Abstract:
AIMS:Azathioprine, mercaptopurine and thioguanine are commonly used to treat autoimmune disorders, leukaemia and solid organ transplantation. However, azathiopurine and its metabolites can also cause adverse reactions such as myelosuppression. These manifestations may be attributed to polymorphisms or mutations in the thiopurine methyltransferase (TPMT) gene that might result in low TPMT enzyme activity. Our aim was to investigate if azathioprine-related myelosuppression is associated with TPMT polymorphism, which in turn affects its enzyme activity. METHODS:A 61-year-old Chinese man with severe atopic eczema developed moderate myelosuppression with standard doses of azathioprine. His TPMT activity was measured using radiochemical assay. Genotyping of TPMT *3C, *3A and *6 were screened using polymerase chain reaction-restriction fragment length polymorphism. Novel mutation was detected by sequencing. Family studies of his three other siblings were performed. RESULTS:After 4 weeks of azathioprine treatment, the patient's white blood cells and absolute neutrophil count dropped by 40-45%. He was then taken off azathioprine, and blood counts returned to normal. TPMT activity test showed intermediate levels of 9.1 nmol h(-1) ml(-1) peripheral red blood cells (pRBC). Resequencing of the TPMT gene revealed a missense mutation Phe-->Leu at 208 aa position in exon 9 (ss105107120). Two of his three siblings were heterozygous for 208F-->L, which accounts for the decreased enzyme activity (brother 8.9 nmol h(-1) ml(-1) pRBC, sister 8.8 nmol h(-1) ml(-1) pRBC). The remaining sibling had wild-type allele with normal enzyme activity. Screening of 100 normal healthy Chinese subjects did not reveal any individual with this mutation. CONCLUSION:We report a novel mutation TPMT*26 (208F-->L) associated with a decrease in TPMT enzyme activity.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Kham SK,Soh CK,Aw DC,Yeoh AEdoi
10.1111/j.1365-2125.2009.03405.xsubject
Has Abstractpub_date
2009-07-01 00:00:00pages
120-3issue
1eissn
0306-5251issn
1365-2125pii
BCP3405journal_volume
68pub_type
杂志文章abstract::1 Thirty-six patients with various neurological diseases or symptoms received single intravenous doses of either cimetidine 400 mg (n = 19) or oxmetidine 200 mg (n = 17), 15 or 60 min before a diagnostic lumbar puncture. 2 In the 15 min CSF samples concentrations of cimetidine were detectable but not measurable in 5 a...
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.1365-2125.1982.tb02042.x
更新日期:1982-12-01 00:00:00
abstract:AIMS:A multistudy analysis of cediranib, a potent, selective inhibitor of all three vascular endothelial growth factor receptors (VEGFR-1, -2 and -3), was conducted to establish population exposure-safety models for the relationship of cediranib exposure to the safety endpoints, diastolic and systolic blood pressure (D...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13495
更新日期:2018-04-01 00:00:00
abstract::Regulatory science underpins the objective evaluation of medicinal products. It is therefore imperative that regulatory science and expertise remain at the cutting edge so that innovations of ever-increasing complexity are translated safely and swiftly into effective, high-quality therapies. We undertook a comprehensi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14099
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Develop a translational assay of Transient Receptor Potential Ankyrin 1 (TRPA1) activity for use as a preclinical and clinical biomarker. EXPERIMENTAL APPROACH:Allyl isothiocyanate (AITC), capsaicin or citric acid were applied to ears of wildtype and Trpa1-knock out (Trpa1 KO) rats, and changes ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14370
更新日期:2021-01-01 00:00:00
abstract::1 Evidence concerning the convulsant effects of non-monoamine oxidase inhibitor antidepressant drugs has been reviewed. 2 Mianserin is convulsant in therapeutic doses but seizures have not been reported following overdose. 3 The convulsant effects of mianserin are probably no greater than for other non-monoamine oxida...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb05878.x
更新日期:1983-01-01 00:00:00
abstract:AIMS:Canagliflozin is a recently approved drug for use in the treatment of type 2 diabetes. The potential for canagliflozin to cause clinical drug-drug interactions (DDIs) was assessed. METHODS:DDI potential of canagliflozin was investigated using in vitro test systems containing drug metabolizing enzymes or transport...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13186
更新日期:2017-05-01 00:00:00
abstract::The disposition of mexiletine has been studied in five subjects on two occasions with urine pH controlled at 5.0 and at 8.0. With acid urine total plasma clearance was similar in all subjects (462 to 497 ml min-1) and the plasma half-life ranged from 3.8 to 9.2 h (mean 6.7 h). With alkaline urine the total plasma clea...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb02162.x
更新日期:1983-09-01 00:00:00
abstract::1 Six previously untreated emergency admissions to hospital with severe hypertension were given oral treatment with labetalol. 2 Pre-treatment diastolic BP exceeded 130 mmHg, and clinical evidence of either accelerated hypertension or encephalopathy was present. 3 Hypotensive response after treatment followed two patt...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract:AIMS:To investigate the effect of multiple oral dose treatment with the endothelin receptor antagonist bosentan on the pharmacokinetics of digoxin in healthy subjects. METHODS:This was an open-label, randomized, two-way crossover study in 18 evaluable young male subjects. They received, on two occasions which were sep...
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.1365-2125.1999.00946.x
更新日期:1999-06-01 00:00:00
abstract:AIMS:To investigate the relationships between pretreatment folate concentrations, MTX pharmacokinetics and acute toxicities following high dose methotrexate (HD MTX) therapy. METHODS:MTX and its major extracellular metabolite 7-OH-MTX were measured in eight serum samples per HD MTX cycle in 65 consecutive osteosarcoma...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2011.04054.x
更新日期:2012-01-01 00:00:00
abstract::Highly active antiretroviral therapy is recommended for HIV-infected pregnant women to prevent mother-to-child transmission. The specific physiological background induced by pregnancy leads to significant changes in maternal pharmacokinetics, suggesting potential variability in plasma concentrations of antiretrovirals...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2008.03220.x
更新日期:2008-08-01 00:00:00
abstract:BACKGROUND:Maraviroc, a noncompetitive antagonist of the CCR5 coreceptor, was recently approved in the USA as a treatment of HIV infection. For antiretroviral agents that target the virus, antiviral effect can be related to some extent to plasma drug concentrations. For CCR5 antagonists that target the host cells, rece...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,meta分析
doi:10.1111/j.1365-2125.2008.03140.x
更新日期:2008-04-01 00:00:00
abstract::Adopted guidelines reflect a harmonised European approach to a specific scientific issue and should reflect the most recent scientific knowledge. However, whilst EU regulations are mandatory for all member states and EU directives must be followed by national laws in line with the directive, EMA guidelines do not have...
journal_title:British journal of clinical pharmacology
pub_type:
doi:10.1111/bcp.13883
更新日期:2019-04-01 00:00:00
abstract:AIM:To assess the effect of Schisandra sphenanthera extract (SchE) on the pharmacokinetics of tacrolimus in healthy volunteers. METHODS:Twelve healthy male volunteers were orally treated with SchE, three capsules twice daily for 13 days. Pharmacokinetic investigations of oral tacrolimus administration at 2 mg were per...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2007.02922.x
更新日期:2007-10-01 00:00:00
abstract::1. Studies using human liver microsomes and six recombinant human CYP isoforms (i.e. CYP1A2, 2A6, 2B6, 2D6, 2E1 and 3A4) were performed to identify the cytochrome P450 (CYP) isoform(s) involved in the ring 4-hydroxylation and side-chain N-desisopropylation of propranolol enantiomers in humans. 2. alpha-Naphthoflavone ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1995.tb04472.x
更新日期:1995-04-01 00:00:00
abstract:AIMS:Therapeutic drug monitoring of infliximab can guide clinical decisions in patients with loss of response and in those who can benefit from a de-intensification. The aim of this study was to determine the impact of therapeutic drug monitoring combined with Bayesian forecasting methodology on clinical response in a ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14410
更新日期:2020-06-03 00:00:00
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
更新日期:2004-11-01 00:00:00
abstract:AIMS:Ward physicians hold key positions in the course of efforts to reduce drug expenditures in hospitals. This study evaluated the knowledge of German hospital physicians with respect to the daily therapeutic costs of 21 frequently used drugs. METHODS:A questionnaire survey was carried out among 168 ward physicians f...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2001.01336.x
更新日期:2001-04-01 00:00:00
abstract::1 Theories linking 5-hydroxytryptamine (5-HT) with depression are briefly reviewed. The various experimental strategies adopted to investigate this relationship, examination of autopsy data, CSF metabolite data, 5-HT re-uptake patterns in human blood platelets and imipramine binding studies in human platelets, are dis...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb02130.x
更新日期:1983-01-01 00:00:00
abstract:AIMS:Although cysteamine was first used in the treatment of cystinosis in 1976 and approved by the FDA as cysteamine bitartrate (Cystagon) in 1994, surprisingly little pharmacological data are available for this compound. Cysteamine and its related drugs are currently being evaluated for the treatment of Huntington's a...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2006.02734.x
更新日期:2007-01-01 00:00:00
abstract:AIMS:Mycophenolic acid (MPA) suppresses lymphocyte proliferation through inosine monophosphate dehydrogenase (IMPDH) inhibition. Two formulations have been approved: mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS). Pantoprazole (PAN) inhibits gastric acid secretion, which may alter MPA expo...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.12664
更新日期:2015-11-01 00:00:00
abstract:AIMS:Roux-en-Y gastric bypass (RYGB) alters the anatomical structure of the gastrointestinal tract, which can result in alterations in drug disposition. The aim of the present study was to evaluate the oral disposition of two compounds belonging to the Biopharmaceutical Classification System Class II - fenofibrate (bil...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/bcp.13054
更新日期:2016-11-01 00:00:00
abstract::When using biopsy pathology in clinical pharmacology to assess drug efficacy in the gastrointestinal tract, a number of questions must be answered: Is the biopsy necessary or more effective than macroscopic views by endoscopy? Can we extract maximal information from the specimen? Are there surrogate serum or other mar...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2125.2003.01981.x
更新日期:2003-11-01 00:00:00
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
更新日期:1986-12-01 00:00:00
abstract::1 The effect of labetalol has been assessed in an open clinical trial in 19 patients with sub-optimal control of blood pressure on other therapy, and in a placebo-controlled cross-over study. Most patients were taking a diuretic before the trial and they continued to do so during the trial. 2 In the open trial, labeta...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1976-08-01 00:00:00
abstract:AIMS:To characterize milk/plasma (M/P) ratio and infant dose, for venlafaxine (V) and its O-desmethyl metabolite (ODV), in breastfeeding women taking venlafaxine for the treatment of depression, and to determine the plasma concentration and effects of these drugs in their infants. METHODS:Six women (mean age 34.5 year...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.0306-5251.2001.01518.x
更新日期:2002-01-01 00:00:00
abstract:AIM:To examine the predictive value of gene polymorphisms potentially linked to toxicity, clinical response, time to progression and overall survival, following cetuximab-tegafur-uracil (UFT)-irinotecan therapy. METHODS:Fifty-two patients with advanced colorectal cancer were enrolled in an ancillary pharmacogenetic st...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2011.04141.x
更新日期:2012-05-01 00:00:00
abstract::Ten healthy normal volunteers received an intravenous infusion of erythromycin lactobionate over 60 min to a total dose of 800 mg (n = 9), and 524 mg (n = 1). Blood samples were collected at 10 min intervals for 100 min and gastric contents aspirated, via a nasogastric tube, from pre-dose to 105 min after start of inf...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1986.tb05193.x
更新日期:1986-03-01 00:00:00
abstract::1 The effects of oxprenolol 80 mg and propranolol 80 mg on resting forearm blood flow (RFBF) and skin temperature were compared in seven normotensive subjects, for 4 h after an oral dose. 2 There was a significant fall of RFBF after propranolol (mean +/- s.e. mean 0.74 +/- 0.24 ml 100 g-1 min-1) compared to a smaller ...
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.1365-2125.1981.tb01154.x
更新日期:1981-05-01 00:00:00
abstract::1. Six healthy volunteers received single doses of either nomifensine 100 mg, nomifensine 50 mg or placebo at weekly intervals in a randomized double-blind crossover study. 2. Subjects were subjected to a simulated test of car driving at night. 3. Testing lasted about 1.5 h and consisted of measuring responses to ligh...
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.1365-2125.1977.tb05748.x
更新日期:1977-01-01 00:00:00