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 HepaRG cell culture medium was determined by mass spectrometry and reverse transcription–polymerase chain reaction, respectively. The concordance between exosome‐derived CYP3A4 biomarkers and midazolam apparent oral clearance (CL/F) was evaluated in a small proof‐of‐concept study involving six genotyped (CYP3A4 *1/*1 and CYP3A5 *3/*3) Caucasian males.Results: Exosomes isolated from human plasma contained peptides and mRNA originating from CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 2 J2, 3A4 and 3A5, UGT 1A1, 1A3, 1A4, 1A6, 1A9, 2B4, 2B7, 2B10 and 2B15, and NADPH‐cytochrome P450 reductase. Mean (95% confidence interval) exosome‐derived CYP3A4 protein expression pre‐ and post‐rifampicin dosing was 0.24 (0.2–0.28) and 0.42 (0.21–0.65) ng ml^–1 exosome concentrate. Mean (95% confidence interval) exosome CYP3A4 mRNA expression pre‐ and post‐rifampicin dosing was 6.0 (1.1–32.7) and 48.3 (11.3–104) × 10^–11 2^‐ΔΔCt, respectively. R² values for correlations of exosome‐derived CYP3A4 protein expression, CYP3A4 mRNA expression, and ex vivo CYP3A4 activity with midazolam CL/F were 0.905, 0.787 and 0.832, respectively.Conclusions: Consistent strong concordance was observed between exosome‐derived CYP3A4 biomarkers and midazolam CL/F. The significance of these results is that CYP3A4 is the drug‐metabolizing enzyme of greatest clinical importance and variability in CYP3A4 activity is poorly described by existing precision dosing strategies.

Recent advancements in large language models (LLMs) enable real-time web search, improved referencing, and multilingual support, yet ensuring they provide safe health information remains crucial. This perspective evaluates seven publicly accessible LLMs-ChatGPT, Co-Pilot, Gemini, MetaAI, Claude, Grok, Perplexity-on three simple cancer-related queries across eight languages (336 responses: English, French, Chinese, Thai, Hindi, Nepali, Vietnamese, and Arabic). None of the 42 English responses contained clinically meaningful hallucinations, whereas 7 of 294 non-English responses did. 48 % (162/336) of responses included valid references, but 39 % of the English references were.com links reflecting quality concerns. English responses frequently exceeded an eighth-grade level, and many non-English outputs were also complex. These findings reflect substantial progress over the past 2-years but reveal persistent gaps in multilingual accuracy, reliable reference inclusion, referral practices, and readability. Ongoing benchmarking is essential to ensure LLMs safely support global health information dichotomy and meet online information standards.

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 (C_max) 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). The model was used to simulate sorafenib exposure in 1000 Sim-Cancer subjects over 14 days. The capacity of concentration-guided sorafenib dose adjustment, with/without model-informed dose selection (MIDS), to achieve a sorafenib C_max within the range 4.78 to 5.78 μg/mL was evaluated in 500 Sim-Cancer subjects. A multivariable linear regression model incorporating hepatic cytochrome P450 (CYP) 3A4 abundance, albumin concentration, body mass index, body surface area, sex and weight provided robust prediction of steady-state sorafenib C_max (R² = 0.883; p < 0.001). These covariates identified subjects at risk of failing to achieve a sorafenib C_max ≥ 4.78 μg/mL with 95.0% specificity and 95.2% sensitivity. Concentration-guided sorafenib dosing with MIDS achieved a sorafenib C_max within the range 4.78 to 5.78 μg/mL for 38 of 52 patients who failed to achieve a C_max ≥ 4.78 μg/mL with standard dosing. In a simulation setting, concentration-guided dosing with MIDS was the quickest and most effective approach to achieve a sorafenib C_max within a designated range.

Background: ChatGPT has recently emerged as a disruptive technology, potentially impacting various societal dimensions, including pharmacy practices. In Thailand, community pharmacists are navigating transitions as patients increasingly rely on digital tools for healthcare recommendations. This study explores the attitudes of community pharmacists in Hatyai, one of Thailand's most populated cities, towards the integration of ChatGPT in pharmacy services. Method: ChatGPT-3.5 was used to generate responses to three questions concerning the use of medicine in special populations in the Thai language. These responses were then incorporated into a questionnaire and evaluated using a Likert scale from 1 to 5. Participants who consented were asked to rate the responses and participate in an in-depth interview. Results: The majority of participants rated the responses favorably, with scores of 4 and 5 accounting for at least 60% of the ratings. Only a small proportion of responses received doubtful ratings (score of 3) or was in disagreement, ranging from 20% to 40%. Moreover, open opinions extracted from the interviews suggested that participants viewed ChatGPT as a capable assistant, as it provided fast yet reasonably accurate information in the Thai language. Conclusion: The findings indicate that community pharmacists view ChatGPT as a capable assistant, albeit noting the need for further refinements. The study underscores the importance for pharmacists to proactively adapt to technological advancements, particularly those affecting patient safety, to enhance healthcare delivery and optimize treatment outcomes.