00912700122010933
更新日期:2001-09-01 00:00:00
abstract::Serial pharmacokinetic (PK) sampling in 1159 patients from TRITON-TIMI 38 was undertaken. A multilinear regression model was used to quantitatively predict prasugrel's active metabolite (Pras-AM) concentrations from its 2 downstream inactive metabolites. Population-based methods were then applied to Pras-AM concentrat...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/0091270009337942
更新日期:2009-08-01 00:00:00
abstract::Calcium-channel blockers have been shown to be both safe and effective for treatment of patients with systemic hypertension. These drugs reduce peripheral vascular resistance predominantly by the inhibition of transmembrane calcium ion fluxes in vascular smooth muscle, and by this mechanism can reduce elevated blood p...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1002/j.1552-4604.1993.tb05619.x
更新日期:1993-08-01 00:00:00
abstract::The objective of this study was to determine the absolute oral bioavailability and disposition of omapatrilat. This single-dose, randomized, crossover study of 20 mg intravenous and 50 mg oral [14C]omapatrilat was conducted in 12 healthy male subjects to determine the disposition and oral bioavailability of omapatrila...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/00912700122010726
更新日期:2001-08-01 00:00:00
abstract::Avibactam is a non-β-lactam β-lactamase inhibitor intended for use as a fixed-dose combination with ceftazidime for the treatment of certain serious Gram-negative infections. As avibactam is primarily excreted unchanged in the urine, renal impairment may affect its pharmacokinetics. This phase 1 study investigated the...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1002/jcph.793
更新日期:2017-02-01 00:00:00
abstract::The new antidepressant nomifensin (Hoechst 36984), a drug which showed less cardiotoxicity than tricyclics, was compared in a single-blind comparative trial with viloxazine. Forty elderly depressed patients were treated during four weeks. Nomifensin, N=21, 75 mg/day; viloxazine, N=19, 150 mg/day). Antidepressant effec...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1977.tb04589.x
更新日期:1977-01-01 00:00:00
abstract::Several approaches are available to estimate the glomerular filtration rate (GFR) from the sinistrin clearance. To compare such approaches, GFR was estimated in six healthy volunteers, both after a bolus injection and a bolus dose followed by a 6-hour infusion. A recently developed high-performance liquid chromatograp...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1997.tb04355.x
更新日期:1997-08-01 00:00:00
abstract::The type II histamine receptor antagonists, cimetidine and ranitidine, widely used in treatment of peptic ulcer disease have been reported to cause bradycardia. To evaluate the cardiovascular effects of H2 antagonists nineteen healthy volunteers were entered into a double-blind crossover comparison of cimetidine 300 m...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1989.tb03365.x
更新日期:1989-05-01 00:00:00
abstract::Nateglinide (Starlix, SDZ DJN 608 or A-4166), a new insulinotropic agent, is intended to be administered prior to a meal in order to improve early insulin release in non-insulin-dependent diabetes mellitus patients. The effects of a meal on the oral bioavailability and pharmacodynamic actions of nateglinide were inves...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/00912709922007606
更新日期:1999-02-01 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
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/j.1552-4604.1997.tb04273.x
更新日期:1997-10-01 00:00:00
abstract::Floctafenin (FFn), 2,3-dihydroxypropyl--N--(8--trifluoromethyl--4--quinolyl) anthranilate, a new nonnarcotic analgesic drug, was studied in man, mice, and the isolated perfused rat liver. In all species the drug is rapidly hydrolyzed to floctafenic acid (FFa). In seven volunteer subjects who each received a single ora...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1979.tb01613.x
更新日期:1979-01-01 00:00:00
abstract::Esmolol is an intravenous beta blocker with a short duration of action. The pharmacokinetics of esmolol and its acid metabolite, ASL-8123, were studied in nine patients who had stable, biopsy-proved Laennec's cirrhosis and in three normal volunteer controls. Kinetics were determined after a four-hour continuous infusi...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1987.tb05583.x
更新日期:1987-11-01 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::Although alcohol consumption is involved in most acts of violence, most people do not become violent when they drink. Individuals also respond differently to alcohol on laboratory measures of aggression. The objective of this study was to determine whether individual differences in the effects of alcohol on a laborato...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/0091270004270457
更新日期:2005-01-01 00:00:00
abstract::Weight loss has been associated with improvement in insulin sensitivity. It is consequently a cornerstone in the management of type 2 diabetes mellitus (T2DM). However, the strictly quantitative relationship between weight loss, insulin sensitivity, and clinically relevant glucose homeostasis biomarkers as well as cha...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1728
更新日期:2021-02-01 00:00:00
abstract::The alpha 1-adrenoceptor antagonists doxazosin and terazosin and the 5 alpha-reductase inhibitor finasteride are used in the treatment of benign prostatic hyperplasia. The aim of this study was to assess the potential pharmacokinetic interaction of doxazosin or terazosin when coadministered with finasteride. This was ...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1177/009127009803801113
更新日期:1998-11-01 00:00:00
abstract::Magnesium sulfate is the anticonvulsant of choice for eclampsia prophylaxis and treatment; however, the recommended dosing regimens are costly and cumbersome and can be administered only by skilled health professionals. The objectives of this study were to develop a robust exposure-response model for the relationship ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1448
更新日期:2019-11-01 00:00:00
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
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270010387792
更新日期:2011-12-01 00:00:00
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 so...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1998.tb04432.x
更新日期:1998-04-01 00:00:00
abstract::CBER's philosophy partners with the sponsor's philosophy in the development of electronic dossiers. Based on the experience gained from a number of dossiers, CBER has established a standard management paradigm and imaging platform by which the review of radiographs has been facilitated. ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/009127001773744297
更新日期:2001-07-01 00:00:00
abstract::The primary objective was to determine the pharmacokinetics of single oral and intravenous doses of pantoprazole in children 2 to 16 years of age. The secondary objective was to assess the safety and tolerability of these doses. Male and female hospitalized and nonhospitalized patients from ages 5 to 16 years received...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1177/0091270008321811
更新日期:2008-11-01 00:00:00
abstract::This study evaluated the effects of intravitreal injection of fasudil (IVF), a Rho-kinase inhibitor, in cases of recent-onset nonarteritic anterior ischemic optic neuropathy (NAION). In this interventional case series, 13 eyes of 13 patients diagnosed with NAION within 14 days of onset were included. The affected eyes...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.655
更新日期:2016-06-01 00:00:00