Wiley: Basic & Clinical Pharmacology & Toxicology: Table of Contents

Detection of Anti‐Infliximab and Anti‐Adalimumab Antibodies Below Manufacture's Threshold in a TDM Cohort Using Signal‐to‐Noise Ratio

Lise Pedersen — Mon, 08 Jun 2026 23:55:07 -0700

Basic &Clinical Pharmacology &Toxicology, Volume 139, Issue 1, July 2026.

Correction to “6‐Nitrodopamine Potentiates Catecholamine‐Induced Ca2+i Release in Human Aortic Smooth Muscle and Modulates Vascular Smooth Muscle Contractility”

Fri, 05 Jun 2026 03:54:51 -0700

Basic &Clinical Pharmacology &Toxicology, Volume 139, Issue 1, July 2026.

Prescribing Patterns in Fatal Intoxications Involving Zopiclone and Alprazolam: An Observational Register‐Based Study

Wed, 03 Jun 2026 22:09:30 -0700

ABSTRACT

Background

Zopiclone was recently identified as a frequent contributor to fatal drug-intoxications in Sweden. However, characteristics of misuse and factors associated with prescribed use remain insufficiently described. Alprazolam has a more established misuse profile.

Objective

The aim of the study was to describe and compare characteristics of fatal intoxications positive for zopiclone or alprazolam, focusing on prescription status and factors associated with prescribed drug use.

Methods

Fatal intoxications between 2012 and 2020 with zopiclone and/or alprazolam in blood were identified using the Swedish Cause of Death Register and the Swedish forensic medicine database. Prescriptions within 1 year before death, and health and sociodemographic data were obtained from national registers.

Results

Among 1270 zopiclone cases, 84% were prescribed users compared to 22% of 1532 alprazolam cases. For both substances, prescribed use was associated with female sex (zopiclone: aOR = 1.68, 95% CI = 1.22–2.30; alprazolam: aOR = 2.04, 95% CI = 1.54–2.71), suicide relative to accidental intoxication (zopiclone: aOR = 1.61, 95% CI = 1.11–2.33; alprazolam: aOR = 3.21, 95% CI = 2.16–4.75) and age ≥ 46 years (zopiclone: aOR = 2.26, 95% CI = 1.45–3.54; alprazolam: aOR = 3.20, 95% CI = 2.29–4.46). Psychiatry-contact and previous self-harm were associated with prescribed zopiclone use, but not alprazolam.

Conclusion

Fatal intoxications involving zopiclone differ from alprazolam. While factors associated with prescribed use were often shared, substance-specific preventative strategies could be beneficial.

Efficacy and Safety of the Traditional Chinese Medicine Yunnan Baiyao in the Treatment of Diabetic Foot Ulcers: a Multicentre, Randomised Clinical Trial

Wed, 03 Jun 2026 18:47:48 -0700

ABSTRACT

Diabetic foot ulcers (DFUs) constitute an increasing clinical challenge, driven by the escalating prevalence of diabetes and the paucity of effective therapies. This multicentre, randomised, open-label, blinded-endpoint trial investigated the efficacy and safety of Yunnan Baiyao (YNBY), a traditional Chinese medicine, as an adjunctive therapy for DFUs. Patients with DFUs (Wagner Grade 3 or 4) from three hospitals were randomised 2:2:1 to YNBY powder, YNBY ointment and control groups, all receiving standard of care. A total of 117 patients completed the trial. The 2-week percentage of wound area reduction (PWAR) was significantly higher in YNBY powder (61.5%) and YNBY ointment (70.0%) groups than that in the control group (46.4%, p < 0.01). The 1-week PWAR was almost doubled in the YNBY powder group (36.1%) and the YNBY ointment group (42.9%) relative to the control group (19.5%, p < 0.05). The percentage of complete healing within 8 weeks (control group, 25.0%; powder group, 54.2%; ointment group, 61.9%) did not reach statistical significance. No significant differences were observed between the YNBY powder and ointment groups. The adjunctive use of YNBY powder or ointment with standard therapy significantly accelerates wound closure. This effective, inexpensive, easy-to-apply traditional medicine can serve as an effective adjunct to standard DFUs care.

Trial registration: https://clinicaltrials.gov/, NCT06197412 (Registration Date: 12/17/2023)

Quantifying the Impact of Discrepancies Between Actual and Recorded Blood Sampling Times on Bayesian Forecasting for Area Under the Concentration–Time Curve Estimation of Vancomycin

Wed, 03 Jun 2026 17:08:32 -0700

ABSTRACT

The effect of discrepancies in sampling time on the accuracy of area under the concentration–time curve (AUC) estimation remains unclear. We evaluated how discrepancies between actual and recorded blood sampling times impact vancomycin AUC estimation using one-point (trough) and two-point (trough and peak) strategies in critically ill patients. In total, 25 patients at five Japanese hospitals were enrolled; 21 underwent sampling on Day 1 (AUC_day1) and 14 on Days 3–5 (AUC_ss). Reference AUCs were calculated using trapezoidal methods. Bayesian forecasting estimated AUCs from one- or two-point sampling. Systematic trough (≤ 4 h earlier) and peak (−1 to +4 h) time discrepancies were introduced. Predictive performance was defined as estimated/reference AUC ratios within an acceptable range of 0.9–1.1. For AUC_day1, two-point sampling was more robust to trough discrepancies than one-point sampling (acceptable interquartile range [IQR] up to 105 vs. 30 min) but highly sensitive to peak timing (acceptable IQR −20 and +10 min). For AUC_ss, similar trends were observed. Overall, two-point sampling offers superior robustness against trough discrepancies. However, because peak sampling is highly sensitive to timing errors, if the exact peak sampling time cannot be verified, clinicians may consider remeasuring the concentration or switching to one-point trough sampling.

Astragaloside IV Ameliorates Allergic Rhinitis Comorbid With Asthma by Inhibiting the Antigen‐Presenting Function of B Cells

Wed, 03 Jun 2026 02:59:51 -0700

ABSTRACT

Astragaloside IV (AST) is one of the main active components of Astragalus membranaceus (Fisch.) Bunge, possessing definite immunomodulatory properties. However, its efficacy and mechanism remain unclear in allergic rhinitis comorbid with asthma (ARCA). This study aims to investigate whether AST can improve ARCA by inhibiting antigen presentation. An ARCA mouse model was established to assess airway allergic symptoms; serum inflammatory factors were detected by ELISA, airway tissue pathology by HE, PAS and Masson staining and inflammatory factor expression, antigen-presenting cell activation and JAK2/STAT1 pathway activity by WB, IHC and IF. AST improved airway allergic symptoms, downregulated the expression of OVA-sIgE and IL-4 and upregulated the expression of OVA-sIgG. It also alleviated eosinophil infiltration, goblet cell metaplasia and collagen fibre proliferation and inhibited the expression of ECP, CD3e, CD4 and IL-4 in airway tissues. The antigen-presenting function of B cells in the airway tissues of ARCA mice was activated, while AST inhibited this function. Moreover, AST downregulated the expression of p-JAK2, STAT1, p-STAT1 and MHC II in airway tissues. In conclusion, B cells are the key effector cells mediating antigen presentation in the challenge phase of ARCA. AST can inhibit the antigen-presenting function of B cells via regulating the JAK2/STAT1 signalling pathway, thereby alleviating the Th2-type inflammatory response in ARCA.

Genomic and Sex Contributions to Interindividual Variability in Pitavastatin Bioavailability

Fri, 29 May 2026 02:46:02 -0700

ABSTRACT

Aim

This study investigates pharmacogenetic determinants of pitavastatin disposition using a candidate-gene approach.

Methods

In 48 healthy volunteers, 138 variants across 40 genes involved in drug metabolism and transport were analysed to assess their relationship with pitavastatin pharmacokinetics, alongside the influence of sex and biogeographical origin.

Results

Women exhibited 35% higher AUC and C _max values than men; however, these differences disappeared after adjusting for the dose/weight (DW) ratio, with only a 22% increase in t _1/2 remaining. The most prominent finding was the 50%–65% increase in AUC/DW and C _max/DW observed in decreased function (DF) individuals compared with increased function (IF) and normal function (NF) carriers of SLCO1B1 phenotype, reinforcing its role as the primary hepatic uptake transporter for pitavastatin. Additional variants in efflux transporters such as ABCB1, ABCC3 and ABCG2 may also contribute to interindividual variability, albeit to a lesser extent. Among drug-metabolising enzymes, CYP4F2 emerged as a candidate for further investigation, given the 36% reduction in AUC_48h/DW associated with the rs3093200 variant. No significant associations were detected for CYP2D6 or CYP2C9 genes. Evidence to date does not indicate a meaningful impact of UGT enzymes on pitavastatin pharmacokinetics.

Conclusion

Overall, these findings highlight several genetic factors that may modulate pitavastatin disposition, warranting confirmation through functional studies or larger population cohorts.

Evidence for a Two‐Step Model for Activation of GPR25 by the Chemoattractant CXCL17

Wuqing Yang, Sean P. Giblin, James E. Pease — Thu, 28 May 2026 07:22:55 -0700

ABSTRACT

CXCL17 was recently reported to activate GPR25, a receptor expressed by T-regulatory cells. Although classified as a chemokine, the activity of CXCL17 is ablated by minor C-terminal truncation, suggesting a novel mode of receptor activation. We set out to test this hypothesis by mutagenesis. GPR25 was expressed in the murine pre-B cell line L1.2 and mediated robust migration of transfectants to nanomolar concentrations of recombinant CXCL17 (24–119). The N-terminally truncated form of CXCL17 (64–119) was also chemotactic for GPR25 transfectants, albeit with severely reduced potency. Modelling of CXCL17:GPR25 implied multiple interactions between the N- and C-termini of CXCL17 with GPR25, which was validated by mutagenesis. Cells expressing a chimeric FPR1:GPR25 construct responded chemotactically to CXCL17 but with significantly reduced potency compared with wild-type GPR25 transfectants, implicating the GPR25 N-terminus in CXCL17 recognition. Mutagensis of the GPR25 residues W95, R178 and R264 resulted in a complete loss of chemotactic responsiveness to CXCL17, consistent with the residues interacting with the C-terminal CXCL17 motif. In conclusion, we verify GPR25 as a bona fide CXCL17 receptor and suggest a two-step model of GPR25 activation, in which the receptor N-terminus orients CXCL17 for activation of GPR25 via its C-terminus. We also advocate the reclassification of CXCL17 as a chemoattractant distinct from the chemokine family.

Transient Receptor Potential Channels in Modulating Synaptic Plasticity and Cognitive Function: Potential Role of Pharmacological Agents

Thu, 28 May 2026 06:11:16 -0700

ABSTRACT

Cognitive impairment represents the most prevalent complication of neurological diseases (NDs), which significantly affects the quality of life in affected patients. Current treatments primarily target neurotransmitter imbalances but do not act on the key pathological events such as Ca²⁺ dyshomeostasis, oxidative stress, microglia activation, mitochondrial dysfunction and neuroinflammation that occur in the brain of patients with NDs. Therefore, existing treatments fail to stop the progressive cognitive decline in these diseases. Thus, there is a critical need for literature which covers the potential novel therapeutic targets along with their modulators for the effective treatment of cognitive impairment associated with NDs. Recently, transient receptor potential (TRP) channels have emerged as key regulators of these pathological events implicated in ND-associated cognitive impairment. Many preclinical studies have demonstrated that pharmacological modulation of specific TRP channels can improve cognitive function in animal models of NDs. However, clinical translation of TRP channel modulators is still constrained due to a lack of subtype specificity, limited clinical data and difficulties in drug delivery across the blood–brain barrier (BBB). In the present review, we have discussed the structural diversity of TRP channels, their role in regulating synaptic plasticity and cognitive function, and their potential as pharmacological targets for the treatment of cognitive impairment, which can provide a direction for future research in this field.

Xiao‐Jie‐An Capsule Attenuates Oestrogen‐ and Progestogen‐Induced Mammary Gland Hyperplasia by Modulating Sex Hormone Levels and Reducing Inflammatory Response

Sun, 24 May 2026 21:14:55 -0700

Xiao-Jie-An capsule, a traditional Chinese medicine formula, effectively attenuates oestrogen- and progestogen-induced mammary gland hyperplasia in rats. Mechanistically, Xiao-Jie-An capsule attenuates mammary gland hyperplasia through inhibiting mammary epithelial cell proliferation, promoting mammary epithelial cell apoptosis, regulating endocrine function and reducing inflammatory responses.

ABSTRACT

Xiao-Jie-An capsule (XJA), a traditional Chinese medicine formulation consisting of six herbal components, has been used to treat MGH for a long time. Aim of this study was to determine the therapeutical impact of XJA on an MGH rat model and the underlying mechanism. The MGH model was established by daily intramuscular injections of estradiol benzoate (0.5 mg/kg) for 25 days, then progesterone (5 mg/kg) for 5 days. Network pharmacological analysis and molecular biological assays were conducted to determine the pharmacological targets of XJA. XJA significantly reduced nipple height and diameter and effectively suppressed histopathological hallmarks of MGH. Additionally, XJA markedly decreased the expression of Ki67 and the expression of proliferating cell nuclear antigen, increased the terminal deoxynucleotidyl transferase dUTP nick-end labelling and lowered the Bcl-2/Bax ratio in mammary tissue of MGH rats. Furthermore, XJA modulated endocrine disorder by reducing blood follicle–stimulating hormone and estradiol (E2), while increasing luteinising hormone and androgen concentrations. Concomitant anti-inflammatory effects were found by decreased pro-inflammatory cytokines IL-1β, IL-2, IL-6 and TNF-α; inhibited TLR4 expression and attenuated NF-κB phosphorylation. Our experimental results suggest that XJA effectively mitigated oestrogen- and progesterone-induced MGH by modulating sex hormone levels and reducing inflammatory response.

Levothyroxine Treatment During Pregnancy: A Metabolomics Study

Olli Kärkkäinen, Heidi Sahlman, Leea Keski‐Nisula, Jaana Rysä — Fri, 22 May 2026 06:15:32 -0700

ABSTRACT

Levothyroxine is one of the most prescribed drugs during pregnancy. Our aim was to determine levothyroxine treatment-associated changes in the metabolite profiles and link these to the health of the newborn. Metabolite profiles of 118 levothyroxine-treated and 118 healthy control pregnancies were determined with nuclear magnetic resonance-based metabolomics from (1) umbilical cord blood samples, (2) samples collected during the first trimester and (3) during delivery from the pregnant women. There was a modest negative correlation between cord blood thyroid stimulating hormone (CBTSH) concentrations and Apgar scores at the 1 and 5 min time points in levothyroxine-treated pregnancies. Furthermore, the concentrations of cord serum metabolites linked with anaerobic glycolysis, for example, lactate, citrate and glycerol, as well as all measured amino acids were negatively associated with Apgar scores. Moreover, cord serum concentrations of lactate, glycerol and alanine were modestly correlated with CBTSH concentrations in the levothyroxine-treated pregnancies. In the during delivery samples, there was small but significant decrease in cholesteryl esters, cholesterol and phospholipids in small very low-density lipoprotein in the levothyroxine-treated pregnancies. In conclusion, levothyroxine treatment during pregnancy was associated with relatively small alterations in the blood metabolite profiles during pregnancy and labour.

Issue Information

Fri, 22 May 2026 06:14:58 -0700

Basic &Clinical Pharmacology &Toxicology, Volume 139, Issue 1, July 2026.