International journal of clinical pharmacology and therapeutics最新文献

A characteristic toxicity of niraparib is a decrease in blood platelets (PLT), with an incidence of ~ 34% for grades 3 - 4 conditions. However, exceedingly severe cases have been reported infrequently. This paper describes three patients with acute and refractory severe PLT deficiency due to niraparib administration. The symptom characteristics, treatment course, and outcomes have also been analyzed, and the potential for the involvement of immune-related factors is considered. Therefore, it is recommended to comprehensively assess bone marrow hematopoietic function and high-risk variables before administering niraparib, intensify self-management and monitoring of patients, track changes in indicators, and intervene promptly. Additionally, if standard PLT-elevating therapies are ineffective, early full-dose administration of thrombopoietin receptor agonists, preferably avatrombopag, may be beneficial for reversing PLT loss of control.

Objective: This study aimed to detect cardiovascular disease-related signals using Global Individual Case Safety Report data on JAK inhibitors.

Materials and methods: A signal detection study was conducted using the WHO-UMC VigiBase.

Results: This study identified four cardiovascular adverse event signals associated with JAK inhibitors in Asian populations, including pulmonary embolism, deep vein thrombosis, thrombosis, and cerebrovascular accidents.

Conclusion: Analysis of Asian populations revealed a higher risk of thromboembolic events associated with JAK inhibitors than with TNF inhibitors. However, unlike in the Western populations, no myocardial infarction signal was detected in the Asian populations.

Introduction: Sunitinib is an oral drug approved for the treatment of metastatic renal cell carcinoma. Serious cutaneous adverse reactions to sunitinib are rare, and when they occur, discontinuation of the treatment may be needed.

Case report: A 70-year-old male patient was diagnosed with stage IV clear cell renal carcinoma and received treatment with sunitinib. After a second cycle with a 25% dose reduction, the patient was admitted with a diagnosis of grade 3 genital erythema. After ruling out other common causes, sunitinib was considered the cause of genital erythema and was stopped. Treatment with corticosteroids, topical applications, and morphine was started, with resolution after 18 days of evolution.

Discussion: There are only a few published reports that describe erythema and scaling of the genital skin. As in those few cases, for our patient, the first clinical signs appeared on day 28 of sunitinib treatment, and the lesions disappeared after 2 weeks without the use of the drug. Erythema and scaling reappeared when the drug was reintroduced, with greater severity than what was described in some of the other cases, which even included cases for which the lesions did not reappear.

Conclusion: Rare instances of severe and limiting skin toxicity may necessitate treatment suspension and compromise survival, as observed in our case. It is crucial to recognize these skin toxicities and understand their appropriate management strategies to initiate treatment as early as possible, thereby avoiding hospitalizations and enabling the resumption of sunitinib therapy.

Aims: To assess the renoprotective effects of dulaglutide and identify mechanisms of action in patients with type 2 diabetes and diabetic kidney disease (DKD).

Materials and methods: Outpatients/ambulant patients at the Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University between October 2021 and July 2023, with type 2 diabetes and DKD, a urinary albumin-to-creatinine ratio (UACR) ≥ 3 mg/mmol and who were receiving hypoglycemic agents were prescribed dulaglutide at a dose rate of 0.75 - 1.5 mg once weekly (intervention group; n = 70). Patients receiving hypoglycemic agents other than glucagon-like peptide-1 (GLP-1) receptor agonists and who were not prescribed dulaglutide constituted the control group (n = 65). Observations/outcomes: The primary outcome was a change in the UACR and biomarkers of epithelial-mesenchymal transition (EMT) determined after 12 months of intervention treatment. Adverse events (estimates of tolerability and safety) were recorded during treatment and a follow-up period of 12 months.

Results: UACR changes in the intervention group compared to the control group were significantly lower (p < 0.01 at 6 months and p < 0.05 at 12 months). The frequency of gastrointestinal adverse events in the two groups were not significantly different, and there were no significant increases in the number of hypoglycemic events. Dulaglutide significantly increased the epithelial marker E-cadherin and inhibited the mesenchymal marker periostin.

Conclusion: It is concluded that dulaglutide causes significant reductions in urinary albumin and modulates EMT-related proteins thereby ameliorating the decline in kidney function in patients with type 2 diabetes and DKD.

Objective: To assess the effects of bisphosphonates (zoledronic acid injection) plus alendronate sodium on bone mineral density (BMD) and levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and insulin-like growth factor I (IGF-I) in patients with osteoporosis.

Materials and methods: A total of 94 patients recruited from osteoporosis patients hospitalized in the period October 2021 to December 2022 were assigned to either a control group or an observation group using a random number table. The control group was treated with alendronate sodium alone, whereas the observation group received zoledronic acid injection in combination with alendronate sodium administered orally.

Results: Pre-treatment values for BMD, serum levels of IL-6, TNF-α, and IGF-I did not differ between the two groups (p > 0.05). However, post-treatment BMD measured at the femoral neck, in lumbar vertebrae, and Ward's triangle were increased, as was serum IGF-I level (p < 0.05). In contrast, in comparison with the control group, reductions were observed in serum IL-6 and TNF-α (p < 0.05). The incidence of adverse reactions such as nausea and vomiting, diarrhea, musculoskeletal pain, and hypocalcemia was significantly lower in the observation group (p < 0.05).

Conclusion: Zoledronic acid injection in combination with alendronate sodium increases the expression of IL-6, TNF-α, and IGF-I, suppresses bone resorption and promotes bone recovery in patients with osteoporosis.

Aims: The aims of this study were to evaluate and compare the pharmacokinetic profiles and establish bioequivalence of test and reference teriflunomide tablets (Aubagio) in healthy Chinese male subjects under fasting and fed conditions.

Materials and methods: Subjects were randomly assigned to either the fasting or the fed group and also to one of the two treatment sequences (test-reference or reference-test), according to which they received a single 14-mg dose of the test or reference teriflunomide tablet in the study periods. During each period, blood samples were collected at pre-dose and at intervals up to 72 hours after dosing. After 72 hours post dose, an accelerated elimination procedure using cholestyramine 4 g t.i.d. PO was done. Plasma concentrations of teriflunomide were determined by liquid chromatography-tandem mass spectrometry. The safety of both tablets was monitored throughout the study.

Results: 48 subjects were enrolled, and all completed the study, with 24 participants each in the fasting and fed groups. In both groups, the 90% confidence intervals for AUC_0-72h and C_max were within the acceptable bioequivalence range (80 - 125%). There were no significant differences in adverse event (AE) reporting between the subjects receiving test or reference tablet. No serious AEs occurred during the study period.

Conclusion: The test teriflunomide tablet was pharmacokinetic bioequivalent to the reference teriflunomide tablet (Aubagio) in healthy Chinese male subjects under both fasting and fed conditions. Both formulations were well tolerated by all study participants.

Objective: To assess the effects of atomizing inhalation of antibiotics on germ clearance rate and adverse reactions in respiratory infectious diseases.

Background: Atomizing inhalation of antibiotics is an innovative local drug delivery strategy.

Material and methods: PubMed, Medline, and Web of Science were searched systematically for appropriate clinical studies on atomizing inhalation of antibiotics for respiratory infectious diseases (patients diagnosed with respiratory infectious diseases; intervention: atomizing inhalation of antibiotics; comparison: oral or intravenous administration). Basic data recorded: sample size, follow-up time, germ clearance rate, adverse reactions and other outcome indicators. A meta-analysis was performed using RevMan 5.3 software.

Results: Six independent studies involving 245 patients with respiratory infectious diseases were included. There were 131 patients in the experimental group using atomizing inhalation of antibiotics and 114 patients in the control group utilizing oral or intravenous administration. Atomizing inhalation of antibiotics significantly increased the germ clearance rate (defined by no organism growth in culture and no visible organisms), and reduced number, frequency, and severity of adverse reactions compared with the controls.

Discussion: The advantages of atomizing inhalation of antibiotics may be attributed to the direct working of drugs on the infection site, increasing local drug concentrations, and thus killing germs more effectively. However, there are differences in the types and doses of antibiotics, atomizing units, and underlying diseases of patients across studies.

Conclusion: Atomizing inhalation of antibiotics exerts significantly better germ clearance effects while decreasing the incidence of adverse reactions than does oral or intravenous administration in the treatment of respiratory infectious diseases.

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.