Elisabeth J Ruijgrok

Publications (6)21.58 Total impact

• Article: A review on the clinical use of inhaled amphotericin B.

  Laura Kuiper, Elisabeth J Ruijgrok
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  ABSTRACT: Despite the systemic toxicity of amphotericin B (AMB), it still has a place in treatment or prophylactic regimes of fungal infections. A strategy for minimizing the potential of systemic side effects is to bring it in direct contact with the body site most likely to be infected, such as the administration of AMB as an aerosol. Nebulized amphotericin has been used in humans since 1959. However, due to a lack of sufficient data regarding efficacy, its use is still not established. Little is known about the optimal dose, frequency, duration of administration, and the pharmacokinetics of inhaled AMB in humans. In this review, published data regarding inhaled AMB are summarized, including available descriptions regarding preparation, dose, efficacy, and toxicity, and its place in therapy is discussed. The results from the studies that were reviewed in this article indicate that inhaled AMB may have a place in the prophylactic regimens of patients with prolonged neutropenia and in lung transplant recipients. Furthermore, nebulized (liposomal) AMB may have a place in the treatment of allergic bronchopulmonary aspergillosis (ABPA) in patients with corticosteroid-dependent ABPA.
  Journal of Aerosol Medicine and Pulmonary Drug Delivery 04/2009; 22(3):213-27. · 2.20 Impact Factor
• Article: Sterically Stabilized Liposomes Containing Gentamicin: Limitations to Gentamicin Encapsulation

  Elisabeth J. Ruijgrok, Arnold G. Vulto, Els W.M van Etten
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  ABSTRACT: Abstract As sterically stabilized liposomes (SSL) containing the aminoglycoside gentamicin prepared by the method of passive loading are characterized by a low drug to lipid ratio, we attempted to prepare gentamicin containing SSL with a more efficient encapsulation. Passive loading of a dried lipid film (PEG-DSPE:PHEPC: cholesterol = 0.15:1.85:1.0) with a solution containing 125 mg gentamicin per 250 μmole lipid yielded liposomes with an encapsulation efficiency of 4.0 ± 0.4% and a gentamicin loading of 28.0 ± 0.7 μg gentamicin/μmole lipid. Encapsulation efficiency was calculated as the percentage of gentamicin incorporated into liposomes relative to the initial total amount of gentamicin in solution and gentamicin loading was calculated as the amount of gentamicin incorporated in liposomes relative to the content of total lipid. Active loading of gentamicin into preformed liposomes which exhibit a transmembrane pH gradient resulted in a lower encapsulation efficiency and gentamicin loading (0.4 ± 0.1% and 4.3 ± 1.2 μg/μmole, respectively). Addition of calcium ions to the hydration buffer did not alter the encapsulation efficiency nor the gentamicin loading in both loading strategies. In conclusion, it seems that the encapsulation efficiency for gentamicin in SSL with the lipid composition PEG-DSPE, PHEPC and cholesterol (in a molar ratio 0.15:1.85: 1.0) is limited to 4%, or 28 μg gentamicin per μmole lipid. The preparation method to achieve this encapsulation is the passive loading of liposomes with gentamicin.
  09/2008; 9(2):291-300.
• Source

  Available from: Jeanette K Doorduijn

  Article: Aerosolized liposomal amphotericin B for the prevention of invasive pulmonary aspergillosis during prolonged neutropenia: a randomized, placebo-controlled trial.

  Bart J Rijnders, Jan J Cornelissen, Lennert Slobbe, Martin J Becker, Jeanette K Doorduijn, Wim C J Hop, Elisabeth J Ruijgrok, Bob Löwenberg, Arnold Vulto, Pieternella J Lugtenburg, Siem de Marie
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  ABSTRACT: Invasive pulmonary aspergillosis (IPA) is a significant problem in patients with chemotherapy-induced prolonged neutropenia. Because pulmonary deposition of conidia is the first step in developing IPA, we hypothesized that inhalation of liposomal amphotericin B would prevent IPA. We performed a randomized, placebo-controlled trial of patients with hematologic disease with expected neutropenia for >or=10 days. Patients were randomized to receive liposomal amphotericin B or placebo inhalation twice a week, using an adaptive aerosol delivery system, until neutrophil counts increased to >300 cells/mm3. In subsequent neutropenic episodes, the assigned treatment was restarted. The primary end point was the occurrence of IPA according to European Organization for Research and the Treatment of Cancer-Mycoses Study Group definitions. Kaplan-Meier curves were compared with log-rank tests for intent-to-treat and on-treatment populations. A total of 271 patients were studied during 407 neutropenic episodes. According to the intent-to-treat analysis, 18 of 132 patients in the placebo group developed IPA versus 6 of 139 patients in the liposomal amphotericin B group (odds ratio, 0.26; 95% confidence interval, 0.09-0.72; P=.005). According to the on-treatment analysis, 13 of 97 patients receiving placebo versus 2 of 91 receiving liposomal amphotericin B developed IPA (odds ratio, 0.14; 95% confidence interval, 0.02-0.66; P=.007). Some adverse effects, but none serious, in the liposomal amphotericin B group were reported, most frequently coughing (16 patients vs. 1 patient; P=.002). In high-risk patients, prophylactic inhalation of liposomal amphotericin B significantly reduced the incidence of IPA.
  Clinical Infectious Diseases 05/2008; 46(9):1401-8. · 9.15 Impact Factor
• Article: Nebulized amphotericin B combined with intravenous amphotericin B in rats with severe invasive pulmonary aspergillosis.

  Elisabeth J Ruijgrok, Marcel H A M Fens, Irma A J M Bakker-Woudenberg, Els W M van Etten, Arnold G Vulto
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  ABSTRACT: Nebulized amphotericin B (AMB) combined with intravenous AMB was studied in persistently leukopenic rats with invasive pulmonary aspergillosis. Pulmonary concentrations of AMB after aerosol treatment were substantially higher than after intravenous liposomal AMB. Nebulized liposomal AMB in addition to intravenous AMB resulted in significantly prolonged survival compared to controls.
  Antimicrobial Agents and Chemotherapy 06/2006; 50(5):1852-4. · 4.84 Impact Factor
• Article: Nebulization of four commercially available amphotericin B formulations in persistently granulocytopenic rats with invasive pulmonary aspergillosis: evidence for long-term biological activity.

  Elisabeth J Ruijgrok, Marcel H A Fens, Irma A J M Bakker-Woudenberg, Els W M van Etten, Arnold G Vulto
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  ABSTRACT: The nebulization of amphotericin B desoxycholate (AMB-DOC), liposomal amphotericin B (L-AMB), amphotericin B lipid complex (ABLC) and amphotericin B colloidal dispersion (ABCD) has been investigated. Particle sizes of generated aerosol droplets were measured. Pulmonary amphotericin B deposition and amphotericin B concentration in blood directly after nebulization and at six weeks after nebulization was measured in healthy rats. The efficacy of nebulized amphotericin B formulations was evaluated in persistently granulocytopenic rats with invasive pulmonary aspergillosis. Treatment was given either after or before fungal inoculation. The endpoint was survival of animals. Aerosol particle sizes, expressed as the values for the mass median diameter were 1.38, 2.43, 0.90 and 2.29 microm for AMB-DOC, L-AMB, ABLC and ABCD, respectively. Amphotericin B concentrations in the lungs directly after nebulization exceeded the minimum inhibitory concentration of Aspergillus fumigatus and amphotericin B was still detected in lungs of rats at six weeks after nebulization. Treatment, started at 16 h after fungal inoculation, resulted in a significantly prolonged survival as compared with sham-treated rats for all four formulations. Prophylactic treatment at one week before fungal inoculation resulted in a significantly prolonged survival for all four formulations. Aerosol treatment given at two weeks before inoculation was effective only for AMB-DOC and L-AMB, whereas treatment given at six weeks resulted in a significantly prolonged survival for L-AMB only. All commercially available amphotericin B preparations could be nebulized efficiently and may be of value in the prophylactic treatment of invasive pulmonary aspergillosis.
  Journal of Pharmacy and Pharmacology 11/2005; 57(10):1289-95. · 2.17 Impact Factor
• Source

  Available from: Jacques Meis

  Article: Pharmacological agents in development for invasive aspergillosis.

  Elisabeth J Ruijgrok, Jaques F G M Meis
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  ABSTRACT: The urgent medical need for new potent antifungal agents in the management of invasive aspergillosis (IA) has resulted in the development of several compounds which may be of value in the future for the treatment or prophylaxis of IA. In the past years, several novel types of drugs have been discovered and developed, some of which are already in late-stage clinical trials and ready to enter the market. This paper discusses the antifungal agents, classified by their mode of action, that are currently available and the agents which are still in development for treatment or prevention of IA.
  Expert Opinion on Emerging Drugs 06/2002; 7(1):33-45. · 3.21 Impact Factor