A5051243110- HIV/AIDS drug development and treatment
- Hepatitis C virus research
- Hepatitis B Virus Studies
- HIV Research and Treatment
- Colorectal Cancer Treatments and Studies
- HIV/AIDS Research and Interventions
- Pneumocystis jirovecii pneumonia detection and treatment
- Antifungal resistance and susceptibility
- Renal Transplantation Outcomes and Treatments
- Cancer Genomics and Diagnostics
- Gastric Cancer Management and Outcomes
- Liver Disease Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- HER2/EGFR in Cancer Research
- Cancer Treatment and Pharmacology
- Lung Cancer Treatments and Mutations
- Pharmacological Effects and Toxicity Studies
- Influenza Virus Research Studies
- Antibiotics Pharmacokinetics and Efficacy
- Intramuscular injections and effects
- Botulinum Toxin and Related Neurological Disorders
- Cystic Fibrosis Research Advances
- Viral-associated cancers and disorders
- Peptidase Inhibition and Analysis
- PI3K/AKT/mTOR signaling in cancer
GlaxoSmithKline (United States)
2016-2025
Kalamazoo College
2023-2024
ChiangRai Prachanukroh Hospital
2024
John Wiley & Sons (United States)
2022
Hudson Institute
2022
Research Triangle Park Foundation
2019
Dana-Farber Cancer Institute
2013-2015
Palo Alto University
2015
Stanford University
2015
DKFZ-ZMBH Alliance
2013-2015
Abstract Background Previously reported post hoc multivariable analyses exploring predictors of confirmed virologic failure (CVF) with cabotegravir + rilpivirine long-acting (CAB RPV LA) were expanded to include data beyond week 48, additional covariates, and participants. Methods Pooled from 1651 participants used explore dosing regimen (every 4 or every 8 weeks), demographic, viral, pharmacokinetic covariates as potential CVF. Prior experience was accounted for using 2 populations. Two...
To assess new metrics of tumor-size response to predict overall survival (OS) in colorectal cancer (CRC) Western and Chinese patients.Various were estimated using longitudinal tumor size models data from two phase III studies that compared bevacizumab plus chemotherapy versus as first-line therapy (n = 923) 203) patients with CRC. Baseline prognostic factors estimates assessed multivariate OS. Predictive performances the by simulating multiple replicas studies.Time growth (TTG) was best...
ABSTRACT This study was undertaken to characterize the pharmacokinetics and bioavailability of voriconazole in adult lung transplant patients during early postoperative period, identify factors significantly associated with various pharmacokinetic parameters, make recommendations for adequate dosing regimens. Thirteen received two intravenous infusions (6 mg/kg, twice daily [b.i.d.]) immediately posttransplant followed by oral doses (200 mg, b.i.d.) prophylaxis. Blood samples (9/interval)...
To characterize cabotegravir population pharmacokinetics using data from phase 1, 2 and 3 studies evaluate the association of intrinsic extrinsic factors with pharmacokinetic variability.Analyses were implemented in NONMEM R. Concentrations below quantitation limit modelled likelihood-based approaches. Covariate relationships evaluated forward addition (P < .01) backward elimination .001) The impact each covariate on trough peak concentrations was through simulations. External validation...
The mammalian target of rapamycin is activated in Kaposi sarcoma (KS) and its inhibitor, rapamycin, has induced KS regression transplant-associated KS. This study aimed to evaluate rapamycin's safety toxicity HIV-infected individuals with receiving antiretroviral therapy (ART), investigate interactions both protease inhibitor (PI)-containing nonnucleoside reverse transcriptase (NNRTI)-containing ART regimens, assess clinical biological endpoints including response rapamycin-dependent...
Bevacizumab is approved for various cancers. This analysis aimed to comprehensively evaluate bevacizumab pharmacokinetics and the influence of patient variables on pharmacokinetics. Rich sparse serum concentrations were collected from Phase I through IV studies in early metastatic was given intravenously as single agent or combination with chemotherapy single- multiple-dose schedules. Model-building used 8943 1792 patients colon/colorectal, non-small cell lung, kidney, pancreatic, breast,...
Altered pharmacokinetics of antibody drugs has been reported in advanced gastric cancer (AGC). We aim to evaluate bevacizumab AGC from the Phase III trial (AVAGAST), and explore influence patient variables. Bevacizumab concentrations (Cp) were measured plasma samples taken following disease progression 162 patients (7.5 mg/kg every 3 weeks). Predicted Cp [median 90% prediction interval] was simulated using population pharmacokinetic model established for other cancers (PPK model) compared...
Abstract GSK3389404 is a liver‐targeted antisense oligonucleotide that inhibits synthesis of hepatitis B surface antigen and all other virus proteins. This first‐in‐human, randomized, double‐blind, phase 1 study assessed the safety pharmacokinetics administered subcutaneously (SC) in healthy subjects. Four single ascending‐dose cohorts (10 mg, 30 60 120 mg) 3 multiple (30 mg once weekly for 4 weeks) each comprised 6 subjects randomized to 2 placebo. There were no serious adverse events (AEs)...
Cabotegravir + rilpivirine administered via intramuscular gluteal injections is the first complete long-acting (LA) regimen approved for maintaining HIV-1 virologic suppression. The
ABSTRACT Long-acting cabotegravir is approved for pre-exposure prophylaxis and combination HIV treatment, both initiated with optional short-term oral lead-in (OLI). We evaluated the impact of OLI on long-acting pharmacokinetics. Cabotegravir plasma concentrations were compared between HIV-positive participants initiating injections ( n = 278) or without 110) in phase III treatment study FLAIR HIV-negative using 263) pivotal studies HPTN 083 084. pharmacokinetic profiles simulated three...
The aim of the present study was to evaluate pharmacokinetics bevacizumab and various dosing strategies for this agent in paediatric patients.Data were collected from 232 patients (1971 concentrations) five studies, with a wide range age (0.5-21 years), body weight (BWT; 5.9-125 kg), regimens (5-15 mg kg(-1) biweekly or triweekly). Data 152 (1427 80 (544 used model building external validation, respectively. Steady-state exposure simulated under BWT-based, surface area (BSA)-based, ideal...
Single-visit cures for chronic hepatitis C are lacking. We conducted two clinical studies towards the goal of developing a regimen single-visit cure. In randomized, open-label, Phase 2 study (RG101-04), investigators enrolled 26 adult patients to evaluate safety and efficacy single subcutaneous injection RG-101 (4 mg/kg) daily oral tablets GSK2878175 (20 mg) 6, 9 or 12 weeks. another double-blind, dose 1 (RG101-06), 18 healthy men assess PK long-acting injectable at 100, 200 400 mg....
Abstract Background Cabotegravir + rilpivirine (CAB RPV) administered via intramuscular gluteal injections is the first complete long-acting regimen for maintaining human immunodeficiency virus type 1 (HIV-1) virologic suppression. We present substudy results on short-term repeat CAB RPV thigh in participants with ≥3 years of experience administration during ATLAS–2M study. Methods Substudy phases included screening, injection (day 1–week 16), and return to (week 16–week 24). The schedule...
Bepirovirsen is an antisense oligonucleotide currently in Phase 3 development to treat chronic hepatitis B virus (HBV) infection. Given the importance of coadministration bepirovirsen and standard-of-care nucleos(t)ide analogs (NAs), we evaluated drug-drug interactions (DDIs) between bepirovirsen, entecavir (ETV), tenofovir (TFV) using vitro clinical data obtained through innovative study design sampling strategy. Static models employing indicated that not a direct inhibitor or inducer most...
Abstract Long‐acting (LA) cabotegravir 200‐mg/mL (CAB200) injections are approved for HIV‐1 prevention and as a complete LA treatment regimen with rilpivirine. A high‐concentration suspension formulation, 400 mg/mL (CAB400‐D), was developed to enable less frequent dosing self‐administration. This phase 1, double‐blind, randomized study (NCT04484337) evaluated intramuscular (IM) gluteal, subcutaneous (SC) abdominal, IM thigh CAB400‐D (200‐800 mg [0.5‐2.0 mL]) in adults without HIV, using...
The objective of this study was to evaluate the pharmacokinetics voriconazole and potential correlations between pharmacokinetic parameters patient variables in liver transplant patients on a fixed-dose prophylactic regimen. Multiple blood samples were collected within one dosing interval from 15 who initiated regimen at 200 mg enterally (tablets) twice daily starting immediately posttransplant. Voriconazole plasma concentrations measured using high-pressure liquid chromatography (HPLC)....
Physiological changes in pregnancy are expected to alter the pharmacokinetics of various drugs. The objective this study was evaluate systematically oseltamivir (OS), a drug used treatment influenza during pregnancy.A multicentre steady-state pharmacokinetic OS performed 35 non-pregnant and 29 pregnant women. Plasma concentration-time profiles were analyzed using both non-compartmental population modelling (pop PK) simulation approaches. A one compartment model with first order absorption...
Aim Cabotegravir long‐acting (LA) intramuscular (IM) injection is being investigated for HIV preexposure prophylaxis due to its potent antiretroviral activity and infrequent dosing requirement. A subset of healthy adult volunteers participating in a Phase I study assessing cabotegravir tissue pharmacokinetics underwent serial magnetic resonance imaging (MRI) assess drug depot localization kinetics following single LA IM targeted injection. Methods Eight participants (four men, four women)...