A5031890270- Drug Transport and Resistance Mechanisms
- Pharmacogenetics and Drug Metabolism
- Pharmacological Effects and Toxicity Studies
- HIV/AIDS drug development and treatment
- Antibiotics Pharmacokinetics and Efficacy
- Antifungal resistance and susceptibility
- Cancer therapeutics and mechanisms
- Estrogen and related hormone effects
- Drug-Induced Hepatotoxicity and Protection
- Multiple Myeloma Research and Treatments
- Hepatitis B Virus Studies
- Pregnancy and Medication Impact
- Amino Acid Enzymes and Metabolism
- HIV Research and Treatment
- Nitric Oxide and Endothelin Effects
- Renin-Angiotensin System Studies
- Ubiquitin and proteasome pathways
- Cholesterol and Lipid Metabolism
- RNA Interference and Gene Delivery
- Ion Transport and Channel Regulation
- Eicosanoids and Hypertension Pharmacology
- Hormonal Regulation and Hypertension
- Liver Disease Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Molecular Biology Techniques and Applications
Heidelberg University
2016-2025
University Hospital Heidelberg
2016-2025
German Center for Infection Research
2017-2023
Brigham and Women's Hospital
2020
Harvard University
2020
Dana-Farber Brigham Cancer Center
2020
Dana-Farber Cancer Institute
2020
Pharmac
2017
Luzerner Kantonsspital
2017
Deutsche Forschungsgemeinschaft
2016
A multiplex PCR (M-PCR) assay with colorimetric detection was devised for the simultaneous amplification of DNA targets from Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV) types 1 2. By using target-specific oligonucleotides in a microwell format, 298 genital ulcer swab specimens collected New Orleans during three intervals 1992 through 1994 were evaluated. The results M-PCR compared dark-field microscopy H. ducreyi culture on two different media. HSV available 99...
Pharmacokinetic drug-drug interactions often occur at the level of P-glycoprotein (Pgp). To study possible caused by newer antidepressants we investigated citalopram, fluoxetine, fluvoxamine, paroxetine, reboxetine, sertraline, and venlafaxine their major metabolites desmethylcitalopram, norfluoxetine, paroxetine-metabolite (paroxetine-M), desmethylsertraline,<i>N</i>-desmethylvenlafaxine, and<i>O</i>-desmethylvenlafaxine for ability to inhibit Pgp. Pgp inhibition was studied a fluorometric...
Infection with enterotoxigenic Escherichia coli (ETEC) is a common cause of diarrhea among travelers and residents developing countries. ETEC produces either heat-stable toxin or heat-labile toxin, both, encoded by plasmid-borne ST LT genes, respectively. Diagnosis infection this subclass E. can be performed oligonucleotide hybridization probes; however, the sensitivity specificity method are insufficient. A nonradioactive multiplex PCR assay that provides sensitive specific for detecting...
The safety and effectiveness of highly active antiretroviral therapy (HAART) is challenged by viral resistance to antiretrovirals the frequent occurrence drug interactions which may limit access these drugs target sites. In particular, distribution elimination be modified efflux transporters. While P-glycoprotein well evaluated in this regard, interaction with ABC transporter BCRP (ABCG2) far from being elucidated. aim study was therefore investigate influence all important anti-HIV on...
In vitro data on the metabolism of antifungal voriconazole suggest that its pharmacokinetics might be influenced by activity CYP2C19, CYP2C9, and CYP3A. To elucidate genetic influence polymorphic enzymes metabolism, authors pooled pharmacokinetic from 2 interaction studies in which 35 participants were enrolled according to their CYP2C19 genotype receive a single 400-mg oral dose voriconazole. Nine homozygous for CYP2C19(*)1/(*)1, 8 heterozygous (*)1/(*)17, 11 (*)1/(*)2, (*)2/(*)17, 4...
* Pharmacokinetic variability of voriconazole is largely caused by CYP3A4- and CYP2C19-mediated metabolism. Oral bioavailability has been claimed to be almost 100%, thus facilitating a change from intravenous oral application without dose adjustment.* For the first time exposure after administration in relation CYP2C19 activity reported. In addition, predominant metabolic pathway hydroxylation that seems influenced genotype. Enterohepatic circulation both hydroxylated metabolites must...
Background/Objectives: Bempedoic acid (BA) is a novel cholesterol-lowering agent with proven positive effects on cardiovascular endpoints. Because it an inhibitor of the hepatic transporters OATP1B1 and OATP1B3, two uptake regulating intrahepatic availability statins, increases systemic exposure co-administered statins. This interaction could raise risk myopathy. We hypothesized that drug between BA statins be mitigated by staggered administration. Methods: was single-centre, open-label,...
A multiplex polymerase chain reaction (M-PCR) assay for Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV) was compared with clinical standard laboratory methods the diagnosis of genital ulcer disease (GUD) in 105 patients; 36% were human immunodeficiency (HIV)-seropositive. Chancroid (80%), syphilis (8%), (8%) most frequent diagnoses. H. ducreyi HSV isolated from ulcers 43% 18% patients, respectively; 35%, all cultures negative indeterminate. M-PCR detected T. 56%, 23%,...
Cytochrome P450 (CYP) 2C19 and CYP3A4 are the major enzymes responsible for voriconazole elimination. Because activity of CYP2C19 is under genetic control, extent inhibition with a inhibitor was expected to be modulated by metabolizer status. This study thus assessed effect potent ritonavir after short-term administration on pharmacokinetics in extensive metabolizers (EMs) poor (PMs) CYP2C19.In randomized, placebo-controlled crossover study, 20 healthy participants who were stratified...
Objectives Constituents of St John's wort (SJW) in vivo induce the cytochrome P450 (CYP) isozymes 3A4, 2C9, and 2C19 but vitro were shown to inhibit them. This study investigates both short- long-term effects SJW on antifungal voriconazole, which is metabolized by these enzymes. Methods In a controlled, open-label study, single oral doses 400 mg voriconazole administered 16 healthy men stratified for CYP2C19 genotype before day 1 15 concomitant intake (300 LI 160 3 times daily). Plasma urine...
Aims A clinically important interaction between the cardiac glycoside digoxin and antibiotic clarithromycin has been suggested in earlier reports. The aim of this study was to investigate extent relative contribution different mechanisms. Methods In a randomized, placebo‐controlled, double‐blind cross‐over design single oral doses 0.75 mg with coadministration placebo or 250 twice daily for 3 days were administered 12 healthy men. Additionally, three subjects received intravenous 0.01 kg −1...
Many drug interactions with drugs used for the therapy of human immunodeficiency virus (HIV) occur at level different cytochrome P450 isozymes. Increasing evidence suggests that antiretrovirals may also modify activity and expression active transport systems. Such alter absorption, elimination, distribution reach clinical importance if thereby access to target site is affected. Beyond P-glycoprotein, family multidrug resistance-related proteins (MRP/ABCC) substantially contributes...
About one-third of epilepsy patients are resistant to treatment with antiepileptic drugs (AEDs). This refractoriness is not fully understood, but thought be attributed overexpression multidrug transporters at the blood-brain barrier, particularly P-glycoprotein (Pgp). In certain cases pharmacoresistance can overcome by add-on therapy, raising question whether coadministered act as inhibitors Pgp. Indeed, several AEDs substrates and some extent also inducers To date nothing known about...
Breast cancer resistance protein (BCRP/ABCG2) is an active efflux pump that belongs to the ATP-binding cassette (ABC) transporter family. It located in various tissues involved drug absorption, distribution, and elimination plays important role multidrug resistance. For P-glycoprotein, another member of ABC family, it well established at least partly cholesterol sphingolipid-enriched domains plasma membrane called “lipid rafts” composition lipids may modulate its activity. This study...
The objective of the study was to establish an in vivo method for assessing cytochrome P450 3A (CYP3A) activity using therapeutically inert nanogram doses midazolam. We administered four escalating single oral midazolam (0.0001–3 mg) 12 healthy participants, stratified according CYP3A5 carrier status, assess pharmacokinetics linearity. then evaluated interactions with CYP3A inhibitor ketoconazole (400 mg q.d.) after and regular Area under plasma concentration–time curve (AUC) peak...
Myrcludex B acts as a hepatitis and D virus entry inhibitor blocking the sodium taurocholate cotransporting polypeptide (SLC10A1). We investigated effects of myrcludex on plasma bile acid disposition, tenofovir pharmacokinetics, perpetrator characteristics cytochrome P450 (CYP) 3A. Twelve healthy volunteers received 300 mg disoproxil fumarate orally 10 subcutaneous B. increased total exposure 19.2‐fold without signs cholestasis. The rise in conjugated acids was up to 124‐fold (taurocholic...
The drug transporter P-glycoprotein (ABCB1) plays an important role in distribution and elimination, when overexpressed it may confer multidrug resistance (MDR). is localized the plasma membrane, especially within rafts caveolae, characterized as detergent-resistant membranes (DRMs). This study investigated effect of cholesterol depletion repletion well saturation on subcellular localization function to determine DRM P-glycoprotein-mediated efflux. In L-MDR1 overexpressing human...