Abstract:
:To investigate the impact of cytochrome P450 (CYP) genetic polymorphisms CYP2B6, CYP2C19, and CYP3A5 on mRNA expression, cyclophosphamide/4-hydroxycyclophosphamide pharmacokinetics, and treatment outcomes of the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in Chinese patients with non-Hodgkin's lymphoma, 567 cases were investigated. Plasma concentrations of cyclophosphamide/4-hydroxycyclophosphamide were determined using liquid chromatography-tandem mass spectrometry and pharmacokinetic parameters calculated. The frequencies of CYP2B6*1/*29 and CYP2B6*1/*30 were 18 (3.2%) and 30 (5.3%), respectively. Liver samples with CYP2B6*29/*30, CYP2C19*2, CYP2B6*6, or CYP3A5*3 had significantly lower target mRNA expression. Samples with CYP2B6*6 and/or CYP2C19*2 had lower exposure to 4-hydroxycyclophosphamide, whereas those with CYP2B6*1G/*1H had higher exposure. Multivariate model showed that samples with CYP2C19*2 or CYP2B6 785A>raG had worse treatment response than samples with CYP3A5*3. CYP2C19*2, CYP2B6*6, CYP2B6*29, and CYP2B6*30 were protective factors for toxicity in the multivariate model. The best model for gene-gene interactions for treatment response contained CYP2C19*2, CYP2B6 785A>G, and CYP3A5*3 (cross-validation consistency [CVC], 8/10; P = .0035). The best prediction model for grade 2-4 toxicities had CYP2C19*2, CYP2B6 785A>G, and 516 G>T (CVC, 10/10; P < .0001). In previous reports, we were the first to report that the frequency of copy-number variations in CYP2B6 is higher among Chinese than among other ethnic populations. Genetic variations in CYP2B6, CYP2C19, and CYP3A5 dramatically affected the mRNA expression of proteins, the pharmacokinetics of 4-hydroxycyclophosphamide, and the R-CHOP treatment response in Chinese subjects. Patients carrying CYP3A5*3 were more likely to have a better treatment response, whereas patients with CYP2C19*2 or CYP2B6 516G>T, or CYP2B6 785A>G had higher tolerance to treatment.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Shu W,Chen L,Hu X,Zhang M,Chen W,Ma L,Liu X,Huang J,Pang T,Li J,Zhang Ydoi
10.1002/jcph.878subject
Has Abstractpub_date
2017-07-01 00:00:00pages
886-898issue
7eissn
0091-2700issn
1552-4604journal_volume
57pub_type
杂志文章abstract::Oral contraceptives (OCs) are the most widely used form of birth control among women of childbearing potential. Knowledge of potential drug-drug interactions (DDIs) with OCs becomes imperative to provide information on the medication to women of childbearing potential and enable their inclusion in clinical trials, esp...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1765
更新日期:2020-12-01 00:00:00
abstract::Twenty young (45 years or younger) and 20 older (55 years or older) adult patients with mild hypertension were enrolled in this study to compare the hemodynamic effects of labetalol versus placebo in two age groups. Ten patients in each group were randomly assigned to receive either a single oral dose of labetalol (20...
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.tb03153.x
更新日期:1988-04-01 00:00:00
abstract::The intravenous infusion of cetiedil to a group of ten male volunteers elicited atropine-like side effects on salivation, bronchomotor tone and visual accommodation. With repeated infusions of cetiedil, the incidence as well as the duration of the side effects were reduced significantly, indicating the development of ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1982.tb02668.x
更新日期:1982-05-01 00:00:00
abstract::Grapefruit is rich in flavonoids, which have been demonstrated to have a preventive influence on many chronic diseases, such as cancer and cardiovascular disease. However, since the early 1990s, the potential health benefits of grapefruit have been overshadowed by the possible risk of interactions between drugs and gr...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1177/0091270006294277
更新日期:2006-12-01 00:00:00
abstract::The aim of this study was to determine the relationship, precision, and bias of a propofol target-controlled infusion (TCI) system during prolonged infusion in neurosurgical patients. We retrospectively included patients undergoing general anesthesia for elective neurosurgical removal of brain tumors and postoperative...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1060
更新日期:2018-05-01 00:00:00
abstract::This study evaluated the pharmacodynamics and pharmacokinetics of once-daily dosing of warfarin at steady state when taken concomitantly with once-daily doses of duloxetine. Healthy subjects with a stable international normalized ratio (INR) of 1.5 to 2.0 on an individualized fixed dose of warfarin (2-9 mg) in period ...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/0091270009344335
更新日期:2009-12-01 00:00:00
abstract::The pharmacokinetics of a meloxicam suspension were studied in 18 children with juvenile rheumatoid arthritis. Children received a single 0.25-mg/kg dose up to a maximum of 15 mg. Pharmacokinetic parameters after the first dose were calculated by noncompartmental methods. Geometric mean (percent coefficient of variati...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1177/0091270004267589
更新日期:2004-08-01 00:00:00
abstract::A single-center, double-blind, placebo-controlled, randomized study was conducted to determine the pharmacokinetics, safety, and tolerability of single, rising intramuscular (i.m.) doses and the single maximum tolerated dose of parecoxib sodium, a prodrug of the novel COX-2 selective anti-inflammatory analgesic drug v...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/00912700122012607
更新日期:2001-10-01 00:00:00
abstract::Data from 58 premarketing studies of the nonsteroidal antiinflammatory drug flurbiprofen were pooled for analyses of adverse drug reactions (ADRs). These studies included 5602 patients treated with flurbiprofen (N = 4123), aspirin (N = 1033), or placebo (N = 446) for varying durations. Diagnoses included rheumatoid ar...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1990.tb03604.x
更新日期:1990-04-01 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::Ciramadol, a new analgesic with mixed narcotic agonist-antagonist actions, was compared with codeine and placebo in a double-blind study in 343 patients with postoperative pain. The patients received a single oral dose of either 30 or 60 mg of ciramadol, 60 mg of codeine, or placebo. As indicated by three efficacy mea...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1985.tb02882.x
更新日期:1985-11-01 00:00:00
abstract::ABT-335 is the choline salt of fenofibric acid under clinical development as a combination therapy with rosuvastatin for the management of dyslipidemia. ABT-335 and rosuvastatin have different mechanisms of actions and exert complementary pharmacodynamic effects on lipids. The current study assessed the pharmacokineti...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270008325671
更新日期:2009-01-01 00:00:00
abstract::Caffeine has been used frequently in the treatment and prevention of apnea of prematurity. The metabolism of caffeine depends on the activities of the hepatic enzymes that vary from one infant to another. The objective of this study was to determine the influence of postnatal age (PNA), birth weight (BW), study weight...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/00912700122010500
更新日期:2001-06-01 00:00:00
abstract::The benzothiadiazide diuretics are known to cause magnesium and potassium wasting and retention of calcium and uric acid. The effect of magnesium replacement on diuretic-induced changes in sodium, potassium, calcium, and magnesium balance, weight, and blood pressure was studied in 12 normal subjects and 13 hypertensiv...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1978.tb01582.x
更新日期:1978-11-01 00:00:00
abstract::Evolocumab binds PCSK9, increasing low-density lipoprotein cholesterol (LDL-C) receptors and lowering LDL-C. Target-mediated evolocumab elimination is attributable to PCSK9 binding. As circulating PCSK9 and LDL-C levels are primarily regulated by the liver, we compared evolocumab pharmacokinetics, pharmacodynamics, an...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.832
更新日期:2017-04-01 00:00:00
abstract::The objective of this study was to establish effects of inhaled loxapine on the QTc interval in this randomized, placebo-controlled, double-blind crossover study. Forty-eight healthy volunteers received a single inhaled placebo or 10 mg loxapine. Plasma concentrations of loxapine increased with a median Tmax of 1 minu...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1002/jcph.257
更新日期:2014-06-01 00:00:00
abstract::The pharmacokinetics, pharmacodynamics, and safety of fosinopril sodium (SQ 28,555), a new orally active angiotensin-converting enzyme (ACE) inhibitor, was evaluated in 73 healthy men in two separate studies. In study I, doses ranging from 10 to 640 mg were administered once daily for 3 days to seven groups of five su...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1991.tb01887.x
更新日期:1991-01-01 00:00:00
abstract::To investigate whether methyldopa alters digoxin disposition, eight healthy subjects received methyldopa titrated to 250 mg t.i.d. or placebo in a double-blind, cross-over manner for 16 consecutive days, with 0.25 mg intravenous digoxin coadministered on day 5 and 0.25 mg oral digoxin on days 9 to 16. Digoxin concentr...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1984.tb02791.x
更新日期:1984-08-01 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::Of 17,068 hospitalized medical patients monitored in a drug surveillance program, 616 (3.6 per cent) received pentazocine hydrochloride orally and 816 (4.8 per cent) received pentazocine lactate parenterally during one or more admissions. Unsatisfactory analgesic efficacy as judged by each patient's physician was near...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1975.tb02357.x
更新日期:1975-02-01 00:00:00
abstract::A double-blind, crossover study was carried out to compare the antihypertensive efficacy of the long-acting ACE inhibitor trandolapril 1 mg administered once daily and 0.5 mg twice daily in 31 patients with mild to moderate essential hypertension. After randomization, patients entered a single-blind placebo period of ...
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.1552-4604.1993.tb01959.x
更新日期:1993-09-01 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
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1985.tb02851.x
更新日期:1985-07-01 00:00:00
abstract::The pharmacokinetics of isoproterenol (ISO) in infants and children have never been reported. The authors studied ISO pharmacokinetics in two disparate groups of pediatric intensive care unit patients: postoperative cardiac patients (POC, n = 10), and reactive airway disease patients (RAD, n = 9). In all, 44 blood sam...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1993.tb03899.x
更新日期:1993-01-01 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
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/0091270006289848
更新日期:2006-08-01 00:00:00
abstract::The pharmacokinetic actions, bioequivalence, and cardiovascular effects of two verapamil products were studied in a randomized, double-blind, crossover study in eight elderly hypertensive patients (median age, 69.5 years; range, 60-79 years) given brand-name or generic immediate-release verapamil in 120-mg twice-daily...
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.tb04331.x
更新日期:1997-06-01 00:00:00
abstract::Type 2 diabetes has now reached epidemic proportions across the world and is the cause of substantial morbidity and mortality. Patients with diabetes suffer from their mircovascular complications of retinopathy (blindness), nephropathy (renal failure, dialysis), and neuropathy (neropathic pain, trophic ulcers). Howeve...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1177/0091270004263045
更新日期:2004-04-01 00:00:00
abstract::Calcium channel blocker therapy has proved protective in certain models of ischemic-induced acute renal failure. This effect may be related to the prevention of calcium influx into injured cells or by the vasodilatory effects of verapamil that may result in an improvement in renal blood flow. In the current study, the...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1987.tb03076.x
更新日期:1987-08-01 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::The Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), the German drug regulation authority, issued guidelines for determining whether bioavailability/bioequivalence studies are required for certain drugs. This decision tree is based on pharmacodynamic, pharmacokinetic, and physicochemical criteria. Details ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1998.tb04385.x
更新日期:1998-10-01 00:00:00
abstract::These studies were conducted to evaluate the pharmacokinetics of several retinoids after meal consumption or vitamin A supplementation to establish a reference for future assessment of teratogenic risks of retinoid therapeutic agents. In the first study, 36 healthy young female volunteers consumed single meals contain...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1996.tb04253.x
更新日期:1996-09-01 00:00:00