المؤلفون: van de Stadt, Eveline Annette, Yaqub, Maqsood, Schuit, Robert C, Bartelink, Imke H, Leeuwerik, Anke F, Schwarte, Lothar A, de Langen, Adrianus J, Hendrikse, Harry, Bahce, Idris

المصدر: van de Stadt , E A , Yaqub , M , Schuit , R C , Bartelink , I H , Leeuwerik , A F , Schwarte , L A , de Langen , A J , Hendrikse , H & Bahce , I 2022 , ' Relationship between Biodistribution and Tracer Kinetics of 11C-Erlotinib, 18F-Afatinib and 11C-Osimertinib and Image Quality Evaluation Using Pharmacokinetic/Pharmacodynamic Analysis in Advanced Stage Non-Small Cell Lung Cancer Patients ' , Diagnostics (Basel, Switzerland) , vol. 12 , no. 4 , 883 . https://doi.org/10.3390/diagnostics12040883Test , https://doi.org/10.3390/diagnostics12040883Test

الوصف: BACKGROUND: Patients with non-small cell lung cancer (NSCLC) driven by activating epidermal growth factor receptor (EGFR) mutations are best treated with therapies targeting EGFR, i.e., tyrosine kinase inhibitors (TKI). Radiolabeled EGFR-TKI and PET have been investigated to study EGFR-TKI kinetics and its potential role as biomarker of response in NSCLC patients with EGFR mutations (EGFRm). In this study we aimed to compare the biodistribution and kinetics of three different EGFR-TKI, i.e., 11C-erlotinib, 18F-afatinib and 11C-osimertinib. METHODS: Data of three prospective studies and 1 ongoing study were re-analysed; data from thirteen patients (EGFRm) were included for 11C-erlotinib, seven patients for 18F-afatinib (EGFRm and EGFR wild type) and four patients for 11C-osimertinib (EGFRm). From dynamic and static scans, SUV and tumor-to-blood (TBR) values were derived for tumor, lung, spleen, liver, vertebra and, if possible, brain tissue. AUC values were calculated using dynamic time-activity-curves. Parent fraction, plasma-to-blood ratio and SUV values were derived from arterial blood data. Tumor-to-lung contrast was calculated, as well as (background) noise to assess image quality. RESULTS: 11C-osimertinib showed the highest SUV and TBR (AUC) values in nearly all tissues. Spleen uptake was notably high for 11C-osimertinib and to a lesser extent for 18F-afatinib. For EGFRm, 11C-erlotinib and 18F-afatinib demonstrated the highest tumor-to-lung contrast, compared to an inverse contrast observed for 11C-osimertinib. Tumor-to-lung contrast and spleen uptake of the three TKI ranked accordingly to the expected lysosomal sequestration. CONCLUSION: Comparison of biodistribution and tracer kinetics showed that 11C-erlotinib and 18F-afatinib demonstrated the highest tumor-to-background contrast in EGFRm positive tumors. Image quality, based on contrast and noise analysis, was superior for 11C-erlotinib and 18F-afatinib (EGFRm) scans compared to 11C-osimertinib and 18F-afatinib (EGFR wild type) scans.

العلاقة: https://research.vumc.nl/en/publications/59d5e233-c17f-4304-9840-4d7df51e627dTest

الإتاحة: https://doi.org/10.3390/diagnostics12040883Test
https://research.vumc.nl/en/publications/59d5e233-c17f-4304-9840-4d7df51e627dTest
http://www.scopus.com/inward/record.url?scp=85128580775&partnerID=8YFLogxKTest

المؤلفون: Bartelink, I. H., van de Stadt, E. A., Leeuwerik, A. F., Thijssen, V. L. J. L., Hupsel, J. R., I, van den Nieuwendijk, J. F., Bahce, I, Yaqub, M., Hendrikse, N. H.

المصدر: Bartelink , I H , van de Stadt , E A , Leeuwerik , A F , Thijssen , V L J L , Hupsel , J R I , van den Nieuwendijk , J F , Bahce , I , Yaqub , M & Hendrikse , N H 2022 , ' Physiologically Based Pharmacokinetic (PBPK) Modeling to Predict PET Image Quality of Three Generations EGFR TKI in Advanced-Stage NSCLC Patients ' , Pharmaceuticals , vol. 15 , no. 7 , 796 . https://doi.org/10.3390/ph15070796Test , https://doi.org/10.3390/ph15070796Test

الوصف: Introduction: Epidermal growth factor receptor (EGFR) mutated NSCLC is best treated using an EGFR tyrosine kinase inhibitor (TKI). The presence and accessibility of EGFR overexpression and mutation in NSCLC can be determined using radiolabeled EGFR TKI PET/CT. However, recent research has shown a significant difference between image qualities (i.e., tumor-to-lung contrast) in three generation EGFR TKIs: 11 C-erlotinib, 18 F-afatinib and 11 C-osimertinib. In this research we aim to develop a physiological pharmacokinetic (PBPK)-model to predict tumor-to-lung contrast and as a secondary outcome the uptake of healthy tissue of the three tracers. Methods: Relevant physicochemical and drug specific properties (e.g., pKa, lipophilicity, target binding) for each TKI were collected and applied in established base PBPK models. Key hallmarks of NSCLC include: immune tumor deprivation, unaltered tumor perfusion and an acidic tumor environment. Model accuracy was demonstrated by calculating the prediction error (PE) between predicted tissue-to-blood ratios (TBR) and measured PET-image-derived TBR. Sensitivity analysis was performed by excluding each key component and comparing the PE with the final mechanistical PBPK model predictions. Results: The developed PBPK models were able to predict tumor-to-lung contrast for all EGFR-TKIs within threefold of observed PET image ratios (PE tumor-to-lung ratio of −90%, +44% and −6.3% for erlotinib, afatinib and osimertinib, respectively). Furthermore, the models depicted agreeable whole-body distribution, showing high tissue distribution for osimertinib and afatinib and low tissue distribution at high blood concentrations for erlotinib (mean PE, of −10.5%, range −158%–+190%, for all tissues). Conclusion: The developed PBPK models adequately predicted the image quality of afatinib and osimertinib and erlotinib. Some deviations in predicted whole-body TBR lead to new hypotheses, such as increased affinity for mutated EGFR and active influx transport (erlotinib into excreting tissues) or ...

العلاقة: https://research.vumc.nl/en/publications/886f4fc7-d3f4-4a12-be79-923bb03d7335Test

الإتاحة: https://doi.org/10.3390/ph15070796Test
https://research.vumc.nl/en/publications/886f4fc7-d3f4-4a12-be79-923bb03d7335Test
http://www.scopus.com/inward/record.url?scp=85133405965&partnerID=8YFLogxKTest

المؤلفون: van Merendonk, Lisanne N, Leeuwerik, Anke F, den Brok, Monique W J, Hekking, Pieter-Paul W, Korevaar, Daniel A, Jacobs, Christian J, Bet, Pierre M

المصدر: van Merendonk , L N , Leeuwerik , A F , den Brok , M W J , Hekking , P-P W , Korevaar , D A , Jacobs , C J & Bet , P M 2021 , ' Peripheral infiltration of remdesivir in 3 patients with COVID-19 : Case series and discussion ' , American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists , vol. 78 , no. 21 , pp. 1944-1951 . https://doi.org/10.1093/ajhp/zxab197Test

الوصف: PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic resulted in accelerated market access to remdesivir worldwide. Therefore, data about complications experienced during use of the drug are limited. This is the first published case series (1 case report exists) to describe remdesivir infiltration in 3 patients with COVID-19. SUMMARY: In the first case, a 91-year-old woman experienced remdesivir infiltration resulting in edema, hematoma at the area of infiltration; on palpation, the affected area felt cooler than the surrounding areas. Swelling was still present after 6 weeks. In the second case, remdesivir infiltration occurred in a 72-year-old male, resulting in edema, hematoma, and pain at the area of infiltration. The hematoma lasted for 7 days. The third case concerned a 67-year-old woman, in whom remdesivir infiltration led to edema and a small hematoma. The hematoma regressed to a negligible size within 3 days. However, a week after infiltration, redness had reappeared. In 2 cases, the patient was immediately treated with hyaluronidase injections, but no specific treatments were provided in the other case. CONCLUSION: Based on the product information provided by remdesivir's manufacturer, we believe symptoms and signs observed in the 3 cases may have resulted from the low pH (~4) of the nonbuffered remdesivir solution, although the patients were not formally assessed for caustic injury. Previous experience with other noncytotoxic medications suggests that infusion-specific factors (eg, volume of leaked fluid) and patient-specific factors (eg, advanced age) may have a role in the outcome of remdesivir infiltration. The possibility of symptoms caused by cyclodextrins in the formulation or by intrinsic toxicity of remdesivir warrants exploration.

العلاقة: https://research.vumc.nl/en/publications/40033545-193a-4343-8bcf-e44bd8853338Test

الإتاحة: https://doi.org/10.1093/ajhp/zxab197Test
https://research.vumc.nl/en/publications/40033545-193a-4343-8bcf-e44bd8853338Test
http://www.scopus.com/inward/record.url?scp=85116029430&partnerID=8YFLogxKTest

المؤلفون: Leeuwerik, A. F., van Merendonk, L. N., de Boer, M. A., Wilhelm, A. J., Kolkman, A., Bet, P. M.

المصدر: Leeuwerik , A F , van Merendonk , L N , de Boer , M A , Wilhelm , A J , Kolkman , A & Bet , P M 2023 , ' A new approach to drug intravenous compatibility research : The case of obstetric parenteral drugs ' , European Journal of Hospital Pharmacy . https://doi.org/10.1136/ejhpharm-2022-003577Test

الوصف: Objectives: The product information and literature does not provide confirmation of compatibility for co-administration of all commonly used drug pairs in obstetrics. However, there is a need for co-administration of these drugs over one lumen for this group of patients. Therefore, this study focuses on Y-site compatibility. Since different conditions between clinical and laboratory settings can lead to discrepancies in results, a novel approach for drug intravenous compatibility testing was designed to reflect clinical conditions. The aim was to study the compatibility of nine commonly used drug pairs in obstetrics and to evaluate the clinical value of the designed method. Methods: The clinical situation was reflected by using different temperature ranges (20°C and 37°C), actual Y-site flow ratios, clinically relevant drug pairs and an observation time of 120 min. The clinically relevant drugs pairs include atosiban, nicardipine, amoxicillin/clavulanic acid, oxytocin, remifentanil, labetalol and magnesium sulpfate. Drug pairs were visually assessed according to the European Pharmacopoeia (Ph. Eur.) and pH was measured. When incompatibility of a drug pair seemed likely based on literature review or observed abnormalities during visual assessment, subvisual analysis was performed using a particle counter. Y-site compatibility applied for drug pairs when no visual changes occurred or when no additional particles were formed during the observation time. Results: Eight of the nine combinations showed no visual changes or noticeable changes in pH during the observation time. The amoxicillin/clavulanic-acid-oxytocin combination showed a colour change at 37°C at the actual Y-site flow ratio. However, subvisual particle counting showed no formation of additional particles. Conclusions: Y-site compatibility was established for all tested drug pairs. The new clinical approach for analysing Y-site compatibility provides a high certainty of outcomes for clinical practice. In this way, clinical complications and use of ...

العلاقة: https://research.vumc.nl/en/publications/26e92c26-3659-4100-8491-95ab3ee8e8a5Test

الإتاحة: https://doi.org/10.1136/ejhpharm-2022-003577Test
https://research.vumc.nl/en/publications/26e92c26-3659-4100-8491-95ab3ee8e8a5Test
http://www.scopus.com/inward/record.url?scp=85152675509&partnerID=8YFLogxKTest

المؤلفون: van de Stadt, Eveline Annette, Yaqub, Maqsood, Schuit, Robert C., Bartelink, Imke H., Leeuwerik, Anke F., Schwarte, Lothar A., de Langen, Adrianus J., Hendrikse, Harry, Bahce, Idris

المصدر: Diagnostics (2075-4418); Apr2022, Vol. 12 Issue 4, p883-883, 15p

مصطلحات موضوعية: NON-small-cell lung carcinoma, EPIDERMAL growth factor receptors, CANCER patients, BRAIN tumors, PROTEIN-tyrosine kinase inhibitors, PHARMACOKINETICS

مستخلص: Background: Patients with non-small cell lung cancer (NSCLC) driven by activating epidermal growth factor receptor (EGFR) mutations are best treated with therapies targeting EGFR, i.e., tyrosine kinase inhibitors (TKI). Radiolabeled EGFR-TKI and PET have been investigated to study EGFR-TKI kinetics and its potential role as biomarker of response in NSCLC patients with EGFR mutations (EGFRm). In this study we aimed to compare the biodistribution and kinetics of three different EGFR-TKI, i.e., ¹¹C-erlotinib, ¹⁸F-afatinib and ¹¹C-osimertinib. Methods: Data of three prospective studies and 1 ongoing study were re-analysed; data from thirteen patients (EGFRm) were included for ¹¹C-erlotinib, seven patients for ¹⁸F-afatinib (EGFRm and EGFR wild type) and four patients for ¹¹C-osimertinib (EGFRm). From dynamic and static scans, SUV and tumor-to-blood (TBR) values were derived for tumor, lung, spleen, liver, vertebra and, if possible, brain tissue. AUC values were calculated using dynamic time-activity-curves. Parent fraction, plasma-to-blood ratio and SUV values were derived from arterial blood data. Tumor-to-lung contrast was calculated, as well as (background) noise to assess image quality. Results: ¹¹C-osimertinib showed the highest SUV and TBR (AUC) values in nearly all tissues. Spleen uptake was notably high for ¹¹C-osimertinib and to a lesser extent for ¹⁸F-afatinib. For EGFRm, ¹¹C-erlotinib and ¹⁸F-afatinib demonstrated the highest tumor-to-lung contrast, compared to an inverse contrast observed for ¹¹C-osimertinib. Tumor-to-lung contrast and spleen uptake of the three TKI ranked accordingly to the expected lysosomal sequestration. Conclusion: Comparison of biodistribution and tracer kinetics showed that ¹¹C-erlotinib and ¹⁸F-afatinib demonstrated the highest tumor-to-background contrast in EGFRm positive tumors. Image quality, based on contrast and noise analysis, was superior for ¹¹C-erlotinib and ¹⁸F-afatinib (EGFRm) scans compared to ¹¹C-osimertinib and ¹⁸F-afatinib (EGFR wild type) scans. [ABSTRACT FROM AUTHOR]

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المؤلفون: Merendonk, Lisanne N van¹ l.n.vanmerendonk@amsterdamumc.nl, Leeuwerik, Anke F¹, Brok, Monique W J den¹, Hekking, Pieter-Paul W², Korevaar, Daniel A², Jacobs, Christian J³, Bet, Pierre M¹

المصدر: American Journal of Health-System Pharmacy. Nov2021, Vol. 78 Issue 21, p1944-1951. 8p. 5 Color Photographs, 2 Charts.

مصطلحات موضوعية: *COVID-19, *HEMATOMA, *ANTIVIRAL agents, *TREATMENT effectiveness, *GLYCOSIDASES, *EXTRAVASATION, *EDEMA

مستخلص: Purpose The coronavirus disease 2019 (COVID-19) pandemic resulted in accelerated market access to remdesivir worldwide. Therefore, data about complications experienced during use of the drug are limited. This is the first published case series (1 case report exists) to describe remdesivir infiltration in 3 patients with COVID-19. Summary In the first case, a 91-year-old woman experienced remdesivir infiltration resulting in edema, hematoma at the area of infiltration; on palpation, the affected area felt cooler than the surrounding areas. Swelling was still present after 6 weeks. In the second case, remdesivir infiltration occurred in a 72-year-old male, resulting in edema, hematoma, and pain at the area of infiltration. The hematoma lasted for 7 days. The third case concerned a 67-year-old woman, in whom remdesivir infiltration led to edema and a small hematoma. The hematoma regressed to a negligible size within 3 days. However, a week after infiltration, redness had reappeared. In 2 cases, the patient was immediately treated with hyaluronidase injections, but no specific treatments were provided in the other case. Conclusion Based on the product information provided by remdesivir's manufacturer, we believe symptoms and signs observed in the 3 cases may have resulted from the low pH (~4) of the nonbuffered remdesivir solution, although the patients were not formally assessed for caustic injury. Previous experience with other noncytotoxic medications suggests that infusion-specific factors (eg, volume of leaked fluid) and patient-specific factors (eg, advanced age) may have a role in the outcome of remdesivir infiltration. The possibility of symptoms caused by cyclodextrins in the formulation or by intrinsic toxicity of remdesivir warrants exploration. [ABSTRACT FROM AUTHOR]

المؤلفون: Leeuwerik, J. F.

المصدر: Maandblad Voor Accountancy en Bedrijfseconomie 61((12)) 519-525

الوصف: Effecten van de Zevende EEG-Richtlijn op de consolidatieverplichting

العلاقة: https://zenodo.org/record/3392196Test; https://doi.org/10.5117/mab.61.13559Test; oai:zenodo.org:3392196

الإتاحة: https://doi.org/10.5117/mab.61.13559Test
https://zenodo.org/record/3392196Test