Publications by authors named "Robert A M op den Buijsch"

Article Synopsis
  • * DNA was isolated from EDTA blood samples of renal transplant recipients and compared with those from dried blood spots on filter paper from healthy volunteers using three different methods.
  • * Results showed that DNA extracted via the column method matched perfectly with those from the DBS procedure, indicating that filter paper DNA isolation could be an effective alternative to traditional methods.
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Objective: In literature, a great diversity of limited sampling strategies (LSS) have been recommended for tacrolimus monitoring, however proper validation of these strategies to accurately predict the area under the time concentration curve (AUC0-12) is limited. The aim of this study was to determine whether these LSS might be useful for AUC prediction of other patient populations.

Methods: The LSS from literature studied were based on regression equations or on Bayesian fitting using MWPHARM 3.

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Tacrolimus, an immunosuppressant used after organ transplantation, has a narrow therapeutic range and its pharmacokinetic variability complicates its daily dose assessment. P-glycoprotein (P-gp), encoded by the adenosine triphosphate-binding cassette B1 (ABCB1) and the cytochrome (CYP) 3A4 and 3A5 enzymes appears to play a role in the tacrolimus metabolism. In the present study, two different renal transplant recipient groups were used to examine the influence of ABCB1 and CYP3A polymorphisms on the daily tacrolimus dose and several pharmacokinetic parameters.

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Article Synopsis
  • Tacrolimus has a narrow therapeutic window and its effectiveness varies greatly among individuals due to genetic differences.
  • This study explored how genetic variations in the CYP3A and ABCB1 genes affect the drug's concentration in the body, focusing on a specific group of 103 Chinese renal transplant recipients.
  • The research found that the CYP3A5*3 genetic variation significantly impacted the required dose of tacrolimus, suggesting that personalized genetic testing can optimize dosage for better immunosuppression outcomes.
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The polymorphisms (OATP)1B1 A388G and T521C of the solute carrier organic anion-transporter family member 1B1 gene (SLCO1B1), previously known as OATP-C, have potential impacts on drug metabolism. In order to establish a fast and consistent assay for these polymorphisms, rapid speed polymerase chain reaction (PCR) fluorescence resonance energy transfer (FRET) assays on the LightCycler were developed for both OATP1B1 polymorphisms. A locked nucleic acid (LNA) on the polymorphic location within the sensor probe was necessary to discriminate both alleles of the OATP1B1 T521C polymorphism.

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We describe the application of capillary electrophoresis to detect DNA fragments, obtained after amplifying a part of the apolipoprotein E (apoE) gene with polymerase chain reaction (PCR). Compared to conventional agarose slab gel electrophoresis (AGE), CE appears the method of choice with regard to resolution and sensitivity, to detect DNA fragments in the range of 20-100 base pairs. Especially discrimination between apoE2/E2 and apoE2/E3 genotypes is more reliable with CE than with AGE, this being of great clinical value in the diagnosis of familiary dysbetalipoproteinemia.

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