A5059043089- Pregnancy and Medication Impact
- Pregnancy and preeclampsia studies
- COVID-19 Clinical Research Studies
- Drug Transport and Resistance Mechanisms
- Cannabis and Cannabinoid Research
- SARS-CoV-2 and COVID-19 Research
- Alcohol Consumption and Health Effects
- Neonatal Respiratory Health Research
- Cardiac electrophysiology and arrhythmias
- HIV Research and Treatment
- Pharmacological Effects and Toxicity Studies
- Respiratory viral infections research
- Cancer therapeutics and mechanisms
- Tuberculosis Research and Epidemiology
- Biochemical and Molecular Research
- Childhood Cancer Survivors' Quality of Life
- Epilepsy research and treatment
- Prenatal Substance Exposure Effects
- SARS-CoV-2 detection and testing
- HIV/AIDS Research and Interventions
- Metabolomics and Mass Spectrometry Studies
- Birth, Development, and Health
- Inhalation and Respiratory Drug Delivery
- Antibiotics Pharmacokinetics and Efficacy
- HIV/AIDS drug development and treatment
Gilead Sciences (United States)
2022-2025
University of Washington
2018-2022
Infectious Disease Research Institute
2021
Seattle University
2021
Lenacapavir (LEN) is a first-in-class inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function in clinical development for the treatment heavily treatment-experienced (HTE) people with HIV (PWH) harboring multidrug resistance (MDR) combination an optimized background regimen (OBR). Here we describe analyses conducted pivotal phase 2/3 CAPELLA study.CAPELLA enrolled viremic HTE PWH to ≥3 4 main antiretroviral (ARV) classes and ≥2 ARV drugs per class. Baseline used commercial...
Some women take medication during pregnancy to address a variety of clinical conditions. Because ethical and logistical concerns, it is impossible determine fetal drug exposure, therefore risk, pregnancy. Hence, alternative approaches need be developed predict maternal-fetal exposure throughout To do so, we previously verified physiologically based pharmacokinetic model, which can drugs that passively cross the placenta. However, many are actively transported by placenta (e.g., human...
Many women take drugs during their pregnancy to treat a variety of clinical conditions. To optimize drug efficacy and reduce fetal toxicity, it is important determine or predict exposure throughout pregnancy. Previously, we developed verified maternal-fetal physiologically based pharmacokinetic (m-f PBPK) model K<sub>p,uu</sub> (unbound plasma AUC/unbound maternal AUC) that passively cross the placenta. Here, used in vitro transport studies Transwell, combination with our m-f PBPK model, are...
Abstract Background Remdesivir (RDV) is an intravenous nucleotide prodrug approved for COVID-19 treatment. Its effect on QT interval unknown. This Phase 1 study evaluated the effects of a supratherapeutic dose RDV interval.Figure 1.Estimated ΔΔQTcF (90% CI) between and Placebo-to-match RDV.ΔΔQTcF, baseline-adjusted, placebo-matched QTcF; QTcF, corrected heart rate using Fridericia formula; RDV, remdesivir. Methods included 2 cohorts healthy participants aged 18-55 years: dose-selection...
In order to optimize central nervous system (CNS) drug development, accurate prediction of the drug's human steady-state unbound brain interstitial fluid-to-plasma concentration ratio (Kp,uu,brain ) is critical, especially for drugs that are effluxed by multiple resistance transporters (e.g., P-glycoprotein, P-gp). Due lack good in vitro blood-brain barrier models, we and others have advocated use a proteomics-informed relative expressive factor (REF) approach predict Kp,uu,brain ....
There is an unmet need for safe and efficacious oral therapies COVID-19 with low potential drug-drug interactions. Obeldesivir orally administered nucleoside prodrug that has shown antiviral potency in nonclinical studies against SARS-CoV-2 its circulating variants. metabolized to the active triphosphate (GS-443902), which acts as inhibitor of RNA-dependent RNA polymerase, thereby inhibiting viral synthesis. Here, we report safety, tolerability, pharmacokinetics from a first-in-human,...
Marijuana use by pregnant women is increasing. To predict developmental risk to the fetus/neonate from such use, in utero fetal exposure (−)-∆<sup>9</sup>-tetrahydrocannabinol (THC), main psychoactive cannabinoid marijuana and its active metabolite, 11-hydroxy-∆<sup>9</sup>-tetrahydrocannabinol (11-OH-THC), needs be determined. Since measurement not possible, physiologically based pharmacokinetic (PBPK) modeling simulation can provide an alternative method estimate cannabinoids. do so,...
(−)-Δ<sup>9</sup>-Tetrahydrocannabinol (THC) is the psychoactive constituent of cannabis, a drug recreationally consumed orally or by inhalation. Physiologically based pharmacokinetic (PBPK) modeling can be used to predict systemic and tissue exposure THC its metabolite, (±)-11-hydroxy-Δ<sup>9</sup>-THC (11-OH-THC). To populate THC/11-OH-THC PBPK model, we previously characterized depletion clearance (by CYP2C9) 11-OH-THC UDP-glucuronosyltransferase (UGT), CYP3A, in adult human liver...
Intravenous remdesivir (RDV) is US Food and Drug Administration-approved for hospitalized nonhospitalized individuals with coronavirus disease 2019. RDV undergoes intracellular metabolic activation to form the active triphosphate, GS-443902, other metabolites. Alternative administration routes, including localized pulmonary delivery, can lower systemic exposure maximize at site of action. This study evaluated pharmacokinetics (PK) safety inhaled in healthy adults. phase Ia, randomized,...
We have previously developed a maternal-fetal physiologically-based pharmacokinetic (m-f PBPK) model to dynamically predict (and verify) fetal-maternal exposure drugs that passively diffuse across the placenta. Here, we extended application of this fetal which are effluxed by placental P-glycoprotein, namely antenatal corticosteroids (ACS; dexamethasone [DEX], and betamethasone [BET]). To do so, estimated both P-gp mediated efflux clearance (CL) passive diffusion CL ACS. The efficacy...
Abstract Background Remdesivir (RDV, Veklury) is the first FDA-approved direct-acting antiviral treatment for COVID-19. While RDV requires IV administration, obeldesivir (ODV, GS-5245) an oral prodrug of GS-441524, parent nucleoside RDV, designed effective delivery. ODV being tested in two Phase 3 clinical studies outpatient Methods In vitro activity against SARS-CoV-2 was assessed A549-hACE2 cells. vivo therapeutic efficacy evaluated mouse, ferret, and African Green Monkey (AGM) models....
The identification and development of new anti-tubercular agents are a priority research area. We identified the trifluoromethyl pyrimidinone series compounds in whole-cell screen against Mycobacterium tuberculosis . Fifteen primary hits had minimum inhibitory concentrations (MICs) with good potency IC 90 is concentration at which M. growth inhibited by 90% (IC &lt; 5 μM). conducted structure–activity relationship investigation for this series. designed synthesized an additional 44...
Introduction Respiratory distress syndrome is one of the major causes newborn deaths. Dexamethasone (DEX) and Betamethasone (BET) may promote fetal lung maturation when administered to pregnant women at risk preterm birth. Usually, DEX‐phosphate (6 mg) IM q 12 hrs over 48 while BET as a 50:50 phosphate acetate combination (12 mg total) 24 hrs. Recent non‐clinical trials suggest lower concentration would result in effective treatment for these drugs. In sheep, plasma concentrations >1...