
Andrew RowlandFlinders University · Department of Clinical Pharmacology
Andrew Rowland
PhD (pharmacology)
About
170
Publications
32,650
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Introduction
As the leader of the Flinders University Precision Medicine Group Liver EV Biomarker Discovery Team, my research focus is the translation of precision medicine approaches to support direct improvements for cancer patients by facilitating the maximal therapeutic benefit from targeted anti-cancer medicines, while minimizing the harmful effects of these drugs.
Additional affiliations
January 2010 - March 2020
Education
March 2005 - November 2009
February 2001 - November 2004
Publications
Publications (170)
Aims
Demonstrate the presence of cytochrome P450 (CYP) and UDP‐glucuronosyltransferase (UGT) proteins and mRNAs in isolated human plasma exosomes and evaluate the capacity for exosome‐derived biomarkers to characterize variability in CYP3A4 activity.
Methods
The presence of CYP and UGT protein and mRNA in exosomes isolated from human plasma and He...
It is now established that a drug's pharmacokinetics‐absorption‐distribution‐metabolism‐excretion‐drug‐drug interaction (PK‐ADME‐DDI) profile can be modulated by age, disease, and genotype. In order to facilitate subject phenotyping and clinical DDI assessment, therefore, various endogenous compounds (in plasma and urine) have been pursued as drug‐...
Cytochrome P450 3A4 (CYP3A4) catalyses the metabolism of > 30% of clinically used small molecule drugs. Induction of CYP3A4 is often associated with clinically important metabolic drug–drug interactions (DDIs). To collate published data regarding induction of CYP3A4 expression by rifampin and identify an optimal protocol to study DDIs using physiol...
Small extracellular vesicles (sEV) have emerged as a potential rich source of biomarkers in human blood and present the intriguing potential for a ‘liquid biopsy’ to track disease and the effectiveness of interventions. Recently, we have further demonstrated the potential for EV derived biomarkers to account for variability in drug exposure. This s...
Tumour mutational burden (TMB) is an established biomarker for patients treated with immune checkpoint inhibitors (ICIs). The optimal TMB cut-off is uncertain. It is also uncertain whether there is a sharp TMB threshold or a more graduated change in clinical outcomes as TMB increases.
We aimed to determine the relationship between TMB and ICI treat...
Intravenous midazolam is frequently used for procedural sedation. Use of ritonavir containing antivirals in patients requiring procedural sedation with intravenous midazolam is postulated to increase the risk or prolong the consequences of exposure related adverse events. The primary objective of this study was to characterize interaction of ritona...
Importance
With the growing use of large language models (LLMs) in education and health care settings, it is important to ensure that the information they generate is diverse and equitable, to avoid reinforcing or creating stereotypes that may influence the aspirations of upcoming generations.
Objective
To evaluate the gender representation of LLM...
Aims
Drug exposure and response is determined by pharmacokinetic (PK) and pharmacodynamic (PD) profiles. Interindividual differences in abundance of drug metabolizing enzymes (DMEs) and drug target proteins underpin PK and PD variability and impact treatment efficacy and tolerability. Extracellular vesicles (EVs) carry protein cargo inherited from...
Unlocking the full potential of clinical trials through comprehensive CSR and IPD sharing can revolutionize cancer care, enhance safety evaluations, and reduce bias in systematic reviews. It is time for all stakeholders to embrace transparency and advance patient-centered outcomes.
Background
Multiple studies have indicated that patients with high body mass index (BMI) may have favourable survival outcomes following treatment with an immune checkpoint inhibitor (ICI). However, this evidence is limited by several factors, notably the minimal evidence from randomised controlled trials (RCTs), the use of categorised BMI with inc...
Objectives
To evaluate the effectiveness of safeguards to prevent large language models (LLMs) from being misused to generate health disinformation, and to evaluate the transparency of artificial intelligence (AI) developers regarding their risk mitigation processes against observed vulnerabilities.
Design
Repeated cross sectional analysis.
Setti...
Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their
cell of origin and change the functions and phenotypes of other cells. These features
indicate strong biomarker and therapeutic potential and have generated broad interest,
as evidenced by the steady year-on-year increase in the numbers of scientific publicati...
PF‐06835919, a ketohexokinase inhibitor, presented as an inducer of cytochrome P450 3A4 (CYP3A4) in vitro (human primary hepatocytes), and static mechanistic modeling exercises predicted significant induction in vivo (oral midazolam area under the plasma concentration‐time curve [AUC] ratio [AUCR] = 0.23–0.79). Therefore, a drug–drug interaction st...
Advances in technologies to isolate extracellular vesicles (EVs) and detect/quantify their cargo underpin the novel potential of these circulating particles as a liquid biopsy to understand physiology and disease. One organ of particular interest in terms of utilizing EVs as a liquid biopsy is the liver. The extent to which EVs originating from the...
Data sharing is essential for promoting scientific discoveries and informed decision-making in clinical practice. In 2013, PhRMA/EFPIA recognised the importance of data sharing and supported initiatives to enhance clinical trial data transparency and promote scientific advancements. However, despite these commitments, recent investigations indicate...
Importance
The pharmaceutical industry has made substantial investments in developing processes for sharing individual-participant data (IPD) from clinical trials. However, the utility and completeness of shared IPD and supporting documents must be evaluated to ensure the potential for scientific advancements from the data sharing ecosystem can be...
530
Background: Patient-reported outcomes (PROs) are captured in validated tools to provide the patients’ perspective and voice on their physical, social, emotional, functional, and cognitive abilities. Pre-treatment PROs have shown prognostic importance in other cancer types, however, the prognostic value of PROs in breast cancer has been minimall...
Drug-drug interactions (DDIs) arising from the perturbation of drug metabolising enzyme activities represent both a clinical problem and a potential economic loss for the pharmaceutical industry. DDIs involving glucuronidated drugs have historically attracted little attention and there is a perception that interactions are of minor clinical relevan...
Background:
Epirubicin is an anthracycline antineoplastic drug that is primarily used in combination therapies for the treatment of breast, gastric, lung and ovarian cancers and lymphomas. Epirubicin is administered intravenously (IV) over 3 to 5 min once every 21 days with dosing based on body surface area (BSA; mg/m2). Despite accounting for BSA...
Extracellular vesicles (EVs) are naturally occurring membranous particles that can be isolated from blood and other biofluids. EVs have drawn considerable attention for their potential as a minimally invasive biomarker source for a range of conditions, based on tissue-specific expression of proteins and other molecular information. To promote robus...
Purpose:
The introduction of COVID-19 therapies containing ritonavir has markedly expanded the scope of use for this medicine. As a strong cytochrome P450 3A4 inhibitor, the use of ritonavir is associated with a high drug interaction risk. There are currently no data to inform clinician regarding the likely magnitude and duration of interaction be...
If you are worried that studying pharmacology will be difficult to apply to clinical practice, Pharmacology for Health Professionals is the book for you. Written by experienced health professional educators, this textbook brings the study of drugs and medicines to life.
This title is considered the most authoritative text in Australia and New Zeal...
Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease, with an estimated prevalence of between 20 and 30% worldwide. Observational data supported by in vitro and pre-clinical animal models of MAFLD suggest meaningful differences in drug disposition in MAFLD patients. This study aimed to build a physiologically ba...
Extracellular vesicles (EVs) are membrane‐bound nanosized particles released by cells into bodily fluids containing an array of molecular cargo. Several characteristics, including stability and accessibility in biofluids such as blood and urine, make EVs and associated cargo attractive biomarkers and therapeutic tools. To promote robust characteris...
Background
Immune checkpoint inhibitors (ICIs) is the main treatment option for patients with metastatic renal cell carcinoma (mRCC); however, significant heterogeneity in response is commonly observed. This study aimed to evaluate the ability of C-reactive protein (CRP) to predict overall survival (OS) and progression-free survival (PFS) in patien...
Importance:
Emerging policies drafted by the pharmaceutical industry indicate that they will transparently share clinical trial data. These data offer an unparalleled opportunity to advance evidence-based medicine and support decision-making.
Objective:
To evaluate the eligibility of independent, qualified researchers to access individual partic...
Chronic liver diseases represent a burgeoning health problem affecting billions of people worldwide. The insufficient performance of current minimally invasive tools is recognised as a significant barrier to the clinical management of these conditions. Extracellular vesicles (EVs) have emerged as a rich source of circulating biomarkers closely link...
Introduction
Gut dysbiosis may reduce immune checkpoint inhibitor (ICI) efficacy. Antibiotics and proton pump inhibitors (PPIs) are commonly used drugs causing gut dysbiosis. There is limited randomised controlled trial (RCT) evidence on whether antibiotics or PPIs impact ICI benefit versus comparator treatments.
Methods
This study pooled five RCT...
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Definitive diagnosis of the progressive form, non-alcoholic steatohepatitis (NASH), requires liver biopsy, which is highly invasive and unsuited to early disease or tracking changes. Inadequate performance of current minimally invasive tools is a critical barrier to...
Background: Clozapine is a key antipsychotic drug for treatment-resistant schizophrenia but exhibits highly variable pharmacokinetics and a propensity for serious adverse effects. Currently, these challenges are addressed using therapeutic drug monitoring (TDM). This study primarily sought to (i) verify the importance of covariates identified in a...
Introduction:
The discrimination performance of Bellmunt risk score for immune checkpoint inhibitor (ICI) therapy is largely unknown. This study aimed to validate and enhance discrimination of the Bellmunt score in patients with urothelial carcinoma treated with ICIs.
Patients and methods:
Cox proportional hazard analysis were used to validate o...
The inhibitory effects of fifteen NSAIDs from six structurally distinct classes on human liver microsomal morphine glucuronidation were investigated. Ki values of selected NSAIDs were generated and employed to assess DDI liability in vivo. Potent inhibition was observed for mefenamic acid and tolfenamic acid; respective IC50 values for morphine 3-...
Preparations of plasma‐derived small extracellular vesicles (sEV) were deployed as liquid biopsy to study cytochrome P450 (CYP) 3A4 (CYP3A4) induction following modafinil (MOD) 400 mg once daily x 14 days (young healthy volunteers, N = 10 subjects). Induction was confirmed using the 4β‐hydroxycholesterol‐to‐cholesterol (4βHC/C) ratio, a plasma CYP3...
Proton pump inhibitors (PPIs) are commonly used concomitant to cancer treatment and they induce gut microbiota changes. It is increasingly apparent that gut dysbiosis can reduce the effectiveness of immune checkpoint inhibitors (ICI). However, little is known about PPI effects on outcomes with ICIs, particularly in combination, ICI approaches.
Post...
Drug-drug interaction (DDI) studies are mandated in drug development; however, protocols for evaluating the impact of cytochrome P450 (CYP) inhibition on new molecular entities are currently inconsistent. This study utilised validated physiologically based pharmacokinetic (PBPK) software to define the optimal dose, frequency, and duration of clarit...
Extracellular vesicles (EVs) are small, non-replicating, lipid encapsulated particles that contain a myriad of protein and nucleic acid cargo derived from their tissue of origin. The potential role of EV derived biomarkers to the study of drug metabolism and disposition (DMD) has gained attention in recent years. The key trait that makes EVs an att...
We thank Auclin et al. [...]
Introduction: Orally administered small molecule kinase inhibitors (KI) are a key class of targeted anti-cancer medicines that have contributed substantially to improved survival outcomes in patients with advanced disease. Since the introduction of KIs in 2001, there has been a building body of evidence that the benefit derived from these drugs may...
Introduction:
Afatinib is a first-line treatment option for patients with an advanced nonsmall cell lung cancer (NSCLC) expressing an epidermal growth factor receptor (EGFR) activating mutation. This study aimed to evaluate the association between early adverse events induced by afatinib and overall survival (OS) and progression free survival (PFS...
Background:
Abemaciclib is a CDK4/6 inhibitor used to treat hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+, HER2-) advanced breast cancer (ABC). The prognostic value of patient-reported outcomes (PROs) have been minimally explored for treatment outcomes with CDK4/6 inhibitors. The performance of PROs compared to...
Vemurafenib, a BRAF inhibitor, is commonly used in combination of cobimetinib for the treatment of melanoma. In the current study, we evaluated the relationship between vemurafenib exposure, as measured by the estimated apparent clearance (CLB ) at steady state and any grade ≥ 3 toxicity, grade ≥ 3 skin rash or toxicity requiring dose modification...
Machine learning (ML) may enhance the efficiency of developing accurate prediction models for survival, which is critical in informing disease prognosis and care planning. This study aimed to develop an ML prediction model for survival outcomes in patients with urothelial cancer-initiating atezolizumab and to compare model performances when built u...
The primary objective of this study is to evaluate the capacity of concentration-guided sorafenib dosing protocols to increase the proportion of patients that achieve a sorafenib maximal concentration (Cmax) within the range 4.78 to 5.78 μg/mL. A full physiologically based pharmacokinetic model was built and validated using Simcyp® (version 19.1)....
Liver‐derived small extracellular vesicles (sEV), prepared from small sets of banked serum samples using a novel two‐step protocol, were deployed as liquid biopsy to study the induction of cytochromes P450 (CYP3A4, CYP3A5, CYP2D6) and organic anion transporting polypeptides (OATP1B1 and OATP1B3) during pregnancy (non‐pregnant [T0], 1st, 2nd and 3rd...
This letter to the editor highlights additional analyses to add to the recently reported study by Rugo et al., regarding abemaciclib treatment for HR+/HER2− breast cancer.
Introduction
Neutropenia and diarrhoea are common and potentially serious adverse events associated with abemaciclib in advanced breast cancer (ABC), and the risk factors have been minimally explored. The study aimed to develop clinical prediction tools that allow personalized predictions of neutropenia and diarrhoea following abemaciclib initiatio...
The lung immune prognostic index (LIPI) is proposed to differentiate prognosis and treatment benefit from immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC). There is minimal information on the predictive importance with first-line, combination ICI approaches. In post-hoc analysis of IMpower150, Cox-proportional haza...
While many studies have evaluated the relationship between BMI and breast cancer outcomes, it is unclear whether this relationship is consistent between early breast cancer (BC) and advanced BC. The study included 5099 patients with HER2 positive early BC (EBC) and 3496 with HER2 positive advanced BC (ABC). In the EBC cohort, higher BMI was associa...
Objectives:
Antihypertensives and cancer have a complex relationship. Among the antihypertensives, renin--angiotensin system inhibitors have strong immune modulatory activities that may affect immune check point inhibitors-related outcomes in cancer patients. We evaluated the association between concomitant use of renin--angiotensin system inhibit...
Guidance regarding the effect of codeine and its metabolites on foetal development is limited by small studies and inconsistent findings. The primary objective was to use physiologically based pharmacokinetic modelling to investigate the impact of gestational stage and maternal CYP2D6 phenotype on foetal morphine exposure following codeine administ...
PurposeSorafenib is an oral tyrosine kinase inhibitor (TKI) and first-line treatment option for advanced hepatocellular carcinoma (HCC). Preliminary evidence indicates proton pump inhibitors (PPI) may affect the absorption of TKIs through decreased gut dissolution. This study aims to evaluate the impact of PPI use on the survival outcomes of advanc...
Enzymes of the UDP-glucuronosyltransferase (UGT) superfamily contribute to the elimination of drugs from almost all therapeutic classes. Awareness of the importance of glucuronidation as a drug clearance mechanism along with increased knowledge of the enzymology of drug and chemical metabolism has stimulated interest in the development and applicat...
Purpose:
Emerging evidence indicates that gut microbiota dysbiosis can reduce the effectiveness of immune checkpoint inhibitors (ICI). Proton pump inhibitors (PPI) are known to induce gut microbiota changes. However, little is known on the effects of PPIs on outcomes with ICI therapy, and it has not been explored in urothelial cancer treatment.
E...
Background:
Immune-related adverse events (irAEs) are known to occur in patients with cancer who are treated with immune checkpoint inhibitors. However, limited literature exists on the incidence, time of onset, and risk factors for irAEs, particularly those affecting multiple organs, associated with anti-PD-L1 inhibitors.
Methods:
A post hoc po...
Background
Retinopathy is a common adverse event with mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors. Little is known about the pathophysiology of MEK inhibitor-associated retinopathy (MEKAR). Since MEKAR has many similarities to central serous chorioretinopathy (CSCR), they may share common risk factors. The aim of this s...
Introduction: Beta-blockers (BB) are commonly used to manage cardiovascular disease and may have benefits in controlling complications of anti-HER2 therapies. This study aimed to evaluate the association of pre-existing BB use with survival outcomes in patients initiating anti-HER2 therapy for advanced breast cancer (ABC).
Materials and Methods: Da...
Selecting the dose of a targeted cancer medicine that is most appropriate for a specific individual is a rational approach to maximize therapeutic outcomes and minimize toxicity. There are many different options for optimizing the dose of targeted cancer medicines and the purpose of this review is to provide a comprehensive comparison of the main o...
Antibiotic effects on the gut microbiota may negatively impact survival with immune checkpoint inhibitors (ICIs). However, there is minimal evidence regarding whether antibiotic impacts are specific to ICIs or impacts in urothelial carcinoma (UC). In a post hoc analysis of IMvigor210 (single-arm atezolizumab) and IMvigor211 (phase III randomised tr...
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, affecting approximately one-third of the global population. Most affected individuals experience only simple steatosis-an accumulation of fat in the liver-but a proportion of these patients will progress to the more severe form of the disease, non-alcoholic steatohe...
There has been minimal research on the prognostic value of patient‐reported outcomes (PROs) for immune checkpoint inhibitors (ICIs). The relative performance of PROs compared to established markers such as Eastern Cooperative Oncology Group Performance Status (ECOG‐PS) and the Lung Immune Prognostic Index (LIPI) is unknown. In our study, data from...
Background
Preliminary evidence indicates that early tumor shrinkage (ETS) following immune checkpoint inhibitor (ICI) initiation may be associated with survival outcomes in patients with advanced melanoma. ETS has not been explored as a biomarker of survival outcomes or patient-reported outcomes in patients with advanced non-small cell lung cancer...
Background
Sorafenib is a current first-line treatment option for advanced hepatocellular carcinoma (HCC). This study aimed to evaluate the impact of early adverse events (AEs) requiring sorafenib dose adjustment on survival outcomes of patients with advanced HCC.Methods
The study was a secondary analysis of the phase III clinical trial NCT00699374...
Background: This study aimed to investigate the impact of early adverse events (AE) following the initiation of lapatinib plus capecitabine on the progression-free survival (PFS) and overall survival (OS) outcomes of human epidermal growth factor receptor 2 (HER2) positive advanced breast cancer (ABC) patients.
Methods: A secondary analysis of part...
Background:
Rash is one of the most common severe adverse events associated with use of vemurafenib for the treatment of melanoma, either as monotherapy or in combination with cobimetinib. The study aimed to identify pre-treatment patient characteristics predictive of developing severe rash with vemurafenib therapy.
Methods:
This was a secondary...
Purpose:
Immune checkpoint inhibitors (ICI) are a significant advance to the treatment of advanced non-small cell lung cancer (NSCLC), however, their initiation is associated with heterogeneity in outcomes. This study aimed to develop and validate a prognostic tool of survival in advanced NSCLC patients treated with ICIs.
Experimental design:
A...
Despite advances in the breast cancer treatment, significant variability in patient outcomes remain. This results in significant stress to patients and clinicians. Treatment-specific clinical prediction models allow patients to be matched against historical outcomes of patients with similar characteristics; thereby reducing uncertainty by providing...
Within the drug pharmacokinetics (PK)-absorption, distribution, metabolism, and excretion (ADME) research community, investigators regularly generate in vitro data sets using appropriately vendor-sourced and processed human tissue. Such data enable drug screening, the generation of kinetic parameters, extrapolation of in vitro to in vivo, as well a...