International journal of clinical pharmacology and therapeutics最新文献

Objective: This study aimed to investigate the baseline neutrophil count as a risk factor for ganciclovir-induced neutropenia in greater detail.

Materials and methods: This retrospective observational study included patients who received ganciclovir at Kindai University Nara Hospital between April 2006 and June 2023. Exclusion criteria were as follows: patients under 18 years of age, those who received chemotherapy within 2 weeks prior to ganciclovir administration, those who underwent blood transfusions or received granulocyte colony-stimulating factor injections during the observation period, those treated for fewer than 2 days, patients with a baseline neutrophil count < 1,000 cells/mm³, and patients with missing data on any study variables. The primary endpoint was the occurrence of severe neutropenia, which was analyzed using Cox regression analysis and the Cochran-Armitage trend test.

Results: To the 345 patients who met the inclusion criteria, exclusion criteria were applied, and 158 were ultimately identified as eligible patients. Patients with baseline neutrophil counts < 1,500 cells/mm³ were at significantly higher risk of severe neutropenia compared to those with baseline counts ≥ 4,000 cells/mm³ (HR = 16.86, 95% CI = 1.64 - 173.50, p = 0.018). Additionally, the incidence of severe neutropenia tended to increase significantly as the baseline neutrophil count decreased (p < 0.001).

Conclusion: These findings underscore the importance of monitoring baseline neutrophil counts before initiating ganciclovir treatment, particularly in patients with conditions associated with low neutrophil levels, such as hematological disorders.

Background: Berberine, a traditional Chinese medicine, has demonstrated significant therapeutic influences in treating diabetes, obesity, and diarrhea, among other conditions. It has exhibited potential therapeutic benefits for various neurodegenerative diseases, namely, Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD).

Aims: This study aims to elucidate the mechanism behind berberine pharmacological action in treating AD.

Materials and methods: We search the articles published in PubMed and CNKI and summarize the mechanism of berberine in AD.

Results: In recent years, as research into the pharmacology of berberine has deepened, researchers have discovered its strong neuroprotective properties. The ability of berberine to enhance cognitive function is thought to result from inhibiting the spread of AD-related proteins, reducing oxidative stress and inflammation, increasing choline levels, and regulating autophagy.

Conclusion: This review explores the latest research on berberine in AD, suggesting that berberine and its analogs may offer a promising new approach to treating the condition.

Objective: Cabotegravir is approved for HIV treatment (with rilpivirine) and prevention. The established cabotegravir population pharmacokinetic (PPK) model included 1.2% Asian participants. We aimed to compare cabotegravir pharmacokinetics between Asian and non-Asian populations and across Asian countries.

Materials and methods: Cabotegravir concentrations were collected from Asian participants in phase 1 and 3 studies. The applicability of the PPK model to Asian populations was validated by predicting the observed concentrations not included in model-building. Cabotegravir post-hoc pharmacokinetic parameters (long-acting absorption rate constant, weight-normalized apparent clearances and volumes of distribution) and exposures (trough and peak concentrations) following monthly and every-2-month regimens were estimated by fitting the PPK model to observed data. Non-Asian participants from the previous PPK dataset (1,697 males; 564 females) were used as comparator. Cabotegravir exposures in Asian and non-Asian were compared via simulations.

Results: 2,034 cabotegravir concentrations were collected from 162 Asian males (assigned male at birth) in China (n = 47), Japan (n = 17), Korea (n = 25), Thailand (n = 53), and Vietnam (n = 20), and 35 concentrations from 2 Asian females (assigned female at birth) in Korea. Cabotegravir pharmacokinetic parameters were similar between Asian and non-Asian participants. Cabotegravir exposures in Asian populations largely overlapped with but tended to be higher than non-Asian populations, suggesting similar efficacy. Cabotegravir exposures in Asian and non-Asian populations remained below the safety threshold, suggesting similar safety profiles. Cabotegravir pharmacokinetic parameters and exposures were similar across Asian countries.

Conclusion: No dose adjustment is recommended for Asian populations with and without HIV. Cabotegravir pharmacokinetic data from any Asian country/region may guide pharmacokinetic evaluation and regulatory considerations across Asian regions.

Aims: To investigate prescription patterns in children and adolescents receiving treatment for primary hypertension.

Materials and methods: Cumulative prescriptions within the 12-month period before the index date were analyzed for a cohort of 7,482 children and adolescents using Kaplan-Meier curves, stratified according to age group. Associations between age, sex, co-diagnoses, and the likelihood to be treated were evaluated using multivariable Cox regression.

Results: The percentage of adolescents, children aged 6 years and above, and children aged up to 5 years receiving antihypertensive therapy was low (15.7% for adolescents, 12.8% for children aged 6 years and above, and 10.3% for children aged up to 5 years). The numbers receiving an angiotensin-converting enzyme (ACE) inhibitor, the most frequently prescribed drug class, were 65.4, 70.3, and 62.8%, and the numbers receiving a β-adrenergic receptor blocker, the second most commonly prescribed drug class were 19.1, 16.7, and 14.0%, respectively. Using multivariable analysis, co-diagnoses for type 1 diabetes mellitus (HR: 2.47; 95% CI: 1.72 - 3.55) and epilepsy (HR: 2.46; 95% CI: 1.74 - 3.47) were significantly correlated with an increased likelihood to receive antihypertensive therapy.

Conclusion: The low number of children and adolescents with primary hypertension prescribed antihypertensive therapy is not in accord with current treatment guidelines. The reasons for this discrepancy and the effect it has on long-term cardiovascular outcomes are of considerable concern and need to be investigated.

Purpose: To evaluate skin toxicity associated with immune checkpoint inhibitors (ICIs) using data mining and the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

Materials and methods: Data on skin toxicity associated with the use of ICIs were retrieved for the period January 2011 to September 2023. Analysis was done using various methods, including reporting odds ratio (ROR) estimates, proportional reporting ratios (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker estimates (MGPS). Mortality and hospitalization data were also assessed.

Results: A total of 8,129 skin toxicity reports concerning "ICIs" as the "primary suspected cause" were documented, accounting for 18.89% of all reported adverse events. Anti-PD-1 agents showed the highest incidence of skin toxicity, whereas anti-CTLA-4 monotherapy was associated with the most significant changes in ROR, PRR, empirical Bayesian geometric mean (EBGM), and information component (IC) values. The median onset of toxicity was 17 days after commencement of ICI treatment, consistent across sexes, age groups, and ICI types. The highest mortality rate occurred with anti-PD-1 treatment (11.37%), and there was a significant difference in mortality rates between different ICI treatments (monotherapy vs. combination therapy) (p = 0.03).

Conclusion: Differences are present between ICI regimens in the pattern of skin toxicity with anti-PD-1 therapies exhibiting the highest incidence of skin toxicity and mortality rates, while anti-CTLA-4 therapies showed the most marked signals.

In recent years, immune checkpoint inhibitors, such as programmed death-1 (PD-1) inhibitors, have become key therapeutic options for specific cancers, used as first-, second-, or third-line treatments for various metastatic conditions. Nivolumab, a programmed death-1 (PD-1) inhibitor, is FDA-approved for metastatic renal cell carcinoma among other cancers. As the use of nivolumab becomes more widespread, understanding both its common and rare side effects is essential. Although nivolumab has been associated with autoimmune hemolytic anemia (AIHA), there are rare cases where this adverse effect may be compounded by other underlying conditions. Here, we report the first case of AIHA in a patient with glucose-6-phosphate dehydrogenase deficiency, triggered as a complication of nivolumab treatment.

Toripalimab, a humanized anti-PD-1 monoclonal antibody, is widely employed in the treatment of non-small cell lung cancer (NSCLC) and various other malignancies. However, there have been no reported cases linking prolonged administration of toripalimab to immune-mediated hepatitis (IMH). Typically, immune checkpoint inhibitor (ICI)-related IMH manifests within the first few weeks or months following the initiation of therapy. In this report, we presented a case of IMH in a patient with NSCLC following ~ 17 months of toripalimab treatment. IMH induced by toripalimab may occur at any time during treatment, underscoring the need for clinicians to remain vigilant in monitoring for adverse reactions. Throughout toripalimab treatment, careful attention must be paid to the symptoms, diagnosis, and pathological features of IMH. Glucocorticoids, such as methylprednisolone, can effectively reduce liver enzyme markers like aspartate aminotransferase and alanine aminotransferase in patients experiencing toripalimab-induced IMH.

Objective: Predicting the occurrence of hyperkalemia in patients undergoing co-trimoxazole treatment for Pneumocystis pneumonia is critical. However, other factors besides drug exposure affect serum potassium levels, and various interventions are often used to treat hyperkalemia in clinical practice. Therefore, we aimed to develop a Markov model to predict the risk of hyperkalemia under various intervention conditions.

Materials and methods: This was a retrospective, observational study. Information on daily dose of co-trimoxazole and hyperkalemia events was obtained from adult patients administered oral co-trimoxazole between 2015 and 2020 at Mie University Hospital (Mie, Japan). A Markov model with an intermediate layer was applied using NONMEM. The drug-effect model was assumed to have a maximum effective model. Bootstrapping and visual predictive checks were used to assess model validity.

Results: A total of 271 patients with 4039 observations of potassium levels were included. Baseline serum potassium level was a significant covariate of drug response. The successful bootstrap completion rate was 99.5%, and each parameter estimate was consistent with the bootstrap median; therefore, the model was sufficiently robust.

Conclusion: The Markov model, including an intermediate layer, provides a robust framework for predicting the risk of hyperkalemia, even in datasets where post-onset interventions vary from patient to patient. Thus, it is postulated that higher baseline potassium levels increase hyperkalemia.