The importance of both CYP2C19 and CYP2B6 germline variations in cyclophosphamide pharmacokinetics and clinical outcomes.

Abstract:

:Cyclophosphamide is an alkylating agent used in the treatment of solid and haematological malignancies and as an immunosuppressive agent. As a prodrug, it is dependent on bioactivation to the active phosphoramide mustard metabolite to elicit its therapeutic effect. This focused review will highlight the evidence for the role of germline pharmacogenetic variation in both plasma pharmacokinetics and clinical outcomes. There is a substantial indication from 13 pharmacokinetic and 17 therapeutic outcome studies, in contexts as diverse as haematological malignancy, breast cancer, systemic lupus erythematosus and myeloablation, that pharmacogenetic variation in both CYP2C19 and CYP2B6 influence the bioactivation of cyclophosphamide. An additional role for pharmacogenetic variation in ALDH1A1 has also been reported. Future studies should comprehensively assess these 3 pharmacogenes and undertake appropriate statistical analysis of gene-gene interactions to confirm these findings and may allow personalised treatment regimens.

journal_name

Br J Clin Pharmacol

authors

Helsby NA,Yong M,van Kan M,de Zoysa JR,Burns KE

doi

10.1111/bcp.14031

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

1925-1934

issue

9

eissn

0306-5251

issn

1365-2125

journal_volume

85

pub_type

杂志文章,评审
  • Excretion of doxepin and N-desmethyldoxepin in human milk.

    abstract::Doxepin and N-desmethyldoxepin concentrations in plasma and breast milk from a lactating mother and in plasma from her infant were measured during an 8 week period using high performance liquid chromatography. Plasma concentrations ranged from 35-68 microgram l-1 for doxepin and 65-131 microgram l-1 for N-desmethyldox...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1985.tb05106.x

    authors: Kemp J,Ilett KF,Booth J,Hackett LP

    更新日期:1985-11-01 00:00:00

  • Flavonoids inhibit the platelet TxA(2) signalling pathway and antagonize TxA(2) receptors (TP) in platelets and smooth muscle cells.

    abstract:AIMS:Flavonoids may affect platelet function by several mechanisms, including antagonism of TxA(2) receptors (TP). These TP are present in many tissues and modulate different signalling cascades. We explored whether flavonoids affect platelet TP signalling, and if they bind to TP expressed in other cell types. METHODS...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.2007.02881.x

    authors: Guerrero JA,Navarro-Nuñez L,Lozano ML,Martínez C,Vicente V,Gibbins JM,Rivera J

    更新日期:2007-08-01 00:00:00

  • Anti-hypertensive dose-response effects of nicardipine in stable essential hypertension.

    abstract::The dose-response effects of oral nicardipine on the systemic blood pressure were examined in 54 patients with uncomplicated essential hypertension (DBP greater than or equal to 100 mm Hg). The study was designed in four sequential stages. A 2 week single-blind placebo run-in period was followed by dose titration with...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1111/j.1365-2125.1985.tb05156.x

    authors: Taylor SH,Frais MA,Lee P,Verma SP,Jackson N,Silke B

    更新日期:1985-01-01 00:00:00

  • The pharmacokinetics of endralazine in essential hypertensives and in normotensive subjects.

    abstract::The direct-acting vasodilator, endralazine, in combination with a beta-adrenoceptor blocker significantly reduced the blood pressures of normotensive volunteers and of patients with essential hypertension. The mean terminal elimination half-life for endralazine of 136 min in hypertensive patients did not differ signif...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1983.tb02139.x

    authors: Meredith PA,Elliott HL,McSharry DR,Kelman AW,Reid JL

    更新日期:1983-07-01 00:00:00

  • Short-term sucralfate administration alters potassium diclofenac absorption in healthy male volunteers.

    abstract:AIMS:Since patients who regularly take NSAIDS may use sucralfate because of its cytoprotective properties, we examined the influence of this compound on the pharmacokinetics of diclofenac. METHODS:Potassium diclofenac (105 mg) was administered orally to eighteen healthy male volunteers with or without a 5-day pre-trea...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1111/j.1365-2125.1997.tb00040.x

    authors: Pedrazzoli Júnior J,Pierossi Mde A,Muscará MN,Dias HB,da Silva CM,Mendes FD,de Nucci G

    更新日期:1997-01-01 00:00:00

  • A mechanism-based binding model for the population pharmacokinetics and pharmacodynamics of omalizumab.

    abstract:AIM:Omalizumab, a humanized IgG monoclonal antibody that binds to human immunoglobulin E (IgE), interrupts the allergic cascade in asthmatic patients. The aim was to compare simultaneously drug exposure and IgE biomarker responses in Japanese and White patient populations. METHODS:An instantaneous equilibrium drug-lig...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,多中心研究

    doi:10.1111/j.1365-2125.2006.02803.x

    authors: Hayashi N,Tsukamoto Y,Sallas WM,Lowe PJ

    更新日期:2007-05-01 00:00:00

  • Comparison of gentamicin dose estimates derived from manual calculations, the Australian 'Therapeutic Guidelines: Antibiotic' nomogram and the SeBA-GEN and DoseCalc software programs.

    abstract:AIM:To compare gentamicin dose estimates from four predictive methods. METHODS:A retrospective study was conducted, comprising patients at Fremantle Hospital who received gentamicin therapy and had at least one gentamicin serum concentration reported. A manual calculation method, the Australian 'Therapeutic Guidelines...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.2004.02201.x

    authors: Mohan M,Batty KT,Cooper JA,Wojnar-Horton RE,Ilett KF

    更新日期:2004-11-01 00:00:00

  • Lisinopril and nifedipine: no acute interaction in normotensives.

    abstract::1. A double-blind, four period crossover study was undertaken to test for an interaction between single oral doses of nifedipine retard (20 mg) and lisinopril (20 mg) in normal subjects. 2. Side effects with both drugs were mild and the incidence was additive. 3. Blood pressure (BP) was lowered by nifedipine for 4 h, ...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1111/j.1365-2125.1988.tb03308.x

    authors: Lees KR,Reid JL

    更新日期:1988-03-01 00:00:00

  • Potentially inappropriate medications in geriatric outpatients with polypharmacy: application of six sets of published explicit criteria.

    abstract:AIM:Our aim was to compare the practicability of six different potentially inappropriate medication (PIM) criteria in geriatric outpatients with polypharmacy. METHODS:We analysed baseline data from the Medication Safety Review Clinic in Taiwanese Elders (MSRC-Taiwan) study. The prevalence and correlates of PIMs were d...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.2011.04010.x

    authors: Chang CB,Chen JH,Wen CJ,Kuo HK,Lu IS,Chiu LS,Wu SC,Chan DC

    更新日期:2011-09-01 00:00:00

  • Central nervous system toxicity of mefenamic acid overdose compared with other NSAIDs: an analysis of cases reported to the United Kingdom National Poisons Information Service.

    abstract:AIMS:Case reports and small case series suggest increased central nervous system (CNS) toxicity, especially convulsions, after overdose of mefenamic acid, compared with other nonsteroidal anti-inflammatory drugs (NSAIDs), although comparative epidemiological studies have not been conducted. The current study compared r...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/bcp.13169

    authors: Kamour A,Crichton S,Cooper G,Lupton DJ,Eddleston M,Vale JA,Thompson JP,Thomas SH

    更新日期:2017-04-01 00:00:00

  • The rates of common adverse events reported during treatment with proton pump inhibitors used in general practice in England: cohort studies.

    abstract:AIMS:To estimate the rates of common adverse events in patients treated with the proton pump inhibitors omeprazole, lansoprazole and pantoprazole in general practice in England. METHODS:In prescription-event monitoring cohort studies, data on dispensed prescriptions prescribed by general practitioners in England soon ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2125.2000.00262.x

    authors: Martin RM,Dunn NR,Freemantle S,Shakir S

    更新日期:2000-10-01 00:00:00

  • Stereoselective disposition of ibuprofen in patients with compromised renal haemodynamics.

    abstract::1. The primary aim of this study was to assess the impact of renal haemodynamics on the pharmacokinetic behaviour of ibuprofen enantiomers. Thirty-two patients and ten age-matched healthy volunteers participated in this study. These patients had at least one of the following risk factors for cardiovascular disorders: ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1995.tb04536.x

    authors: Chen CY,Chen CS

    更新日期:1995-07-01 00:00:00

  • Weight related differences in the pharmacokinetics of abacavir in HIV-infected patients.

    abstract:AIM:To study the possible influence of patient characteristics on abacavir pharmacokinetics. METHODS:A population pharmacokinetic model for abacavir was developed using data from 188 adult patients by the use of a nonlinear mixed effects modelling method performed with NONMEM. RESULTS:Abacavir pharmacokinetics was we...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.2004.02259.x

    authors: Jullien V,Tréluyer JM,Chappuy H,Dimet J,Rey E,Dupin N,Salmon D,Pons G,Urien S

    更新日期:2005-02-01 00:00:00

  • Plasma melatonin during desmethylimipramine treatment: evidence for changes in noradrenergic transmission.

    abstract::Plasma melatonin was used to determine overall beta-adrenergic transmission through pineal neuro-effector junctions during desmethylimipramine (DMI) treatment in 10 normal subjects. Changes in plasma melatonin indicated that an initial increase in noradrenaline (NA) transmission produced by DMI was counteracted by ada...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1985.tb02717.x

    authors: Cowen PJ,Green AR,Grahame-Smith DG,Braddock LE

    更新日期:1985-06-01 00:00:00

  • Comparative effects of lisinopril and losartan on insulin sensitivity in the treatment of non diabetic hypertensive patients.

    abstract:AIMS:The aim of this study was to compare the effects of the ACE-inhibitor lisinopril and the angiotensin II receptor antagonist losartan on insulin sensitivity in the treatment of non diabetic hypertensives. METHODS:Twenty-five non diabetic subjects with mild to moderate hypertension, 11 females and 14 males, aged 44...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1046/j.1365-2125.1998.00811.x

    authors: Fogari R,Zoppi A,Corradi L,Lazzari P,Mugellini A,Lusardi P

    更新日期:1998-11-01 00:00:00

  • Integrated semi-physiological pharmacokinetic model for both sunitinib and its active metabolite SU12662.

    abstract:AIMS:Previously published pharmacokinetic (PK) models for sunitinib and its active metabolite SU12662 were based on a limited dataset or lacked important elements such as correlations between sunitinib and its metabolite. The current study aimed to develop an improved PK model that circumvented these limitations and to...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/bcp.12550

    authors: Yu H,Steeghs N,Kloth JS,de Wit D,van Hasselt JG,van Erp NP,Beijnen JH,Schellens JH,Mathijssen RH,Huitema AD

    更新日期:2015-05-01 00:00:00

  • The effect of nicardipine on pituitary hormone release in normal volunteers.

    abstract::In a double-blind, placebo-controlled, randomised, cross-over study of six healthy male subjects, the effect of nicardipine (5 mg h-1 for 3 h) on basal and stimulated pituitary hormone release was examined. Statistically significant differences between nicardipine and placebo were seen occasionally for follicle-stimul...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1111/j.1365-2125.1985.tb05147.x

    authors: Isles TE,Baty J,Dow RJ

    更新日期:1985-01-01 00:00:00

  • Sedation for gastroscopy: a comparative study of midazolam and Diazemuls in patients with and without cirrhosis.

    abstract::A double-blind controlled study comparing the effects of intravenous Diazemuls (0.15 mg kg-1) with midazolam (0.07 mg kg-1) in patients with normal liver function and with cirrhosis and portal hypertension is described. The clinical effect of the two drugs was assessed by serial tests of psychomotor function before an...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1111/j.1365-2125.1986.tb02952.x

    authors: Hamdy NA,Kennedy HJ,Nicholl J,Triger DR

    更新日期:1986-12-01 00:00:00

  • The effect of rectal ozone on the portal vein oxygenation and pharmacokinetics of propranolol in liver cirrhosis (a preliminary human study).

    abstract:AIM:The aim of this study was to investigate the effect of rectal ozone on portal vein oxygenation and the pharmacokinetic changes of propranolol in patients with liver cirrhosis. METHODS:Fifteen patients with liver cirrhosis were included They were given a fixed oral dose of propranolol 80mg on the morning of day 1 a...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.2010.03851.x

    authors: Zaky S,Fouad EA,Kotb HI

    更新日期:2011-03-01 00:00:00

  • Bioactivation of dapsone to a cytotoxic metabolite by human hepatic microsomal enzymes.

    abstract::1. Using human mononuclear leucocytes as target cells, we have investigated the bioactivation of dapsone (DDS) to a cytotoxic metabolite in the presence of microsomes from nine human livers. Values for NADPH dependent toxicity ranged from 8.8-27% (15.8 +/- 5.9%) and were similar to those for microsomes from control mi...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1989.tb03517.x

    authors: Coleman MD,Breckenridge AM,Park BK

    更新日期:1989-10-01 00:00:00

  • Salbutamol inhibits metabisulphite-induced bronchoconstriction.

    abstract::The effect of salbutamol on bronchoconstriction induced by inhaled sodium metabisulphite has been studied in 12 atopic subjects. Salbutamol (200 micrograms, 3.5 x 10(-7) M) and matched placebo were administered by identical metered dose inhaler 15 min before a dose-response to sodium metabisulphite (1.25-100 mg ml-1) ...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1111/j.1365-2125.1991.tb03967.x

    authors: Iredale MJ,Dixon CM,Ind PW

    更新日期:1991-11-01 00:00:00

  • The pharmacokinetics, antihistamine and concentration-effect relationship of ebastine in healthy subjects.

    abstract::1. The kinetics and effects of ebastine 10 and 50 mg were studied after oral dosing in healthy subjects. 2. The parent drug was extensively metabolised during the first pass to its carboxylic acid derivative, carebastine. 3. The pharmacokinetics of carebastine were linear over the dose range studied and the terminal e...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1111/j.1365-2125.1988.tb05288.x

    authors: Vincent J,Liminana R,Meredith PA,Reid JL

    更新日期:1988-11-01 00:00:00

  • Selective effects of low doses of apomorphine on spatiotemporal contrast sensitivity in healthy volunteers: a double-blind placebo-controlled study.

    abstract::1. Apomorphine (1 and 5 micrograms kg-1) and placebo were given to nine normal volunteers, using a Latin-square design and double-blind procedures. The visual perception of static and moving patterns (static and motion contrast sensitivity) was evaluated before and 15 min after the dose administration. 2. Apomorphine ...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1111/j.1365-2125.1991.tb03950.x

    authors: Blin O,Mestre D,Masson G,Serratrice G

    更新日期:1991-11-01 00:00:00

  • Effect of maximal hydration on the renal responses to pretreatment with nonsteroidal anti-inflammatory drugs and probenecid in man.

    abstract::The renal response to a challenge of maximal water diuresis has been studied in seven subjects pretreated over 48 h with either placebo, probenecid, indomethacin or piroxicam. Probenecid did not alter the excretion of water and sodium chloride when compared with placebo responses, but increased both phosphate and urat...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1111/j.1365-2125.1988.tb03355.x

    authors: Dixey JJ,Noormohamed FH,Lant AF,Brewerton DA

    更新日期:1988-05-01 00:00:00

  • Clinical metabolomics paves the way towards future healthcare strategies.

    abstract::Metabolomics is recognized as a powerful top-down system biological approach to understand genetic-environment-health paradigms paving new avenues to identify clinically relevant biomarkers. It is nowadays commonly used in clinical applications shedding new light on physiological regulatory processes of complex mammal...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2125.2012.04216.x

    authors: Collino S,Martin FP,Rezzi S

    更新日期:2013-03-01 00:00:00

  • Developmental pharmacokinetics of propylene glycol in preterm and term neonates.

    abstract:AIM:Propylene glycol (PG) is often applied as an excipient in drug formulations. As these formulations may also be used in neonates, the aim of this study was to characterize the pharmacokinetics of propylene glycol, co-administered intravenously with paracetamol (800 mg PG/1000 mg paracetamol) or phenobarbital (700 mg...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.2012.04312.x

    authors: De Cock RF,Knibbe CA,Kulo A,de Hoon J,Verbesselt R,Danhof M,Allegaert K

    更新日期:2013-01-01 00:00:00

  • Lisinopril: dose-peak effect relationship in essential hypertension.

    abstract::1. The dose-peak effect relationship of lisinopril was evaluated in a double-blind, parallel study in 83 patients with mild to moderate essential hypertension (supine diastolic blood pressure = 95-115 mm Hg). 2. After a 4 week placebo washout, patients were randomly assigned to one of four treatments: lisinopril 2.5, ...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1111/j.1365-2125.1988.tb03342.x

    authors: Cirillo VJ,Gomez HJ,Salonen J,Salonen R,Rissanen V,Bolognese JA,Nyberg R,Kristianson K

    更新日期:1988-05-01 00:00:00

  • Bioavailability of temazepam in soft gelatin capsules.

    abstract::1 Healthy volunteers received single doses of temazepam 30 mg in conventional gelatin capsules, suppositories or in solution. They experienced marked sedation and sleepiness. The onset of sleepiness was prompt after the administration of the solution; this latter showed the fastest absorption and gave the highest peak...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1979.tb00452.x

    authors: Fuccella LM

    更新日期:1979-01-01 00:00:00

  • Erythropoietin doping in cycling: lack of evidence for efficacy and a negative risk-benefit.

    abstract::Imagine a medicine that is expected to have very limited effects based upon knowledge of its pharmacology and (patho)physiology and that is studied in the wrong population, with low-quality studies that use a surrogate end-point that relates to the clinical end-point in a partial manner at most. Such a medicine would ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/bcp.12034

    authors: Heuberger JA,Cohen Tervaert JM,Schepers FM,Vliegenthart AD,Rotmans JI,Daniels JM,Burggraaf J,Cohen AF

    更新日期:2013-06-01 00:00:00

  • The pharmacokinetics of methotrexate and its 7-hydroxy metabolite in patients with rheumatoid arthritis.

    abstract::1. The pharmacokinetics of MTX and its 7-hydroxy metabolite (7-OHMTX) were investigated in nine patients with rheumatoid arthritis (RA). Each patient received 15 mg MTX i.v., i.m. and p.o. after an overnight fast in a randomized cross-over design. The plasma concentrations of MTX and 7-OHMTX were measured over 7 days ...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1111/j.1365-2125.1993.tb04158.x

    authors: Seideman P,Beck O,Eksborg S,Wennberg M

    更新日期:1993-04-01 00:00:00