Farmaceutisch onderzoek

872 artikelen

21 feb 2020

Geneesmiddelen als oorzaak van heropname na ontslag uit het ziekenhuis: verschil in inzicht tussen patiënt en zorgverlener

  • Rubriek:
    Referaat
  • Identificatie:
    2020;5:e1700
  • Auteur(s):
    Sander D. Borgsteede

Geneesmiddelen als oorzaak van heropname na ontslag uit het ziekenhuis: verschil in inzicht tussen patiënt en zorgverlener

13 feb 2020

Chronisch gebruik van protonpompremmers en verlaagde ijzerstatus bij patiënten met een niertransplantaat

  • Rubriek:
    Referaat
  • Identificatie:
    2020;5:e1696
  • Auteur(s):
    André Wieringa

Chronisch gebruik van protonpompremmers en verlaagde ijzerstatus bij patiënten met een niertransplantaat

04 feb 2020

Verbeterde overleving door triple-therapie in BRAF-V600E-gemuteerde colorectale kanker

  • Rubriek:
    Referaat
  • Identificatie:
    2020;5:e1695
  • Auteur(s):
    André Wieringa

Verbeterde overleving door triple-therapie in BRAF-V600E-gemuteerde colorectale kanker

30 jan 2020

De effectiviteit van medicatiebeoordeling op het aantal geneesmiddelgerelateerde problemen bij cardiologische polikliniekpatiënten

  • Rubriek:
    Referaat
  • Identificatie:
    2020;5:e1698
  • Auteur(s):
    Bob Wilffert

De effectiviteit van medicatiebeoordeling op het aantal geneesmiddelgerelateerde problemen bij cardiologische polikliniekpatiënten

24 jan 2020

Dankbetuiging 2019

  • Rubriek:
    Redactioneel
  • Identificatie:
    2020;5:e1699
  • Auteur(s):
    Redactiebureau NPFO

Dankbetuiging 2019

15 jan 2020

Invloed van het genotype van P-glycoproteïne op de werkzaamheid van paroxetine

  • Rubriek:
    Referaat
  • Identificatie:
    2020;5:e1697
  • Auteur(s):
    Bob Wilffert

Invloed van het genotype van P-glycoproteïne op de werkzaamheid van paroxetine

07 jan 2020

Hoeveel wordt verspild als patiënten stoppen met orale oncolytica of biologicals?

  • Rubriek:
    Referaat
  • Identificatie:
    2020;5:e1692
  • Auteur(s):
    Lonneke Timmers

Hoeveel wordt verspild als patiënten stoppen met orale oncolytica of biologicals?

23 dec 2019

Het positieve effect van klinische beslisregels getoond op het moment van voorschrijven

  • Rubriek:
    Oorspronkelijk artikel
  • Identificatie:
    2019;4:a1717
  • Auteur(s):
    Matthijs L. Becker ab*, Fatih Baypinar a, Marieke Pereboom ab, Soufiane Lilih c, Hylke Jan Kingma ab en Ruud T.M. van der Hoeven ab

Het positieve effect van klinische beslisregels getoond op het moment van voorschrijven

The positive effect of clinical decision support shown at the time of prescribing

BACKGROUND

Clinical decision support system (CDSS) should help healthcare providers to make better decisions. For optimal performance, a CDSS uses algorithms taking various factors in consideration. For pharmacy practice, a CDSS often generates a patient list that is reviewed by a pharmacist and the physician is contacted in case of a clinically relevant signal. In our hospital we implemented five algorithms that alert the physician directly at the time of prescribing to treat the patient in line with the guidelines.

OBJECTIVE

To evaluate the effect of implementation of algorithms for medication surveillance shown directly to the physician at the time of prescribing.

DESIGN

Prospective intervention study.

METHODS

We analyzed the change in treatments in line with the guidelines and the percentage of correct follow-up after the advice was shown. We examined the implementation of five algorithms. These were the algorithms for gastric protection, methotrexate, vitamin D, hyponatremia and therapeutic drug monitoring of aminoglycosides and vancomycin.

RESULTS

For all algorithms the percentage of treatments in line with the guidelines increased significantly. The percentage of increase varied from 11 to 36% and in three of the five CDSSs the percentage was above 80% after implementation. For the algorithm gastric protection, the advice was accepted in 45% of all signals versus 4.3% in case of the classical drug-drug interaction signals.

CONCLUSION

Algorithms for medication surveillance that are shown to the physician at the time of prescribing increase the compliance with the guidelines.

20 dec 2019

VKA-beleid in het DOAC-tijdperk: fenprocoumon ten opzichte van acenocoumarol

  • Rubriek:
    Korte bijdrage
  • Identificatie:
    2019;4:a1718
  • Auteur(s):
    Dr. Maarten J. Beinema a*, dr. Henk J. Adriaansen b, prof. dr. Hugo ten Cate c, dr. Laura M. Faber d, dr. Angelique T.M. van Holten-Verzantvoort e, dr. Melchior C. Nierman f, dr. R.W.L.M. Niessen g en em. prof. dr. J.R.B.J. Brouwers h

VKA-beleid in het DOAC-tijdperk: fenprocoumon ten opzichte van acenocoumarol

VKA policy in the DOAC era: phenprocoumon versus acenocoumarol

BACKGROUND and OBJECTIVE

Vitamin K antagonists (VKAs) are still used for the prevention of thromboembolic events. In Europe acenocoumarol and phenprocoumon are frequently prescribed. In the Netherlands acenocoumarol is the most prescribed VKA.

DESIGN and METHODS

This article describes the differences between these two drugs: acenocoumarol and phenprocoumon.

RESULTS and CONCLUSION

Phenprocoumon is characterized by an extremely long half-life (160 hours), which leads to a better time in therapeutic range. Phenprocoumon dosing however, is more difficult and requires more often vitamin K interventions. Due to pharmacogenetic differences between these two anticoagulants, phenprocoumon is probably less sensitive to drug-drug interactions.

21 nov 2019

Dosisescalatie van capecitabine na initiële verlaging bij heterozygote dragers van DPYD-variant

  • Rubriek:
    Referaat
  • Identificatie:
    2019;4:e1691
  • Auteur(s):
    Ithamar Brinkman

Dosisescalatie van capecitabine na initiële verlaging bij heterozygote dragers van DPYD-variant

08 nov 2019

Verhoogd risico op een methotrexaatintoxicatie op oudere leeftijd

  • Rubriek:
    Casuïstische mededeling
  • Identificatie:
    2019;4:a1714
  • Auteur(s):
    Laure J.M.J. Vorstenbosch a*, Marieke Kerskes b en Michiel W.H. van Beek c

Verhoogd risico op een methotrexaatintoxicatie op oudere leeftijd

Increased risk of methotrexate intoxication in the elderly

INTRODUCTION

Over two decades, low dose methotrexate (MTX) has been used as a therapy for rheumatoid arthritis and psoriasis [1,2]. The biggest risk of MTX therapy is the development of toxicity with associated side effects and ultimately mortality. Low dose methotrexate use in elderly patients more often leads to MTX intoxication with serious consequences. For atypical complaints in frail older people using methotrexate, the MTX intoxication should be in the differential diagnosis. In this article we describe a patient presenting with atypical complaints as a result of an MTX intoxication.

DESCRIPTION

A 76-year-old female presents with severe dyspnea, during rehabilitation therapy of a recently experienced stroke. She has heart failure NYHA class II and rheumatoid arthritis. She is treated with a low dose schedule of methotrexate, 10 mg per week combined with folic acid 5 mg three times per week and hydroxychloroquine (Plaquenil) 200 mg once daily.

Additional laboratory tests show abnormal values including increased liver values, impaired renal function and bone marrow suppression. Because of known MTX use in combination with the laboratory abnormalities found with unclear underlying cause, an MTX blood level is determined. This appears to be largely increased. Calcium folinate is started intravenously, despite improving blood results the patient does not improve and a palliative policy is followed.

DISCUSSION

For atypical complaints in frail older people using methotrexate, the MTX intoxication should be in the differential diagnosis. Measuring methotrexate levels is unusual in Dutch rheumatology, partly due to the short half-life of MTX. Literature study shows several cases in which inadequate intake of MTX – as well as adequate intake – leads to an MTX intoxication. Decreased kidney function leads to an increased risk of MTX intoxication. Therefore it is, especially in elderly patients with MTX therapy, advisable to frequently check renal function. Dose adjustment should be made in case of impaired renal function and measurement of MTX levels should be considered. Elderly presenting atypical complaints is a common sight. Doctors should ensure that MTX therapy is adequately followed and MTX intoxication must be in the differential diagnosis in elderly with atypical complaint presentation.

CONCLUSION

The risk of developing MTX intoxication in frail elderly is increased despite prescription MTX use. In this category of patients, this often leads to an atypical complaint presentation. For atypical complaints in frail older people using methotrexate, the MTX intoxication should be in the differential diagnosis. Especially with a reduced kidney function, the risk of an MTX-intoxication is higher. In addition, with MTX use the dose regime and actual intake must be extensively requested to prevent fatal consequences.

24 okt 2019

De ontwikkeling van budesonidetabletten met nulde-orde-afgifte voor de behandeling van ileo-colonische inflammatoire darmziekten en vergelijking met huidige, commerciële preparaten

  • Rubriek:
    Korte bijdrage
  • Identificatie:
    2019;4:a1715
  • Auteur(s):
    Bahez Gareb ab*, Gerard Dijkstra c, Jos G.W. Kosterink ad en Henderik W. Frijlink b

De ontwikkeling van budesonidetabletten met nulde-orde-afgifte voor de behandeling van ileo-colonische inflammatoire darmziekten en vergelijking met huidige, commerciële preparaten

Development of novel zero-order release budesonide tablets for the treatment of ileo-colonic inflammatory bowel disease and comparison with formulations currently used in clinical practice

BACKGROUND

In patients with inflammatory bowel disease, the terminal ileum and colon is the most affected region. Oral budesonide is an effective treatment but in vitro as well as clinical data suggest that the formulations currently used in clinical practice are suboptimal to treat the entire ileo-colonic region.

OBJECTIVE and DESIGN

The aim of this in vitro study was to develop ileo-colonic-targeted zero-order sustained-release tablets containing 3 mg or 9 mg budesonide (ColoPulse 3 mg and 9 mg, respectively).

METHODS

Tablets were tested in a 10 hour gastrointestinal simulation system for site-specific release, zero-order release kinetics (R2 ≥ 0.95), release rate, and completeness of release (≥ 80%). Release profiles of the novel formulations were compared with Entocort, Budenofalk, and Cortiment (budesonide MMX).

RESULTS

None of these formulations currently used in clinical practice targeted the entire ileo-colonic region. However, ColoPulse 3 mg and 9 mg were targeted to the ileum, released the entire dose with zero-order release kinetics in the ileo-colonic region, and complied with a 6-month accelerated stability study.

CONCLUSION

Therefore, ColoPulse 3 mg and 9 mg are novel, interesting formulations for the treatment of the entire ileo-colonic region in inflammatory bowel disease.

04 okt 2019

Het effect van een uitgebreide medicatieverificatietool op het aantal onbedoelde klinisch relevante medicatiediscrepanties bij opname van de psychiatrische patiënt

  • Rubriek:
    Korte bijdrage
  • Identificatie:
    2019;4:a1711
  • Auteur(s):
    V. Akrum a*, M. Duisenberg-van Essenberg a, N. Veth b en B. Maat a

Het effect van een uitgebreide medicatieverificatietool op het aantal onbedoelde klinisch relevante medicatiediscrepanties bij opname van de psychiatrische patiënt

The effect of a customized medication verification tool on the amount of unintended clinically relevant medication discrepancies at hospital admission of psychiatric patients

BACKGROUND

Unintended medication discrepancies (UMDs) at admission is common in hospitalized patients. Studies have shown that medication verification at admission resulted in fewer UMDs. Medication reconciliation studies in psychiatric patients are scarce. At the time of this study, medication verification in the medical psychiatric unit (MPU) of the Elisabeth-Tweesteden Hospital was done by the attending physician. After evaluating this process a customized verification tool was developed.

OBJECTIVE

The effect of using a customized medication verification tool by a pharmacy technician on the prevention of clinically relevant UMDs in psychiatric patients admitted to the MPU of the Elisabeth-Tweesteden Hospital.

DESIGN

A randomized prospective intervention study.

METHODS

Patients admitted to the MPU – who met the inclusion criteria – were randomized in group A, B or C. In group A medication was verified by the attending physician. In group B and C medication was verified by a pharmacy technician using a standardized or customized verification tool, respectively. UMDs were assessed within 24 hours of admission. A panel determined clinical relevancy of the UMDs using the National Coordinating Council for Medication Error Reporting and Prevention (NCCMERP) index. Categories E till I were considered clinically relevant.

RESULTS

The interim analysis showed 33 UMDs in group A (n = 31), 59 in group B (n = 44), and 88 in group C (n = 42). The amount of clinically relevant UMDs per patient in group A, B, and C was 0.32, 0.27, and 0.57, respectively. The majority of the UMDs were omissions and included mostly non-psychiatric medication.

CONCLUSION

The interim analysis shows relatively more clinically relevant UMDs per patient when medication was verified by a pharmacy technician using a customized verification tool. It is possible that medication verification with a customized verification tool by a pharmacy technician results in the prevention of clinically relevant unintended medication discrepancies.

25 sep 2019

Variabiliteit in farmacokinetiek van intraveneuze paracetamol bij gezonde ouderen

  • Rubriek:
    Oorspronkelijk artikel
  • Identificatie:
    2019;4:a1713
  • Auteur(s):
    P. Mian a*, M.J. van Esdonk b, B.C.M. de Winter c, I. Spriet d, D. Tibboel e, M. Petrovic f, K. Allegaert gh en B.C.P. Koch h

Variabiliteit in farmacokinetiek van intraveneuze paracetamol bij gezonde ouderen

Variability in pharmacokinetics of intravenous paracetamol in healthy older people

BACKGROUND and OBJECTIVE

Paracetamol is the most used analgesic in older people. The physiological changes occurring with ageing influence the pharmacokinetics of paracetamol and its variability. A population pharmacokinetic analysis to describe the pharmacokinetics of intravenous paracetamol in fit older people was performed. Thereafter, simulations were conducted to illustrate target attainment and variability of paracetamol exposure following current dosing regimens (1000 mg q6h, q8h) using steady-state concentration (Css-mean) of 10 mg/L as target for effective analgesia.

DESIGN and METHODS

A population pharmacokinetic-analysis, using NONMEM 7.2, was performed based on 601 concentrations of paracetamol from 30 fit older people (median age = 77.3 years [61.8- 88.5], body weight = 79 kg [60-107]). All had received an intravenous paracetamol dose of 1000 mg – over 15 min – after elective knee surgery.

RESULTS

A two-compartment pharmacokinetic-model best described the data. Volume of distribution of paracetamol increased exponentially with body weight. Clearance was not influenced by any covariate. Simulations of the standardized dosing regimens resulted in a Css-mean of 9.2 mg/L (q6h) and 7.2 mg/L (q8h). Variability in paracetamol pharmacokinetics resulted in a Css-mean above 5.4 (q6h) and 4.1 mg/L (q8h) in 90%, and above 15.5 (q6h) and 11.7 mg/L (q8h) in 10% of the population.

CONCLUSION

The target concentration was achieved in the average patient with 1000 mg q6h, while q8h resulted in underdosing for the majority of the population. Due to large unexplained inter-individual variability in paracetamol pharmacokinetics a relevant proportion of the fit older people remained either under- or overexposed.

16 sep 2019

Associatie van single-nucleotide polymorphisms in UGT1, NR1I2, ABCC2, ABCC5 en ABCG1 met irinotecangeïnduceerde toxiciteit in colorectaalkanker

  • Rubriek:
    Korte bijdrage
  • Identificatie:
    2019;4:a1702
  • Auteur(s):
    Sander Ketzer *, Henk-Jan Guchelaar en Jesse Swen

Associatie van single-nucleotide polymorphisms in UGT1, NR1I2, ABCC2, ABCC5 en ABCG1 met irinotecangeïnduceerde toxiciteit in colorectaalkanker

Association of single-nucleotide polymorphisms in UGT1, NR1I2, ABCC2, ABCC5 and ABCG1 with irinotecan-induced toxicity in colorectal cancer

BACKGROUND

Irinotecan is used in the palliative treatment of metastatic colorectal cancer. Its metabolism is complex with many different transporters and enzymes involved. For UGT1A1*28 (rs8175347), an association with irinotecan-induced toxicity has been established. Recent studies suggested that other single-nucleotide polymorphisms (SNPs) within genes encoding irinotecan-related enzymes and transporters can lead to reduced or increased irinotecan-induced toxicity, mainly diarrhoea and neutropenia.

OBJECTIVE

In this study we aim to replicate associations between SNPs related to UGT1 rs11563250; NR1I2 rs10934498, rs2472677, rs3814055 and rs1523127; ABCC5 rs10937158, rs3749438, rs562 and rs2292997; ABCG1 rs225440 and ABCC2 rs717620 and grade 3 to 4 diarrhoea and febrile neutropenia in a population of 221 mCRC patients treated with irinotecan. The well-known UGT1A1*28 variant is also evaluated.

DESIGN

Retrospective clinical association study.

METHODS

DNA samples used for this study were obtained from patients participating in the CAIRO study (NCT00312000). The DNA samples were genotyped for twelve SNPs, selected on the basis of the results of previously published studies. For the main analysis, associations between SNPs and toxicity data were tested with logistic regression.

RESULTS

ABCC2 rs717620T is significantly associated with grade > 3 febrile neutropenia (OR = 2.72; P = 0.025). UGT1A1*28 shows significant associations with an increased risk on grade 3 to 4 diarrhoea (OR = 1.76, P = 0.035) and grade 3 to 4 febrile neutropenia (OR = 3; P = 0.01).

CONCLUSION

The outcomes of previous studies could not be replicated, except for UGT1A1*28. Moreover, we found an association with the opposite direction of effect between ABCC2 rs717620T and severe neutropenia. Based on the outcomes of this study genotyping for the tested variants – with exception of UGT1A1*28 – cannot be recommended.

06 sep 2019

Therapeutisch gedoseerde laag-molecuulgewicht heparines bij patiënten met obesitas: doseren op basis van lichaamsgewicht zonder afkapgrens

  • Rubriek:
    Oorspronkelijk artikel
  • Identificatie:
    2019;4:a1708
  • Auteur(s):
    G.T. de Vries a*, A.L. van Ojik b, M. Hoogendoorn c en E.N. van Roon de

Therapeutisch gedoseerde laag-molecuulgewicht heparines bij patiënten met obesitas: doseren op basis van lichaamsgewicht zonder afkapgrens

Therapeutic use of low molecular weight heparins in obese patients: dosing based on body weight without cut-off limit

BACKGROUND

The correct dose of therapeutic low molecular weight heparins (LMWHs) in patients with a body mass index ≥ 30 kg/m2 is uncertain. Literature and guidelines are not clear and consistent about the correct dose.

DESIGN and METHODS

In this review, an overview of the literature on therapeutic use of LMWHs in this population is provided. Sixteen pharmacokinetic and pharmacodynamic or clinical studies were included.

RESULTS

Based on these results, obese patients should receive therapeutic doses of LMWHs, based on their total body weight without a dose cap as recommended in the Summary of Product Characteristics. In patients with morbid obesity, anti-Xa level monitoring and subsequently an adjusted dosage on the base of supratherapeutic anti-Xa levels is recommended.