A5055085283- Renal Transplantation Outcomes and Treatments
- Organ Transplantation Techniques and Outcomes
- Liver Disease and Transplantation
- Pharmacological Effects and Toxicity Studies
- Liver Disease Diagnosis and Treatment
- Biochemical and Molecular Research
- Metabolism and Genetic Disorders
- Antibiotics Pharmacokinetics and Efficacy
- HIV/AIDS drug development and treatment
- Acute Lymphoblastic Leukemia research
- Adenosine and Purinergic Signaling
- Cancer Genomics and Diagnostics
- Transplantation: Methods and Outcomes
- Neurological Complications and Syndromes
- Pharmacogenetics and Drug Metabolism
- Pharmaceutical studies and practices
- Renal Diseases and Glomerulopathies
- Analytical Methods in Pharmaceuticals
- Bipolar Disorder and Treatment
- Cytomegalovirus and herpesvirus research
- Asthma and respiratory diseases
- Drug-Induced Hepatotoxicity and Protection
- Drug Transport and Resistance Mechanisms
- Pregnancy and Medication Impact
- Sepsis Diagnosis and Treatment
Universitätsmedizin Göttingen
2015-2025
University of Göttingen
2010-2024
University Medical Center
2024
Novartis (Switzerland)
2009-2016
Universitat de Barcelona
2016
Astellas Pharma (Netherlands)
2016
Siemens Healthcare (Germany)
2016
Hospital Central de las Fuerzas Armadas
2016
Goethe University Frankfurt
2016
Université Paris Cité
2016
In 2007, a consortium of European experts on tacrolimus (TAC) met to discuss the most recent advances in drug/dose optimization TAC taking into account specific clinical situations and analytical methods currently available drew some recommendations guidelines help clinicians with practical use drug. Pharmacokinetic, pharmacodynamic, more recently pharmacogenetic approaches aid physicians individualize long-term therapies as demonstrates high degree both between- within-individual...
BACKGROUND Cell-free DNA (cfDNA) from grafts in the circulation of transplant recipients is a potential biomarker rejection. Its usefulness was investigated after heart transplantation during maintenance phase by use microarrays and massive parallel sequencing donor recipient DNA. Disadvantages these methods are high costs, long turnaround times, need for Therefore, we sought to develop rapid cost-effective method using digital droplet PCR (ddPCR). METHODS Plasma samples were collected...
Background Graft-derived cell-free DNA (GcfDNA), which is released into the blood stream by necrotic and apoptotic cells, a promising noninvasive organ integrity biomarker. In liver transplantation (LTx), neither conventional function tests (LTFs) nor immunosuppressive drug monitoring are very effective for rejection monitoring. We therefore hypothesized that quantitative measurement of donor-derived (cfDNA) would have independent value assessment graft integrity, including damage from acute...
Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive biomarker for comprehensive monitoring of allograft injury and rejection in kidney transplantation (KTx). dd-cfDNA quantification copies/mL plasma (dd-cfDNA[cp/mL]) was compared to fraction (dd-cfDNA[%]) at prespecified visits 189 patients over 1 year post KTx. In (N = 15, n 22 samples) with biopsy-proven (BPR), median dd-cfDNA(cp/mL) 3.3-fold dd-cfDNA(%) 2.0-fold higher (82 cp/mL; 0.57%, respectively) than medians Stable Phase 83, 408)...
Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from patients with autoimmune disorders suggest that temporary MPA hold might greatly improve booster vaccination outcomes. We applied a fourth dose of vaccine to 29 kidney transplant during (5 weeks) MPA/azathioprine hold, who had not mounted humoral immune response previous vaccinations. Seroconversion until day 32 was observed...
It is currently being debated whether pharmacokinetic monitoring of mycophenolic acid (MPA), the active constituent mycophenolate mofetil (MMF), can optimize MMF therapy after organ transplantation. This open-label longitudinal study in pediatric renal transplant recipients was designed to investigate (PK)/pharmacodynamic relationship total and free MPA establish PK values for assessment an individual's parameters. Fifty-four children, aged 2.2 17.8 yr, on immunosuppressive triple regimen...
Fixed-dose mycophenolate mofetil (MMF) reduces the incidence of acute rejection after solid organ transplantation. The Fixed-Dose Concentration Controlled trial assessed feasibility and potential benefit therapeutic drug monitoring in patients receiving MMF de novo renal transplant.Patients were randomized to a concentration-controlled (n=452; target exposure 45 mg hr/L) or fixed-dose (n=449) MMF-containing regimen. primary endpoint was treatment failure (a composite biopsy-proven [BPAR],...
Abstract Background: A substantial proportion of the variability in absorption and clearance cyclosporin (CsA) after oral administration has been attributed to liver cytochrome P-450 3A4 (CYP3A4) activity intestinal P-glycoprotein (P-gp) concentration. polymorphism CYP3A4 promoter region, termed “variant” allele CYP3A4-V, was postulated be associated with altered enzyme activity. exon 26 (C3435T) multidrug resistance-1 (MDR-1) gene correlated expression vivo P-gp. Methods: We investigated...
Dosage guidelines for mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), are still preliminary in children. This study compares pharmacokinetics MPA and its major metabolite glucuronide (MPAG) pediatric renal transplant recipients receiving 600 mg MMF/m2 body surface area twice a day to those adults on currently recommended oral dose 1 g MMF day. Concentration-time profiles 18 children (age, 10.7+/-0.72 yr; range, 5.9 15.3 yr) 10 were investigated...
Tacrolimus is metabolized predominantly to 13-O-demethyltacrolimus in the liver and intestine by cytochrome P450 3A (CYP3A). Patients with high concentrations of CYP3A5, a CYP3A isoenzyme polymorphically produced these organs, require higher doses tacrolimus, but exact mechanism this association unknown.cDNA-expressed enzymes bank human microsomes known CYP3A4 CYP3A5 content were used investigate contribution metabolism tacrolimus as quantified liquid chromatography-tandem mass...
Mycophenolic acid (MPA), is primarily metabolized in the liver to 7‐O‐MPA‐β‐glucuronide (MPAG). Using RP‐h.p.l.c. we observed three further MPA metabolites, M‐1, M‐2, M‐3, plasma of transplant recipients on MMF therapy. To obtain information structure and source these metabolites: (A) h.p.l.c. fractions containing either metabolite or were collected analysed by tandem mass spectrometry; (B) metabolism was studied human microsomes presence UDP‐glucuronic acid, UDP‐glucose NADPH; (C)...
Background. Diarrhea is the most frequently reported adverse event in mycophenolate mofetil (MMF)-treated transplant patients. The aim of this study was to explore gastrointestinal tract MMF-treated renal recipients with persistent afebrile diarrhea characterize its nature and etiology. Methods. Renal (daily fecal output >200 g) were prospectively investigated for infections, morphologic, functional (gastrointestinal motility intestinal absorptive capacity) integrity tract; 26 patients met...
With the introduction of novel immunosuppressive agents sirolimus and everolimus, new, potentially more effective regimens are undergoing clinical evaluation. Whereas calcineurin inhibitors cyclosporin A (CsA) tacrolimus suppress early activation T lymphocytes through inhibition cytokines such as interleukin 2, primary target everolimus is mammalian rapamycin (mTOR), a specific cell-cycle regulatory protein. The mTOR leads to suppression cytokine-driven T-lymphocyte proliferation (1)....
Abstract Objective: Reduced numbers of regulatory T (T reg ) cells have been observed in visceral adipose tissue obese mice and humans. However, it is unknown whether human obesity affects circulating Treg their number associated with markers systemic inflammation or glucose intolerance. Design Methods: Peripheral blood mononuclear were isolated from venous (BMI ≥ 27 kg/m 2 ; n = 30) nonobese 13) individuals analyzed using flow cytometry for the expression CD4, CD25, Foxp3. Results: ‐cell...
In 2014, the Immunosuppressive Drugs Scientific Committee of International Association Therapeutic Drug Monitoring and Clinical Toxicology called a meeting international experts to provide recommendations guide therapeutic drug monitoring (TDM) everolimus (EVR) its optimal use in clinical practice. EVR is potent inhibitor mammalian target rapamycin, approved for prevention organ transplant rejection treatment various types cancer tuberous sclerosis complex. fulfills prerequisites TDM, having...