D J Touw

University of Groningen, Groningen, Groningen, Netherlands

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Publications (90)278.94 Total impact

  • Journal of Cystic Fibrosis 06/2015; 14:S49. DOI:10.1016/S1569-1993(15)30158-2 · 3.48 Impact Factor
  • Journal of Cystic Fibrosis 06/2015; 14:S26. DOI:10.1016/S1569-1993(15)30083-7 · 3.48 Impact Factor
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    European Respiratory Journal 04/2015; 46(1). DOI:10.1183/09031936.00177014 · 7.64 Impact Factor
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    ABSTRACT: The clinical effectiveness of inhaled tobramycin depends on the dose reaching the desired regions of the lungs. This study evaluates the influence of breathing mode on tobramycin lung deposition using its pharmacokinetics as surrogate for deposition. In a randomized, open-label, crossover study lung deposition in 18 adult CF patients is evaluated following inhalation of tobramycin aerosol using the I-neb nebulizer with TBM (Tidal Breathing Mode) and TIM (Target Inhalation Mode) breathing patterns. Breathing in TIM forced the patient to inhale in a slow and deep manner. Patients were categorized in three subgroups according to their lung function: ≤59%, 60-79% or ≥80% of FEV1 predicted. Blood samples were collected in order to model tobramycin pharmacokinetics. Nebulization time was recorded. Inhalation with TIM resulted in significantly higher maximum serum levels and area under the concentration-time curves (0-24h). Mean bioavailability of TIM relative to TBM was 1.53±0.41. Mean nebulization time was reduced by half with TIM. Subgroup category did not affect the results. Slow and deep inhalation of aerosolized tobramycin resulted in higher lung deposition and shorter nebulization time compared to tidal breathing, regardless of the disease severity of the CF patient. Dutch trial register number NTR3109. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
    Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 01/2015; DOI:10.1016/j.jcf.2015.01.002 · 3.48 Impact Factor
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    ABSTRACT: Background hospitalized patients with serious infections treated with aminoglycosides are at risk of developing nephrotoxicity. Previous clinical studies have shown that the pharmacokinetics of aminoglycosides in humans follow a circadian rhythm. Therefore, the time of administration could have important clinical implications with respect to the risk of developing aminoglycoside-associated nephrotoxicity in patients treated with once daily dosing regimens. Objective To examine the effect of the time period of administration on aminoglycoside exposure and the incidence of nephrotoxicity in a large population of hospitalized patients with serious infections. Setting General ward and intensive care unit of a teaching hospital. Method In this retrospective cohort study, patients treated with intravenous tobramycin or gentamicin were eligible for inclusion. Patients were divided into three groups by time of administration: morning, afternoon and night. Main outcome measure Pharmacokinetic parameters and the incidences of nephrotoxicity were compared between the morning, afternoon and evening groups. Results 310 general ward and 411 intensive care unit patients were included. No significant differences were found in patient characteristics between the morning, afternoon and night groups. The time period of administration did not affect aminoglycoside pharmacokinetics or the incidence of nephrotoxicity. Conclusion The time of administration has no effect on the pharmacokinetics or nephrotoxicity of once daily dosed aminoglycosides in hospitalized patients. Consequently, we advise aminoglycosides to be administered as soon as possible in case of (suspected) severe hospital-acquired infections and subsequent dosages to be based on therapeutic drug monitoring to optimize the efficacy/toxicity balance.
    International Journal of Clinical Pharmacy 01/2015; 37(2). DOI:10.1007/s11096-015-0066-7 · 1.35 Impact Factor
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    ABSTRACT: Introduction: The clinical application of continuous infusion (CoI) of vancomycin has gained interest in recent years. Since no international guidelines on initial dosing of vancomycin CoI exist, there is a need for methods to facilitate the switch from intermittent to continuous vancomycin dosing algorithms in clinically infected populations. Therefore, the aim of this study was to design and validate an a priori dosing schedule for CoI of vancomycin in clinical practice. Methods: A dosing table for CoI of vancomycin based on estimated glomerular filtration rate (eGFR) was developed by simulation of continuous infusion of vancomycin using pharmacokinetic (PK) software and a PK population model designed from historical within-population data in intermittently dosed patients. The target range for the first vancomycin serum concentrations drawn approximately 24 h after start of infusion' (C24) was set at 15-20 mg/L corresponding with an area under the curve (AUC) of at least 350 mg·h·L(-1). The performance of the dosing schedule was primarily assessed by describing the percentages of patients attaining the predefined target. Results: An eGFR-derived dosing schedule for CoI of vancomycin was established and implemented in clinical practice. Prospective assessment in 35 general ward and 45 intensive care unit patients showed that the C24 target was reached in 69 and 63 % and the AUC target was attained in 80 and 72 % of patients, respectively. Conclusions: An easy method to design and validate an eGFR-derived dosing algorithm for the continuous infusion of vancomycin to switch from intermittent to continuous dosing of vancomycin was developed.
    European Journal of Clinical Pharmacology 08/2014; 17(11). DOI:10.1007/s00228-014-1742-6 · 2.97 Impact Factor
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    ABSTRACT: Objectives In cystic fibrosis (CF) patients the paranasal sinuses can constitute a niche for bacteria, which can migrate to the lungs. Nasal administration of antibiotics may be effective, but safety of this treatment has to be established first. The objective of this study was to investigate the systemic absorption of nasally administered tobramycin, colistin (administered as colistin sulfomethate sodium; CMS) and a combination of both drugs using systemic absorption as surrogate for safety. In addition, tolerability of the nasal irrigations was examined.
    Journal of Antimicrobial Chemotherapy 07/2014; 69(11). DOI:10.1093/jac/dku239 · 5.31 Impact Factor
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    ABSTRACT: Objectives: Since 2007 the Dutch Association for Quality Assessment in Therapeutic Drug Monitoring (KKGT) has organized an international interlaboratory proficiency testing (PT) programme for measurement of antifungal drugs in plasma. We describe the 5 year results of the laboratories' performance. Methods: Twice a year, laboratories received a set of blind plasma samples containing low or high concentrations of fluconazole, itraconazole, hydroxyitraconazole, posaconazole, voriconazole and flucytosine. Participating laboratories were asked to report their results within 6 weeks after dispatch and provide details of their analytical methods. Results deviating >20% from the weighed-in concentration were considered inaccurate. Four-way ANOVA was performed to assess the effect of antifungal drug measured, concentration, analytical method and performing laboratory on the absolute inaccuracy. In 2012, a questionnaire based on the CLSI guidelines was dispatched with the request to provide input on sources of error. Results: Fifty-seven laboratories (13 countries) reported 2251 results (287 fluconazole, 451 itraconazole, 348 hydroxyitraconazole, 402 posaconazole, 652 voriconazole and 111 flucytosine) in 5 years. Analyses were performed using HPLC (55.0%), LC-MS(/MS) (43.4%), UPLC (1.4%) or GC-MS (0.2%). Overall, 432 (19.2%) analyses were inaccurate. The performing laboratory was the only factor clearly associated with inaccuracies. The questionnaire results indicated that laboratories encounter significant problems analysing low concentrations (15.4% of all inaccuracies). Conclusions: Results of the PT programme suggest that one out of five measurements is inaccurate. The performing laboratory is the main determinant of inaccuracy, suggesting that internal quality assurance is pivotal in preventing inaccuracies, irrespective of the antifungal drug measured, concentration and analytical equipment.
    Journal of Antimicrobial Chemotherapy 07/2014; 69(11). DOI:10.1093/jac/dku242 · 5.31 Impact Factor
  • Journal of Cystic Fibrosis 06/2014; 13:S57. DOI:10.1016/S1569-1993(14)60178-8 · 3.48 Impact Factor
  • Journal of Antimicrobial Chemotherapy 05/2014; 69(9). DOI:10.1093/jac/dku175 · 5.31 Impact Factor
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    ABSTRACT: Background:Ertapenem, a carbapenem, relies on time-dependant killing. Therapeutic drug monitoring (TDM) should be considered, when used in specific populations, to achieve optimal bactericidal activity and optimize drug-dosing regimens. No validated LC-MS/MS method has been reported using deuterated ertapenem as internal standard. A new simple and robust LC-MS/MS method using a quadruple mass spectrometer was developed for analysis of ertapenem in human plasma, using deuterated ertapenem as internal standard. The calibration curve was linear over a range of 0.1 (LLOQ) to 125 mg/L. The calculated accuracy ranged from -2.4 % to 10.3%. Within-run CV ranged from 2.7 % to 11.8% and between-run CV ranged from 0 % to 8.4%. Freeze-thaw stability biased between -3.3% and 0.1%. Storage of QC samples for 96h at 4°C differed -4.3 to 5.6%, storage at room temperature for 24h, biased from -10.7% to -14.8% and storage in the autosampler biased between -2.9% and -10.0%. A simple LC-MS/MS method to quantify ertapenem in human plasma using deuterated ertapenem as internal standard has been validated. This method can be used in pharmacokinetic studies and in clinical studies by performing TDM.
    Antimicrobial Agents and Chemotherapy 04/2014; 58(6). DOI:10.1128/AAC.00025-14 · 4.48 Impact Factor
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    Journal of Cystic Fibrosis 06/2013; 12:S98. DOI:10.1016/S1569-1993(13)60338-0 · 3.48 Impact Factor
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    Journal of Cystic Fibrosis 06/2013; 12:S66. DOI:10.1016/S1569-1993(13)60213-1 · 3.48 Impact Factor
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    ABSTRACT: : Observational data sets can be used for population pharmacokinetic (PK) modeling. However, these data sets are generally less precisely recorded than experimental data sets. This article aims to investigate the influence of erroneous records on population PK modeling and individual maximum a posteriori Bayesian (MAPB) estimation. : A total of 1123 patient records of neonates who were administered vancomycin were used for population PK modeling by iterative 2-stage Bayesian (ITSB) analysis. Cut-off values for weighted residuals were tested for exclusion of records from the analysis. A simulation study was performed to assess the influence of erroneous records on population modeling and individual MAPB estimation. Also the cut-off values for weighted residuals were tested in the simulation study. : Errors in registration have limited the influence on outcomes of population PK modeling but can have detrimental effects on individual MAPB estimation. A population PK model created from a data set with many registration errors has little influence on subsequent MAPB estimates for precisely recorded data. A weighted residual value of 2 for concentration measurements has good discriminative power for identification of erroneous records. : ITSB analysis and its individual estimates are hardly affected by most registration errors. Large registration errors can be detected by weighted residuals of concentration.
    Therapeutic drug monitoring 07/2012; 34(5):526-34. DOI:10.1097/FTD.0b013e3182616937 · 2.38 Impact Factor
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    ABSTRACT: Azithromycin maintenance therapy results in improvement of respiratory function in patients with cystic fibrosis (CF). In azithromycin maintenance therapy, several dosing schemes are applied. In this review, we combine current knowledge about azithromycin pharmacokinetics with the dosing schedules used in clinical trials in order to come to a dosing advise which could be generally applicable. We used data from a recently updated Cochrane meta analysis (2011), the reports of clinical trials and pharmacokinetic studies. Based on these data, it was concluded that a dose level of 22-30 mg/kg/week is the lowest dose level with proven efficacy. Due to the extended half-life in patients with CF, the weekly dose of azithromycin can be divided in one to seven dosing moments, depending on patient preference and gastro-intestinal tolerance. No important side effects or interactions with other CF-related drugs have been documented so far.
    Pediatric Pulmonology 07/2012; 47(7):658-65. DOI:10.1002/ppul.21620 · 2.70 Impact Factor
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    ABSTRACT: Esomeprazole and rabeprazole are metabolised in the liver by means of the CYP2C19 enzyme, which has several functional genetic polymorphisms. Among Caucasians, 70% of the population has a fast metaboliser phenotype, 25-30% an intermediate and 2-5% a slow metaboliser phenotype. It is unknown whether different PPIs are affected to the same extent by these phenotypic differences. To compare the acid-inhibitory effects of esomeprazole 40 mg and rabeprazole 20 mg in relation to CYP2C19 genotype and pharmacokinetics. Eighteen healthy Helicobacter pylori-negative Caucasian subjects with CYP2C19*2-*6 and *17 genotype were included in a randomised investigator-blinded crossover study with esomeprazole 40 mg and rabeprazole 20 mg. Intragastric 24-h pH-monitoring was performed on days 0, 1 and 5 of oral dosing. Onset of acid inhibition during the first 4 h after administration did not differ significantly between PPIs. During the upright period, the proportion of time with pH >4 was significantly higher with esomeprazole compared to rabeprazole (52.2 vs. 40.3%, P = 0.003). At day 1 and 5, acid inhibition was significantly greater with esomeprazole than with rabeprazole (median intragastric pH: day 1: 3.7 vs. 3.0, P = 0.008; day 5: 4.7 vs. 3.8, P < 0.001; percentage of time pH >4: day 1: 45 vs. 39%, P = 0.054; day 5: 65 vs. 48%, P < 0.001). Differences in acid inhibition between wt/wt and wt/*2 genotype were significant for both PPIs. Once-daily dosing with esomeprazole 40 mg provides a more effective and faster acid-inhibitory effect than rabeprazole 20 mg. The acid-inhibitory effect of esomeprazole and rabeprazole are both influenced by CYP2C19 polymorphism.
    Alimentary Pharmacology & Therapeutics 02/2012; 35(7):810-8. DOI:10.1111/j.1365-2036.2012.05014.x · 5.73 Impact Factor
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    ABSTRACT: Currently, there are very few guidelines linking the results of pharmacogenetic tests to specific therapeutic recommendations. Therefore, the Royal Dutch Association for the Advancement of Pharmacy established the Pharmacogenetics Working Group with the objective of developing pharmacogenetics-based therapeutic (dose) recommendations. After systematic review of the literature, recommendations were developed for 53 drugs associated with genes coding for CYP2D6, CYP2C19, CYP2C9, thiopurine-S-methyltransferase (TPMT), dihydropyrimidine dehydrogenase (DPD), vitamin K epoxide reductase (VKORC1), uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), HLA-B44, HLA-B*5701, CYP3A5, and factor V Leiden (FVL).
    Clinical Pharmacology &#38 Therapeutics 03/2011; 89(5):662-73. DOI:10.1038/clpt.2011.34 · 7.90 Impact Factor
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    ABSTRACT: Maximum a posteriori Bayesian (MAPB) pharmacokinetic parameter estimation is an accurate and flexible method of estimating individual pharmacokinetic parameters using individual blood concentrations and prior information. In the past decade, many studies have developed optimal sampling strategies to estimate pharmacokinetic parameters as accurately as possible using either multiple regression analysis or MAPB estimation. This has been done for many drugs, especially immunosuppressants and anticancer agents. Methods of development for optimal sampling strategies (OSS) are diverse and heterogeneous. This review provides a comprehensive overview of OSS development methodology using MAPB pharmacokinetic parameter estimation, determines the transferability of published OSSs, and compares sampling strategies determined by MAPB estimation and multiple regression analysis. OSS development has the following components: 1) prior distributions; 2) reference value determination; 3) optimal sampling time identification; and 4) validation of the OSS. Published OSSs often lack all data necessary for the OSS to be clinically transferable. MAPB estimation is similar to multiple regression analysis in terms of predictive performance but superior in flexibility.
    Therapeutic drug monitoring 03/2011; 33(2):133-46. DOI:10.1097/FTD.0b013e31820f40f8 · 2.38 Impact Factor
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    ABSTRACT: Esomeprazole and pantoprazole are metabolized in the liver and the polymorphic CYP2C19 enzyme is involved in that process. This genetic polymorphism determines fast (70% of Caucasians), intermediate (25-30% of Caucasians) and slow (2-5% of Caucasians) metabolism of PPIs. To compare the acid-inhibitory effects of esomeprazole 40 mg and pantoprazole 40 mg at 4, 24 and 120 h after oral administration in relation to CYP2C19 genotype and pharmacokinetics. CYP2C19*2, *3, *4, *5 and *17 genotypes were determined in healthy Helicobacter pylori-negative Caucasian subjects. 7 wt/wt, 7 wt/*2, 2 wt/*17, 2 *2/*17 and 1 *2/*2 were included in a randomized investigator-blinded cross-over study with esomeprazole 40 mg and pantoprazole 40 mg. Intragastric 24-h pH-monitoring was performed on days 0, 1 and 5 of oral dosing. A total of 19 subjects (mean age 24 years, 7 male) completed the study. At day 1 and 5, acid-inhibition with esomeprazole was significantly greater and faster than with pantoprazole. Differences in acid-inhibition and pharmacokinetics between wt/wt and wt/*2 genotype were significant for pantoprazole at day 1 and 5. Esomeprazole provides acid-inhibition faster than and superior to pantoprazole after single and repeated administration. The acid-inhibitory effect and the kinetics of pantoprazole are influenced by CYP2C19 genotype.
    Alimentary Pharmacology & Therapeutics 09/2009; 31(1):150-9. DOI:10.1111/j.1365-2036.2009.04150.x · 5.73 Impact Factor
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    ABSTRACT: Recent position papers addressing the profession of clinical pharmacology have expressed concerns about the decline of interest in the field among clinicians and medical educators in the United Kingdom and other Western countries, whether clinical pharmacology is actually therapeutics, and whether the profession should be limited to physicians. The Dutch Society for Clinical Pharmacology and Biopharmacy offers answers to these questions and presents a new model for clinical pharmacology.Clinical Pharmacology & Therapeutics (2009); 85, 4, 366-368 doi:10.1038/clpt.2008.148
    Clinical Pharmacology &#38 Therapeutics 05/2009; 85(4). DOI:10.1038/clpt.2008.148 · 7.90 Impact Factor

Publication Stats

2k Citations
278.94 Total Impact Points


  • 2014–2015
    • University of Groningen
      • Department of Clinical Pharmacology
      Groningen, Groningen, Netherlands
  • 1993–2014
    • HagaZiekenhuis van Den Haag
      's-Gravenhage, South Holland, Netherlands
  • 2002–2011
    • Stichting Apotheek der Haarlemse Ziekenhuizen
      Haarlem, North Holland, Netherlands
  • 2006
    • Medisch Spectrum Twente
      Enschede, Overijssel, Netherlands
  • 2001
    • VU University Medical Center
      • Department of Neonatology
      Amsterdamo, North Holland, Netherlands
  • 1996–2001
    • VU University Amsterdam
      • Department of Medical Microbiology and Infection Control
      Amsterdamo, North Holland, Netherlands
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Pharmacy
      Amsterdamo, North Holland, Netherlands
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands
  • 1994
    • Leiden University
      Leyden, South Holland, Netherlands