A5007239971- Renal Transplantation Outcomes and Treatments
- Hematopoietic Stem Cell Transplantation
- Lymphatic System and Diseases
- IL-33, ST2, and ILC Pathways
- Chronic Lymphocytic Leukemia Research
- Lysosomal Storage Disorders Research
- Hormonal and reproductive studies
- COVID-19 Clinical Research Studies
- Adrenal Hormones and Disorders
- 3D Printing in Biomedical Research
- Pharmacogenetics and Drug Metabolism
- Drug-Induced Ocular Toxicity
- Statistical Methods in Clinical Trials
- Chronic Myeloid Leukemia Treatments
- Acute Lymphoblastic Leukemia research
- Sexual Differentiation and Disorders
- Pharmacological Effects and Toxicity Studies
- Lymphatic Disorders and Treatments
- Calcium signaling and nucleotide metabolism
- Statistical Methods and Bayesian Inference
- Chemotherapy-induced organ toxicity mitigation
- Blood Pressure and Hypertension Studies
- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- RNA regulation and disease
University of Minnesota
2017-2024
Gilead Sciences (United States)
2023-2024
Minneapolis College
2022
Community Link
2020
Thrasher Research Fund
2020
Louisiana State University Health Sciences Center Shreveport
2014-2018
Hydroxychloroquine is an antimalarial drug being tested as a potential treatment for the novel coronavirus disease 2019 (COVID‐19) pandemic caused by severe acute respiratory syndrome 2. Although efficacy of hydroxychloroquine COVID‐19 remains uncertain, it may serve prophylactic agent especially in those at high risk, such healthcare workers, household contacts infected patients, and immunocompromised. Our aim was to identify possible dosing regimens through simulation risk infections...
Objectives: Mycophenolate mofetil (MMF) is a common immunosuppressant in transplantation. Mycophenolic acid (MPA), the active metabolite, undergoes enterohepatic circulation (EHC) characterized by secondary peak(s). The microbiome affects MPA exposure altering EHC through deglucuronidation of mycophenolic glucuronide (MPAG), an inactive but abundant metabolite[1]. While high dimensionality data presents challenge for incorporating it into population pharmacokinetic (PopPK) modeling,...
The aim of this study was to characterize the pharmacokinetic/pharmacodynamic relationships cortisol and adrenal biomarkers 17-hydroxyprogesterone androstenedione in children with congenital hyperplasia (CAH).A nonlinear mixed-effect modelling approach used analyse cortisol, concentrations obtained over 6 hours from CAH (n = 50). A circadian rhythm evident model leveraged literature information on untreated CAH. Indirect response models were applied which inhibited production rate all three...
Mycophenolate mofetil (MMF) is an important immunosuppressant used after allogeneic hematopoietic cell transplantation (HCT). MMF has a narrow therapeutic index, and blood concentrations of mycophenolic acid (MPA), the active component MMF, are highly variable. Low MPA associated with risk graft-versus-host disease (GVHD), whereas high toxicity. Reasons for variability not well known may include presence β-glucuronidase-producing bacteria in gastrointestinal tract, which enhance...
Background and Purpose The lymphatic system maintains tissue homeostasis by unidirectional lymph flow, maintained tonic phasic contractions within subunits, ‘lymphangions’. Here we have studied the effects of inflammatory cytokine IL ‐1β on contraction rat mesenteric muscle cells ( RMLMC ). Experimental Approach We measured in colon‐conditioned media CM ) from acute AC‐CM , dextran sodium sulfate) chronic CC‐CM T‐cell transfer) colitis‐induced mice corresponding controls C on‐ AC / examined...
Abstract The lymphatic system maintains tissue homeostasis by transporting interstitial fluid, lipids and debris from tissues to the main circulation, delivers antigen presenting cells local lymph nodes where they elicit immune responses. During inflammation, flow increases limit edema prevents antigen‐presenting cell transport. Lymphatics also adjust their contractile activity increase fluid transfer during acute inflammation. Conversely, chronic inflammation can provoke lymphostasis, which...
Nano-engineered mesenchymal stem cells (nano-MSCs) are promising targeted drug delivery platforms for treating solid tumors. MSCs engineered with paclitaxel (PTX) loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) efficacious in lung and ovarian tumors mouse models. The quantitative description of pharmacokinetics (PK) pharmacodynamics (PD) nano-MSCs is crucial optimizing their therapeutic efficacy clinical translatability. However, successful translation challenging due to complex...
Theiler's murine encephalomyelitis virus (TMEV) induces different diseases in the central nervous system (CNS) and heart, depending on mouse strains time course, with cytokines playing key roles for viral clearance immune-mediated pathology (immunopathology) both cases. In SJL/J mice, TMEV infection causes chronic TMEV-induced demyelinating disease (TMEV-IDD) spinal cord at about 1 month post inoculation (p.i.). Unlike other immunopathology models, pro- anti-inflammatory can play dual...
Abstract Aims Tacrolimus, metabolized by CYP3A4 and CYP3A5 enzymes, is susceptible to drug–drug interactions (DDI). Steroids induce CYP3A genes increase tacrolimus clearance, but the effect variable. We hypothesized that extent of steroid–tacrolimus DDI differs CYP3A4/5 genotypes. Methods Kidney transplant recipients ( n = 2462) were classified number loss function alleles (LOF) CYP3A5*3 , *6 *7 CYP3A4*22 ) steroid use at each trough in first 6 months post‐transplant. A population...
Placental vascular dysfunction has been linked to insufficiency/deficiency of maternal vitamin D levels during pregnancy. In contrast, sufficient have shown beneficial effects on pregnancy outcomes. To study the role in pregnancy, we tested our hypothesis that exerts placental vasculature. We examined expression CYP2R1, CYP27B1, receptor (VDR), and CYP24A1 smooth muscle cells (VSMCs) response 1,25(OH)2D3 found VDR was inducible, CYP27B1 dose-dependently down-regulated, up-regulated treated...
Eliglustat is a glucosylceramide synthase inhibitor indicated as long-term substrate reduction therapy for adults with type 1 Gaucher disease, lysosomal rare disease. It primarily metabolized by cytochrome P450 2D6 (CYP2D6), and variants in the gene encoding this enzyme are important determinants of eliglustat pharmacokinetics (PK) drug-drug interactions (DDIs). The existing drug label addresses DDIs to some extent but has omitted scenarios where both metabolizing CYPs (2D6 3A4) mildly or...
To evaluate bupivacaine concentrations in maternal plasma and transfer into breast milk women undergoing liposomal infiltration the transversus abdominis plane after cesarean birth.Prospective cohort study of healthy pregnant who underwent birth at term followed by a block using 52 mg hydrochloride 0.25% (20 mL) 266 1.3% mL). Simultaneous blood samples were collected staggered fashion, three to four per patient following timepoints administration: 2, 6, 12, 24, 48, 72, 96 hours....
Absorption processes are complex but rarely have sufficient data to capture parameters of a mechanistic model. Typically, single absorption model (e.g., first-order, mixed-order, lag, or distributive delay model), is assumed apply all individuals with the expectation that random effects will accommodate individual differences. However, distinct profiles may coexist in given dataset. We propose individualized models should be considered when multiple evident population analysis....
Abstract Genetic variation in the CYP3A4 and CYP3A5 (CYP3A4/5) genes, which encode key enzymes tacrolimus metabolism, is associated with clearance dose requirements. Tacrolimus has a narrow therapeutic index high intra‐ intersubject variability, part because of genetic variation. High low trough concentration are greater risk for rejection, whereas troughs calcineurin‐induced toxicity. The objective this study was to develop model dosing equation accounting genotypes clinical factors adult...
Atomoxetine (ATX) is a non‐stimulant used to treat attention‐deficit/hyperactivity disorder (ADHD) and systemic exposure highly variable due polymorphic cytochrome P450 2D6 (CYP2D6) activity. The objective of this study was characterize the time course ATX metabolites (4‐hydroxyatomoxetine (4‐OH); N ‐desmethylatomoxetine (NDA); 2‐carboxymethylatomoxetine (2‐COOH)) following oral dosing in children with ADHD support individualized dosing. A nonlinear mixed‐effect modeling approach analyze...
Background: Therapeutic drug monitoring for mycophenolic acid (MPA) is challenging due to difficulties in measuring the area under curve (AUC). Limited sampling strategies (LSSs) have been developed MPA therapeutic but come with risk of unacceptable performance. The authors hypothesized that poor predictive performance LSSs were variability enterohepatic recirculation (EHR). This study first evaluate models context EHR. Methods: Adult kidney transplant recipients (n = 84) receiving oral...
Phosphoramide mustard (PM) is the final cytotoxic metabolite formed from parent compound cyclophosphamide through a complex metabolic pathway, primarily hepatic metabolism. Little known about effect of renal elimination on disposition PM. We evaluated function PM exposure after single doses in 85 patients undergoing allogeneic hematopoietic cell transplantation using nonlinear mixed-effects modeling. Mixed linear and pathways were required to adequately describe Creatinine clearance (CrCL)...
Cyclophosphamide (CY) is an alkylating agent widely used in the field of oncology and hematopoietic cell transplantation (HCT). It recommended to use adjusted body weight with adjustment factor 0.25 (ABW25) for dosing CY obese patients undergoing HCT. However, evidence based on pharmacokinetics (PK) support this recommendation lacking. We aimed identify a strategy that achieves equivalent exposures among nonobese patients. The present study secondary analysis previously conducted...
Summary In most drug development settings, the regulatory approval process is accompanied by extensive studies performed to understand drug's pharmacokinetic (PK) and pharmacodynamic (PD) properties. this article, we attempt utilize rich PK/PD data inform borrowing of information from adults during pediatric development. it especially crucial that are parsimonious with patients recruited for experimentation. We illustrate our approaches in context clinical trials cinacalcet treating...
Lysosomal diseases are a group of over 70 rare genetic conditions in which protein deficiency (most often an enzyme deficiency) leads to multi-system disease. Current therapies for lysosomal limited their ability treat certain tissues that major contributors morbidity and mortality, such as the central nervous system (CNS) cardiac valves. For this study, disease mucopolysaccharidosis type I (MPS I) was selected model. In MPS I, mutations IDUA gene cause α-L-iduronidase (IDUA) activity,...