Farmaceutisch onderzoek

834 artikelen

18 apr 2019

Het optreden van neutropenie na docetaxelblootstelling bij patiënten met gemetastaseerde castratieresistente prostaatkanker

  • Rubriek:
    Referaat
  • Identificatie:
    2019;4:e1683
  • Auteur(s):
    András Vermes

Het optreden van neutropenie na docetaxelblootstelling bij patiënten met gemetastaseerde castratieresistente prostaatkanker

10 apr 2019

Farmacokinetiek en tolerantie van eenmaal daagse verneveling van de dubbele dosis tobramycine bij cystische fibrose: vergelijking tussen PARI-LC Plus- en AKITA-vernevelaar

  • Rubriek:
    Korte bijdrage
  • Identificatie:
    2019;4:a1694
  • Auteur(s):
    A.J. van Velzen a*, A.C. Bos bc, D.J. Touw d, H.A.W.M. Tiddens bc, H.G.M. Heijerman e en H.M. Janssens b

Farmacokinetiek en tolerantie van eenmaal daagse verneveling van de dubbele dosis tobramycine bij cystische fibrose: vergelijking tussen PARI-LC Plus- en AKITA-vernevelaar

Pharmacokinetics and tolerability of once daily double dose tobramycin inhalation in cystic fibrosis using controlled and conventional nebulization: comparison between PARI-LC Plus and AKITA nebulizer

OBJECTIVE

Better treatment outcomes in cystic fibrosis (CF) may be expected by changing standard twice daily tobramycin inhalation with the conventional PARI-LC Plus nebulizer to once daily inhalation of the double dose with the controlled-inhalation AKITA nebulizer. We aimed to determine pharmacokinetics (PK) and safety of once daily inhalation of the double recommended tobramycin dose with the AKITA in patients with CF. Systemic absorption can be used as surrogate for safety.

DESIGN and METHODS

In a randomized open-label crossover pilot study, PK of inhaled tobramycin in 10 adult CF patients was assessed following inhalation of the double recommended dose with the AKITA (300 mg fill dose) and PARI-LC Plus (600 mg fill dose). Blood samples were drawn until 24 hours after inhalation.

RESULTS

No significant differences were found in the maximum and trough serum levels, time to maximum level and area under the curve (0-24 hours). Both maximum and trough levels were well below their toxic limits for both nebulizers and for all patients. Both inhalations were well tolerated and no serious adverse events occurred. Nebulization time was 33% shorter with AKITA.

CONCLUSION

Once daily inhalation of the double tobramycin dose with the controlled-inhalation AKITA nebulizer resulted in safe serum levels, with comparable systemic exposure to once daily PARI-LC Plus inhalation and higher peak levels compared to the standard twice daily dosing regimen. Inhalation with both nebulizers was well tolerated. Nebulization time was significantly shortened, less side effects were reported and a higher degree of satisfaction was attained with the AKITA nebulizer.

08 apr 2019

Speeksel als potentiële alternatieve matrix voor het bepalen van levofloxacine bij tuberculosepatiënten

  • Rubriek:
    Referaat
  • Identificatie:
    2019;4:e1682
  • Auteur(s):
    András Vermes

Speeksel als potentiële alternatieve matrix voor het bepalen van levofloxacine bij tuberculosepatiënten

04 apr 2019

Evaluatie van een nieuwe Nederlandse vancomycinedoseerrichtlijn en populatiefarmacokinetiek van vancomycine bij preterme en a terme neonaten

  • Rubriek:
    Korte bijdrage
  • Identificatie:
    2019;4:a1695
  • Auteur(s):
    L. Koedood ab*, T.R. de Haan c, C.J. Hodiamont d, I.M.M. van Haelst a en R.A.A. Mathôt b

Evaluatie van een nieuwe Nederlandse vancomycinedoseerrichtlijn en populatiefarmacokinetiek van vancomycine bij preterme en a terme neonaten

Evaluation of a new Dutch guideline for vancomycin dosing and population pharmacokinetics of vancomycin for preterm and term neonates

OBJECTIVE

In May 2015 the Dutch pediatric formulary (Kinderformularium) introduced a new guideline for dosing of vancomycin in neonates. The primary aim of this study was to validate this guideline by assessing the percentage of therapeutic initial trough serum concentrations in a cohort of (pre)term neonates. The secondary aim of this study was to describe the population pharmacokinetics (PPK) of vancomycin in (pre)term neonates.

METHODS

In this prospective study, (pre)term neonates were included when admitted to the Neonatology department of the Academic Medical Center, Amsterdam from May 2015 to June 2017. Vancomycin dosing was performed according to the new guideline. Serum concentrations were measured prior to the administration of the fifth dose. Trough levels in the range of 10 to 15 mg/L were considered therapeutic. PPK parameters were estimated by nonlinear mixed-effects modeling.

RESULTS

Forty patients were included for the primary aim and 42 patients for the secondary aim of this study. The main category of patients were premature neonates with a postnatal age of 1 to 4 weeks (n = 27, 68%). In this group 15 patients (56%) had a subtherapeutic vancomycin serum level, while therapeutic and supratherapeutic levels were found in 7 (26%) and 5 (19%) of the patients, respectively. The PPK were best described by an allometric, one-compartment model. Inter-patient variability in clearance could be explained by variation in renal function and postmenstrual age.

CONCLUSION

The new dosing guideline does not produce therapeutic vancomycin concentrations in the majority of premature neonates from 1 to 4 weeks old. Further research is needed to optimize dosing of vancomycin in neonates.

28 mrt 2019

Specifiekere signalen nodig voor ondersteuning apothekers bij medicatiebeoordeling

  • Rubriek:
    Referaat
  • Identificatie:
    2019;4:e1681
  • Auteur(s):
    Sander Borgsteede

Specifiekere signalen nodig voor ondersteuning apothekers bij medicatiebeoordeling

21 mrt 2019

Relevantere signalen mogelijk door prospectief onderzoek naar QTc-verlenging

  • Rubriek:
    Referaat
  • Identificatie:
    2019;4:e1680
  • Auteur(s):
    Sander Borgsteede

Relevantere signalen mogelijk door prospectief onderzoek naar QTc-verlenging

15 mrt 2019

Redenen van patiënten om geen laxans te gebruiken bij opioïden

  • Rubriek:
    Referaat
  • Identificatie:
    2019;4:e1678
  • Auteur(s):
    Marcel Kooij

Redenen van patiënten om geen laxans te gebruiken bij opioïden

07 mrt 2019

Therapeutic drug monitoring van adalimumab bij patiënten met inflammatoire darmziekten

  • Rubriek:
    Korte bijdrage
  • Identificatie:
    2019;4:a1692
  • Auteur(s):
    W. van ’t Geloof a*, P.J. Boekema b, L.P.L. Gilissen c, M.A.C. Broeren d en L.J.J. Derijks a

Therapeutic drug monitoring van adalimumab bij patiënten met inflammatoire darmziekten

Therapeutic drug monitoring of adalimumab in inflammatory bowel disease patients

OBJECTIVE

Adalimumab (ADA) trough levels correlate with clinical remission. Despite suggestions that therapeutic drug monitoring of ADA can optimize treatment in this population, it is not yet implemented in clinical practice. This study was conducted to provide more insight in ADA trough levels and antibodies to adalimumab (ATA) in an inflammatory bowel disease (IBD) population already treated with adalimumab.

DESIGN

We carried out a prospective cohort study in IBD outpatients already treated with adalimumab.

METHODS

Patient demographics were collected from the electronic hospital information system. Blood was drawn for determination of ADA trough levels and ATAs. Disease activity indices for Crohn’s disease and ulcerative colitis and quality of life scores were obtained by a questionnaire.

RESULTS

A total of 92 patients was included. ADA levels varied from < 0.1 to 20.2 mg/L. Mean ADA level was 7.7 mg/L (SD = 4.5), 4 patients developed ATAs. ADA levels ≤ 5 mg/L were demonstrated in 27 patients (29%). The ADA level was not significantly associated with remission (P = 0.391). Quality of life score correlated with ADA level (P = 0.031).

CONCLUSION

Therapeutic drug monitoring in inflammatory bowel disease outpatients revealed large interindividual differences in adalimumab trough levels. These levels were subtherapeutic in nearly a third of patients. We think, despite no significant correlation was found between adalimumab trough level and disease activity, therapeutic drug monitoring has the potential to individualize treatment in inflammatory bowel disease patients using adalimumab.

28 feb 2019

Nierfunctie en ernstige bloedingen bij patiënten behandeld met cumarines

  • Rubriek:
    Oorspronkelijk artikel
  • Identificatie:
    2019;4:a1691
  • Auteur(s):
    Eline Houben a*, Elisabeth Smits a, Jetty A. Overbeek ab, dr. Fernie J.A. Penning-van Beest a, dr. Ron M.C. Herings a, dr. Myrthe P.P. van Herk-Sukel a, dr. Martina Teichert cde en prof. dr. Peter A.G.M. de Smet cd

Nierfunctie en ernstige bloedingen bij patiënten behandeld met cumarines

No evidence for an association between renal function and serious bleeding events in patients treated with coumarins

BACKGROUND

Although anticoagulation therapy is closely monitored in the Netherlands, coumarin-induced serious bleeding events are still observed. Current literature suggests that renal impairment may contribute to this.

OBJECTIVE

To explore the association between renal function and bleeding events during coumarin treatment.

DESIGN

A nested case-control study was conducted using data from the PHARMO Database Network.

METHODS

Patients hospitalised for a bleeding event during coumarin treatment were selected as cases and matched on sex, birth year, and geographic region with a maximum of two controls using coumarins without hospitalisation for bleeding. All values of estimated glomerular filtration rates (eGFRs) in the year before index date (case hospitalisation date) were selected and compared between cases and controls using logistic regression analyses.

RESULTS

In total, 2224 cases were matched to 4398 controls (61% male; mean age ± SD = 75 ± 11 and 78 ± 11 years for cases and controls, respectively). Availability of eGFR values was higher among cases compared with controls (mean eGFR values ± SD = 4.5 ± 7.1 versus 3.2 ± 5.5), reflected in the significantly shorter time since last eGFR value (at index date, mean ± SD = 2.7 ± 3.0 versus 3.8 ± 3.1 months; odds ratio [OR] = 0.91, 95%CI = 0.89-0.92). No statistically significant difference was found for the mean eGFR value in the year before index date (mean ± SD 65.7 ± 22.8 versus 64.6 ± 20.9 mL/min/1.73 m; OR per 10 units = 0.99, 95%CI = 0.96-1.02).

CONCLUSION

No association between renal function and serious bleeding events during coumarin treatment was observed.

18 feb 2019

De openbaar apotheker op huisbezoek na ontslag uit het ziekenhuis

  • Rubriek:
    Referaat
  • Identificatie:
    2019;4:e1677
  • Auteur(s):
    Marcel Kooij

De openbaar apotheker op huisbezoek na ontslag uit het ziekenhuis

06 feb 2019

Therapeutic drug monitoring van adalimumab bij reumatologische patiënten

  • Rubriek:
    Korte bijdrage
  • Identificatie:
    2019;4:a1690
  • Auteur(s):
    A.H. Kylstra a*, S. Benoy-de Keuster b, R.A.M. Traksel b, M.A.C. Broeren c en L.J.J. Derijks a

Therapeutic drug monitoring van adalimumab bij reumatologische patiënten

Therapeutic drug monitoring of adalimumab in rheumatic patients

OBJECTIVE and DESIGN

Adalimumab (ADA) is effective in the treatment of rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Despite suggestions that therapeutic drug monitoring (TDM) of ADA can optimize treatment of this population, it is not routinely implemented in clinical practice. We therefore carried out a prospective observational cohort study by measuring ADA levels in a population of patients with rheumatic diseases and related those levels to disease activity.

METHODS

Patient demographics were collected from the electronic hospital information system. Blood drawn before the regular outpatient visit was used for determination of ADA trough levels and antibodies against ADA (ATA). Objectified disease activity measurements were obtained at the appointment: DAS28 for RA, ASDAS for AS, and clinical assessment for SpA.

RESULTS

A total of 174 patients was included. ADA levels varied from less than 0.1 to 22.0 mg/L. The mean ADA level was 6.8 mg/L (standard deviation = 4.2). 5 patients (2,9%) developed ATA. The ADA level was significantly associated with remission (P = 0.002). The mean ADA level was 7.6 mg/L in patients in remission and 5.1 mg/L in patients with active disease. Use of immunosuppressants, frequency of administration, and body mass index were identified as significant covariates.

CONCLUSION

TDM of ADA demonstrated large interindividual differences in ADA levels. ADA trough levels were significantly associated with disease activity. TDM has the potential to individualize treatment and further research needs to show if it increases cost-effectiveness of this expensive therapy.

31 jan 2019

Een praktische gids voor probiotica ter preventie van antibiotica-gerelateerde diarree in Nederland

  • Rubriek:
    Oorspronkelijk artikel
  • Identificatie:
    2019;4:a1689
  • Auteur(s):
    Valeria Agamennone a, Cyrille A.M. Krul a, Ger Rijkers b en Remco Kort acd*

Een praktische gids voor probiotica ter preventie van antibiotica-gerelateerde diarree in Nederland

A practical guide for probiotics applied to the case of antibiotic-associated diarrhea in The Netherlands

BACKGROUND

Antibiotic-associated diarrhea (AAD) is a side-effect frequently associated with the use of broad spectrum antibiotics. Although a number of clinical studies show that co-administration of specific probiotics reduces the risk for AAD, there is still unclarity among healthcare professionals on the recommendation of probiotic products.

OBJECTIVE

This paper aims to provide a practical guide to inform healthcare professionals, patients and consumers about the exact product characteristics of available probiotics with a proven efficacy to prevent AAD.

DESIGN and METHODS

The workflow in this paper includes three consecutive steps: a systematic review of relevant clinical studies for effective probiotics by a meta-analysis, compilation of a list of available probiotic products, and recommendation of probiotic products that match effective formulations. Our systematic review on the efficacy of probiotics for the prevention of AAD included only studies with randomized, double blind placebo-controlled trials, a clear definition of antibiotic associated diarrhea, and a probiotic administration regime for at least the duration of the antibiotic therapy.

RESULTS

Using our inclusion criteria, we selected 32 out of 128 identified trials and pooled the results of these studies for each specific dairy product and food supplement. The results indicate a total of seven single or multiple-strain formulations favoring the probiotic treatment group, with the strain Lactobacillus rhamnosus GG being the most effective (relative risk ratio of probiotic versus placebo 0.30 with 95% CI 0.16 - 0.5). We selected products for recommendation from a compiled list of all probiotic dairy products and food supplements available in The Netherlands and categorized them into groups of products showing effects against the incidence of AAD in at least one, two, or three independent clinical studies. We excluded all products which did not unambiguously declare on the label the specific probiotic strain(s) and the number of colony forming units.

CONCLUSION

Here, we present a practical guide that informs healthcare professionals and patients on the availability of probiotic products with a proven efficacy for the prevention of AAD.

25 jan 2019

Dankbetuiging 2018

  • Rubriek:
    Redactioneel
  • Identificatie:
    2019;4:e1679
  • Auteur(s):
    Redactiebureau NPFO

Dankbetuiging 2018

16 jan 2019

Impact van CYP3A4*22 op pazopanibfarmacokinetiek bij patiënten met kanker

  • Rubriek:
    Referaat
  • Identificatie:
    2019;4:e1676
  • Auteur(s):
    André Wieringa

Impact van CYP3A4*22 op pazopanibfarmacokinetiek bij patiënten met kanker

11 jan 2019

Hoe om te gaan met genotypeergegevens van dragers van twee verschillende DPD-genvariaties

  • Rubriek:
    Referaat
  • Identificatie:
    2019;4:e1675
  • Auteur(s):
    Bob Wilffert

Hoe om te gaan met genotypeergegevens van dragers van twee verschillende DPD-genvariaties

03 jan 2019

Prisma Symposium, 15 mei 2018

  • Rubriek:
    Congresabstracts
  • Identificatie:
    2019;4:a1688
  • Auteur(s):
    Redactiebureau NPFO - verscheidene auteurs

Prisma Symposium, 15 mei 2018