International journal of clinical pharmacology and therapeutics最新文献

Objectives: This study aimed to develop a minimal physiologically based pharmacokinetic (mPBPK) model to predict the biodistribution of silica nanoparticles (SiNPs) and evaluate how variations in surface charge, size, porosity, and geometry influence their systemic disposition.

Materials and methods: The mPBPK model was calibrated using in vivo pharmacokinetic data from mice administered aminated, mesoporous, and rod-shaped SiNPs. Human data were collected from clinical trial data from Cornell dots. The mPBPK model incorporated physiological parameters and nanoparticle-specific characteristics to simulate SiNP biodistribution and was built in Matlab 2024a. Global sensitivity analysis identified influential parameters, including the unbound fraction and elimination rate constants for the kidneys and mononuclear phagocyte system (MPS). The model was extrapolated to predict human pharmacokinetics, with accuracy evaluated using Pearson correlation coefficients. Non-compartmental analysis (NCA) assessed organ-specific accumulation and biodistribution patterns.

Results: Global sensitivity analysis revealed that the unbound fraction and elimination rate constants for the kidneys and MPS were major determinants of SiNP biodistribution. NCA indicated that aminated SiNPs initially accumulated in the liver, spleen, and kidneys but redistributed due to their high unbound fraction, while mesoporous SiNPs localized in the lungs. Rod-shaped SiNPs exhibited high lung exposure. The extrapolated model showed high predictive accuracy, with Pearson correlation coefficients of 0.98 for mice and 0.99 for humans.

Conclusion: The mPBPK model effectively predicts the pharmacokinetics of diverse SiNPs, offering insights to optimize nanoparticle-based drug delivery systems and facilitating their translation from preclinical models to clinical applications.

Objective: To investigate the analgesic effect of sufentanil plus dexmedetomidine following cesarean section and to determine its influence on placental hypoxia-inducible factors.

Materials and methods: A cohort of 150 puerperae who underwent prenatal examinations and cesarean section in our hospital were randomized into a control group (n = 75) and a study group (n = 75). Anesthesia and analgesia were carried out using sufentanil alone in the control group and sufentanil plus dexmedetomidine in the study group. Measurements were made before anesthesia (T0), 5 minutes (T1) and 10 minutes (T2) after anesthesia, and immediately after delivery (T3) and after the end of surgery (T4).

Results: Mean arterial pressure (MAP) and heart rate (HR) decreased in both groups at T1 - T4 compared with T0, but were higher in the study group compared to the control group (p < 0.05). The visual analogue scale (VAS) score, and levels of substance P (SP), neuropeptide Y (NPY) and malondialdehyde (MDA) in the study group were lower than those in the control group (p < 0.05). The beginning and duration of labor and the dose of analgesics within the 48-hour observation period were all lower in the study group compared to the control group (p < 0.05).

Conclusion: Sufentanil plus dexmedetomidine can effectively maintain hemodynamic stability during cesarean section without marked changes in placental hypoxia-inducible factors and oxidative stress responses and has a limiting effect on the secretion of pain mediators.

Background: Black patients experience a disproportionately high incidence of heart failure with reduced ejection fraction (HFrEF), where vasodilators serve as a key therapeutic strategy.

Materials and methods: A retrospective cohort study based on medical records of Black patients with HFrEF and an ex vivo analysis of mouse thoracic aorta stimulated with empagliflozin (empa) and hydralazine-isosorbide dinitrate (H-ISDN).

Results: The combination synergistically activated cyclic guanosine monophosphate (cGMP) production in the ex vivo thoracic aorta and improved kidney function, reduced brain natriuretic peptide (BNP), and lowered mortality compared to H-ISDN alone in HFrEF patients.

Conclusion: Empa + H-ISDN offered superior benefits in Black patients with HFrEF, possibly by reducing oxidative stress and enhancing nitric oxide (NO) bioavailability.

A patient with advanced small cell lung cancer presented with systemic skin pigmentation, a rare and severe skin adverse reaction during treatment with osimertinib. Osimertinib-induced hyperpigmentation is rarely reported, According to the patient's condition, adverse drug reactions, and drug efficacy, osimertinib was the urgently needed treatment regimen, and 80 mg of osimertinib was continued. Therefore, we hope this case can provide experience for clinicians to identify adverse reactions of the drug and ensure the safety of patients.

Aims: To explore the association of epithelial-mesenchymal transition (EMT)-related biomarkers with an increase in disease severity/progression leading to readmission with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Materials and methods: A prospective and observational study was conducted, involving patients admitted for AECOPD. Serum levels of EMT-related biomarkers (E-cadherin, zonula accludens-1 (ZO-1), vimentin and α-smooth muscular actin (α-SMA) were measured at patient admission. The clinical outcomes were 12-month AECOPD-related readmission risk, time to the first AECOPD-related readmission after discharge and number of 12-month AECOPD-related readmissions.

Results: A total of 168 patients were included in the study, of whom 54 had at least one readmission for AECOPD during the 12-month follow-up period. Low serum levels of E-cadherin (< 279.7 ng/mL, adjusted odds ratio (aOR) = 9.434, p = 0.000), and high serum levels of vimentin (≥ 263.2 pg/mL, aOR = 7.116, p = 0.008), and α-SMA (≥ 460.8 pg/mL, aOR = 11.653, p = 0.000) were associated with an increased risk of AECOPD-related readmissions. Patients with low serum levels of E-cadherin and high serum levels of α-SMA exhibited the highest risk of AECOPD-related readmission. Additionally, low serum levels of E-cadherin and high serum levels of vimentin and α-SMA were associated with a shorter time to the first AECOPD-related readmission, and an increased number of 12-month AECOPD-related readmissions.

Conclusion: Low serum levels of E-cadherin and high serum levels of vimentin and α-SMA are associated with an increase in disease severity/progression leading to AECOPD-related readmissions during a 12-month follow-up period. Moreover, simultaneous evaluation of E-cadherin and α-SMA levels enhances the accuracy in identifying patients who are likely to be re-hospitalized with AECOPD.

Background: Exogenous insulin antibody syndrome (EIAS) is a rare allergic reaction triggered by exogenous insulin. It typically manifests as recurrent hypoglycemia during insulin use. In some cases, patients may also experience significant elevation in their blood glucose levels.

Case report: We review a case of type 2 diabetes mellitus complicated by diabetic ketoacidosis. The patient exhibited a significant increase in his blood glucose level and demonstrated a substantial insulin resistance. Only through the administration of a large amount of insulin, it was possible to gradually reduce his blood glucose level. Notably, laboratory examination revealed a significant elevation in the patient's blood insulin autoantibody. Based on these findings, the patient was diagnosed with EIAS and used glucocorticoids during treatment. Subsequently, the patient's required insulin dose decreased significantly, and the blood glucose level was effectively controlled.

Conclusion: EIAS can significantly increase blood glucose levels and impair the hypoglycemic effect of insulin. In patients with acute metabolic disorders, such as ketoacidosis, glucocorticoid therapy can be considered.

Neurodegenerative diseases such as Alzheimer's and Parkinson's are marked by neuronal loss due to oxidative stress, neuro inflammation, and lipid dysregulation. Medium-chain triglyceride (MCT) oil, particularly rich in caprylic acid (C8, 56%) and capric acid (C10, 43%), has shown potential neuroprotective effects through its antioxidant properties, cholinesterase inhibition, and lipid-lowering benefits.

Objectives: This study aims to evaluate the neuroprotective effects of ORGAHEAL medium-chain triglyceride (MCT) oil by assessing its antioxidant activity, cholinesterase inhibition, and lipid-lowering effects in vitro.

Materials and methods: Antioxidant activity was measured using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide scavenging assays. Cholinesterase inhibition was studied through enzyme kinetics with Lineweaver-Burk and Dixon plots. Lipid-lowering effects were analyzed in 3T3-L1 adipocytes using Oil Red O staining and triglyceride quantification.

Results: MCT oil exhibited antioxidant activity in DPPH and nitric oxide assays (IC50: 6.15 mg/mL and 29.87 mg/mL) and non-competitive inhibition of acetylcholinesterase and butyrylcholesteraseE (Ki: 31.01 mg/mL and 24.86 mg/mL). It reduced lipid accumulation and triglyceride levels in 3T3-L1 cells, potentially enhancing neuronal health by lowering oxidative damage.

Conclusion: MCT oil, with caprylic acid (C8) and capric acid (C10), offers neuroprotective benefits through its antioxidant, cholinesterase inhibitory, and lipid-lowering properties. Further in vivo studies are needed to confirm its therapeutic potential.

This open-label, randomized, single-dose, 4-period, 2-sequence, fully replicated study was conducted to evaluate the bioequivalence of tamsulosin 0.4 mg sustained-release film-coated tablet manufactured by PT Dexa Medica, Indonesia, and Harnal OCAS 0.4 mg prolonged-release tablet manufactured by Astellas Pharma Europe B.V., the Netherlands, imported by PT Combiphar, Indonesia, under fasting conditions in 28 healthy adult Indonesian males. Subjects were randomly assigned to receive the test formulation (1 single tablet of 0.4 mg) or the reference formulation (1 single tablet of 0.4 mg) orally in each of the 4 study periods, according to the full replicate design. Therefore, over the 4 complete periods, each subject received 2 administrations of the test formulation and 2 administrations of the reference formulation, with each administration separated by a 7-day washout period. The plasma concentration of tamsulosin from the blood samples was analyzed using validated ultra-performance liquid chromatography with tandem mass spectroscopy detection (UPLC-MS/MS), and pharmacokinetic parameters (AUC_0-t, AUC_0-∞, C_max, t_max, and T_1/2) were calculated. The 90% confidence interval (CI) for the test/reference geometric mean ratio (GMR) of the AUC_0-t was 80.2 - 98.4%, and for AUC_0-∞ it was 80.5 - 120.1%. The 90% CI GMR of C_max was 89.3 - 107.7%. All parameters were within the 90% CI GMR acceptance criteria of 80.0 - 125.0%. The T_1/2 and t_max of the 2 test drugs and the 2 reference drugs were not statistically different. There was no adverse effect observed during the study. Based on the study results, it was concluded that both tamsulosin formulations were bioequivalent and well tolerated.

Background: The development of delirium is closely linked to inflammatory processes. Omega-3 fatty acids can modulate the immune response and may contribute to reducing the incidence of sepsis-associated delirium (SAD).

Aims: To investigate the effects of omega-3 fatty acids on delirium in patients with sepsis.

Materials and methods: In a single-center clinical trial, 220 intensive care patients diagnosed with sepsis were randomly assigned to receive daily intravenous infusions of either an omega-3 fish oil emulsion or a placebo. Delirium was assessed twice daily using the Richmond Agitation-Sedation Scale (RASS) and the Confusion Assessment Method (CAM). The primary outcome was the duration of delirium during the first 10 days of admission. Secondary outcomes included the duration of mechanical ventilation, length of intensive care unit (ICU) stay, and mortality.

Results: Compared to the control group, the omega-3 group exhibited significantly fewer days with delirium episodes (p = 0.010), shorter ICU stays (p = 0.008), and fewer mechanical ventilation days (p = 0.001). However, there was no statistically significant difference in mortality between the two groups.

Conclusion: Omega-3 fatty acids may effectively reduce the risk of delirium in sepsis patients, highlighting their potential as a therapeutic intervention in this population.