Abstract:
PURPOSE:Olaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for ovarian and metastatic breast cancer. Increased serum creatinine levels have been observed in patients taking olaparib, but the underlying mechanism is unknown. This study aimed to investigate if patients receiving olaparib have increased creatinine levels during olaparib treatment and whether this actually relates to a declined glomerular filtration rate (GFR). METHODS:We retrospectively identified patients using olaparib at the Netherlands Cancer Institute - Antoni van Leeuwenhoek (NKI-AVL) from 2012 until 2020. Patients with at least one plasma or serum sample available at baseline/off treatment and during olaparib treatment were included. Cystatin C levels were measured, creatinine levels were available and renal function was determined by calculating the estimated glomerular filtration rate (eGFR) using the Creatinine Equation (CKD-EPI 2009) and the Cystatin C Equation (CKD-EPI 2012). RESULTS:In total, 66 patients were included. Olaparib treatment was associated with a 14% increase in median creatinine from 72 (inter quartile range (IQR): 22) μmol/L before/off treatment to 82 (IQR: 20) μmol/L during treatment (p < 0.001) and a 13% decrease in median creatinine-derived eGFR from 86 (IQR: 26) mL/min/1.73 m2 before/off treatment to 75 (IQR: 29) mL/min/1.73 m2 during treatment (p < 0.001). Olaparib treatment had no significant effect on median cystatin C levels (p = 0.520) and the median cystatin C-derived eGFR (p = 0.918). CONCLUSIONS:This study demonstrates that olaparib likely causes inhibition of renal transporters leading to a reversible and dose-dependent increase in creatinine and does not affect GFR, since the median cystatin C-derived eGFR was comparable before/off treatment and during treatment of olaparib. Using the creatinine-derived eGFR can give an underestimation of GFR in patients taking olaparib. Therefore, an alternative renal marker such as cystatin C should be used to accurately calculate eGFR in patients taking olaparib.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Bruin MAC,Korse CM,van Wijnen B,de Jong VMT,Linn SC,van Triest B,Rosing H,Beijnen JH,van den Broek D,Huitema ADRdoi
10.1007/s00228-020-03070-0subject
Has Abstractpub_date
2021-02-01 00:00:00pages
179-188issue
2eissn
0031-6970issn
1432-1041pii
10.1007/s00228-020-03070-0journal_volume
77pub_type
杂志文章abstract::A single dose of 60 mg trimetazidine (the normal daily dose) improved exercise capacity in angina pectoris, as reflected by an increase in the duration of exercise, total work performed, and improvement in ECG signs of ischaemia. All these effects occurred without any detectable chronotropic or vasomotor effect. The i...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00544569
更新日期:1987-01-01 00:00:00
abstract::A randomized, single-blind trial of repeated intravenous infusion of Brinase was carried out in 70 petients with severe chronic limb ischemia, who were candidates for lumbar sympathectomy or amputation. The enzyme caused s significant increase in calf and ankle pressure index. At six months follow-up, the clinical res...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00562056
更新日期:1979-09-01 00:00:00
abstract:PURPOSE:To investigate pharmacokinetics (PK) of encapsulated CPT-11, released CPT-11 and the active metabolite SN-38 following administration of IHL-305 and to identify factors that may influence IHL-305 PK. METHODS:Plasma samples from 39 patients with solid tumors were collected in a phase I study. IHL-305 was admini...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-013-1580-y
更新日期:2013-12-01 00:00:00
abstract::Changes in phenytoin concentrations caused by switching valproate formulations with different absorption rates were retrospectively investigated in eleven epileptic patients receiving treatment with both drugs. Total plasma phenytoin concentrations were measured before and after a standard tablet of valproate was repl...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00202174
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:Bosutinib is an oral, dual Src and Abl tyrosine kinase inhibitor (TKI) approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia resistant or intolerant to prior TKI therapy. Bosutinib is primarily metabolized by cytochrome P450 (CYP) 3A4, suggesting drug interaction potential with...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-016-2108-z
更新日期:2017-01-01 00:00:00
abstract::Of 23 patients with non-insulin-dependent diabetes mellitus (NIDDM), whose fasting blood glucose had not reached less than or equal to 6.0 mmol.l-1 after 10 weeks of dietary regulation, 15, who had had a weight reduction of -2.8 kg by dietary control, did achieve a fasting blood glucose less than or equal to 6.0 mmol....
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00314924
更新日期:1992-01-01 00:00:00
abstract::Plasma levels of canrenone and 'total metabolites' after base hydrolysis were compared in young and elderly subjects following single and multiple doses of spironolactone. After the initial dose on Day 1, plasma levels of canrenone and 'total metabolites' were higher in the young than in the elderly group, and signifi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00549591
更新日期:1984-01-01 00:00:00
abstract::Prazosin is a post synaptic alpha adrenergic blocker effective in hypertension, whose hypotensive effect is unaccompanied by reflex tachycardia or hyperreninemia, nor by other evidence of increased sympathetic activity. We studied the baroreceptor reflex arc as a potential mediator of these effects. Twenty-two essenti...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00606418
更新日期:1982-01-01 00:00:00
abstract::There are many questions concerned with therapy and its application. Depending on the perspective of the study there can be several "populations" which, when considered individually, may give different, or even inconsistent conclusions. These populations are: the sick population, the therapist's target population, the...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00314951
更新日期:1991-01-01 00:00:00
abstract:OBJECTIVES:A temporal relationship between the increasing use of antibiotics and the increasing levels of antibiotic resistance has been established for Streptococcus pneumoniae. There are also data that support the presence of a geographic correlation between the level of resistance and the pattern of use among differ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-003-0724-x
更新日期:2004-04-01 00:00:00
abstract:PURPOSE:To aid prescribers in assessing a patient's risk for statin-induced myopathy (SIM), we performed a comprehensive review of currently known risk factors and calculated aggregated odds ratios for each risk factor through a meta-analysis. METHODS:This meta-analysis was done through four phases: (1) Identification...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00228-018-2482-9
更新日期:2018-09-01 00:00:00
abstract:OBJECTIVE:This study was performed to investigate whether it is possible to use saliva instead of blood usually used for therapeutic drug monitoring (TDM) of disopyramide. METHODS:Six healthy male volunteers ingested 200 mg of disopyramide base, and the disopyramide concentrations in saliva and plasma (total and unbou...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002280050250
更新日期:1997-01-01 00:00:00
abstract:PURPOSE:Tacrolimus is a commonly used immunosuppressant in solid organ transplantation recipients, but it is characterized by a narrow therapeutic range and large inter-individual variability. The purpose of this study was to establish a population pharmacokinetic (PK) model of tacrolimus and evaluate the influence of ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-012-1296-4
更新日期:2013-01-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280100366
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abstract::Plasma aspirin, salicylate and salicyluric acid concentrations were monitored in young, elderly and alcoholic subjects after ingestion of a single 1.2 g dose of soluble aspirin. The plasma aspirin, salicylate and unbound salicylate concentration-time profiles varied considerably between individual subjects. Most of th...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00543800
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abstract:OBJECTIVE:Theophylline is metabolized to 1,3-dimethyluric acid (1,3-DMU), 3-methylxanthine, and 1-methylxanthine by CYP1A2 and partly by CYP2E1. Because 1,3-DMU is the major metabolite of theophylline, the 1,3-DMU/theophylline ratio is viewed as a good indicator of theophylline metabolic clearance. Here, we investigate...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-006-0165-4
更新日期:2006-08-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-020-03036-2
更新日期:2020-11-11 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00679780
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00609885
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abstract::The bronchodilator activity and side-effects of treatment for 4 days with either 0.085, 0.170 or 0.34 mg/kg bambuterol b.i.d. (a prodrug of terbutaline) or 0.071 mg/kg terbutaline t.i.d. have been evaluated over 12 h, in a double-blind, randomized crossover trial in 19 asthmatic out-patients. Plasma terbutaline concen...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00614187
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:Fibroblast growth factor receptor 4 (FGFR4) expression has association with tumor malignancy. In thyroid cancers, FGFR4 has been reported to be characteristically expressed in aggressive thyroid tumors, such as anaplastic thyroid carcinoma (ATC). METHODS:We investigated FGFR4 expression in patients with ATC an...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-020-02842-y
更新日期:2020-05-01 00:00:00
abstract::The concentration of chlorpromazine (CPZ) in hair was measured to demonstrate its value as an index of individual dosage history and compliance. An animal study using pigmented rats was conducted to confirm the dose-dependent accumulation of CPZ in hair. The concentration of CPZ in hair, newly regrown on a denuded are...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315540
更新日期:1993-01-01 00:00:00
abstract::The pharmacokinetics of ceftazidime have been investigated after single and multiple i.v. doses in 9 young healthy male volunteers and 15 elderly male patients with acute bacterial infections. All subjects had normal, age-correlated glomerular function. Distribution and elimination in young volunteers were unaffected ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00614556
更新日期:1988-01-01 00:00:00
abstract::Propranolol (P) and all of its major known metabolites were found in maternal plasma, cord plasma and neonatal plasma in 10 women at term, irrespective of the P doses administered and the time elapsed (up to 15 h) between administration of the last P dose and delivery. The ratios of cord plasma to simultaneous materna...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00607078
更新日期:1983-01-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:2020-01-01 00:00:00
abstract::The effects of metolazone on the protein binding of glibenclamide were studied. It was found that increasing metolazone concentrations up to 100 ng/ml had no significant effect on the protein binding of glibenclamide studied at 10 micrograms/ml. Metolazone is unlikely to cause a clinically significant increase in the ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00314813
更新日期:1990-01-01 00:00:00
abstract:OBJECTIVE:Lamotrigine as add-on treatment (500 mg per day) is effective in patients with refractory epilepsy, but its high cost requires a pharmacoeconomic analysis. We conducted a retrospective lifetime cost utility study in which clinical data were derived from a recent placebo-controlled clinical trial, cost-of-illn...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050402
更新日期:1998-02-01 00:00:00
abstract::The metabolism of hydralazine in a group of slow acetylator patients with the drug-induced lupus syndrome was compared with the metabolism in asymptomatic control subjects. There were no toxicologically significant difference in metabolite excretion between the groups which reached statistical significance, although t...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00556891
更新日期:1984-01-01 00:00:00
abstract:OBJECTIVE:The goal of this study was to determine the frequencies of important allelic variants of two drug targets, dipeptidyl carboxypeptidase ( DCP1) and cholesteryl ester transfer protein ( CETP), and two other drug receptors, beta-2 adrenergic receptor ( ADRB2) and 5-hydroxy tryptamine 2A receptor ( HTR2A), in the...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-002-0423-z
更新日期:2002-04-01 00:00:00