International journal of clinical pharmacology and therapeutics最新文献

Objectives: To evaluate the indications and dosing regimens for oral metronidazole monotherapy (OMM) for the management of oral anaerobic infections (OAIs) other than periodontitis.

Materials and methods: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in literature of PubMed/Medline, Scopus, and Cochrane databases. Data were retrieved from reports published in English in the period January 1, 1980 - August 30, 2023. Joanna Briggs Institute Critical Appraisal Tools were used to assess study risk of bias.

Results: A total of 228 articles were retrieved from the databases of which 16 met the inclusion criteria necessary for achieving the aims of the study. OAIs in which OMM was used or recommended included pericoronitis; necrotizing ulcerative gingivitis/periodontitis/stomatitis, osteomyelitis, acute periapical infection, and cellulitis. OMM was prescribed in dosages ranging from 200 to 500 mg t.i.d. for periods ranging from 2 to 7 days. Osteomyelitis of the jaw was the only infection for which the dosage regimen of metronidazole was not clearly described.

Conclusion: Evidence from the databases searched support the view that OMM has clinical efficacy in the treatment of specific OAIs namely pericoronitis and necrotizing oral infections in immune-competent and immune-compromised patients. The evidence does not support the use of OMM in "deep tissue" infections such as osteomyelitis, and odontogenic infections such as acute apical infection and cellulitis. Clinical trials are warranted to determine the efficacy of OMM in comparison with other antibiotic regimens.

The global emergence of -COVID-19 has prompted rapid therapeutic and vaccine advancements; however, clinical evidence remains limited. With around a 50% fatality rate for COVID-19 patients with acute respiratory distress syndrome (ARDS), early intervention is crucial. This report details a severe case of post-COVID-19 thrombocytopenia in a 79-year-old man and emphasizes its critical nature. Despite negative initial COVID-19 test results, subsequent positive results led to treatment initiation, and severe thrombocytopenia persisted resulting in bleeding complications and death. Recognized as a hematological manifestation of COVID-19, thrombocytopenia in this geriatric patient highlights the need for extended post-COVID-19 monitoring and management. This underscores the importance of vigilance and timely intervention, especially in vulnerable populations, and emphasizes the need for further research to understand the intricate relationship between COVID-19 and thrombocytopenia.

Objective: To evaluate the bioequivalence of two different afatinib dimaleate formulations in healthy Chinese subjects under fasting conditions and to assess their pharmacokinetic and safety profiles.

Materials and methods: This randomized, open-label, 2-period, crossover, bioequivalence study included 32 healthy Chinese subjects. The subjects were assigned to receive a single 40-mg dose of generic or brand-named afatinib dimaleate tablet. Blood samples were collected pre-dose and up to 120 hours after dosing. Healthy subjects orally took the trial preparation (T) (afatinib maleate tablets developed by Jiangxi Shanxiang Pharmaceutical Co., Ltd., Gan Zhou, China) and the reference preparation (R) (afatinib maleate tablets developed by Boehringer Ingelheim Pharma GmbH & Co., Ingelheim, Germany) under fasting conditions in the appropriate period according to the randomization. We measured the blood concentrations, calculated the pharmacokinetic parameters of the two preparations in the human body, and evaluated whether formulations were bioequivalent. Safety of the preparations in healthy subjects was monitored during the whole trial. Safety assessment was conducted by vital signs, physical examination, laboratory examination, and 12-lead electrocardiogram during the study, i.e., from the time the subject received the test drug to the end of the last visit.

Results: Under fasting conditions, the 90% confidence intervals (CIs) of the geometric mean ratios of the test/reference for afatinib dimaleate were 93.34 - 103.92% for AUC_0-t, 90.26 - 105.52% for C_max, and 93.49 - 104.05% for AUC_0-∞.

Conclusion: The 90% CI for the geometric mean ratios (test/reference) of C_max, AUC_0-t, and AUC_0-∞ were within the range of 80.00 - 125.00%, indicating that the test formulation was equivalent to the reference formulation in healthy Chinese subjects under fasting conditions. Both products were similar in terms of safety.

Pulmonary fibrosis (PF) is a chronic and progressive pulmonary interstitial disease of unknown etiology and is also a sequela in severe patients with the Coronavirus Disease 2019 (COVID-19). Seven databases were systematically searched to evaluate the preclinical evidence of Tanshinone IIA (Tan IIA) on PF. The quality of the included studies was assessed using a 10-item risk of bias tool, and data were analyzed using RevMan 5.3 software. 22 experiments from 12 studies on a total of 248 animals were included. The results showed that PF phenotype, such as fibrotic score, collagen I (Col-I), collagen III (Col-III), hydroxyproline (Hyp), in the group treated with Tan IIA were significantly lower than those in the model group (p < 0.00001). The potential mechanisms of Tan IIA improvement of PF involve reducing inflammation, antioxidation, and suppressing activation of transforming growth factor beta 1 (TGF-β1). The subgroup analysis of different models, different rat species, and different dosage time showed significant reduction in fibrotic scores and Hyp levels with Tan IIA. The preclinical evidence indicated that Tan IIA might be a potent and promising agent for PF, but this conclusion should be further confirmed with more research.

Background: Obesity is a complex disease for which pharmacotherapy is often used. Anti-obesity drugs (AODs) are characterized by inducing a variable inter-subject body weight reduction (BWR), the attainment of a plateau after their maximal effect is achieved, and weight regain after drug discontinuation, which complicate individualized treatment of obesity.

Objective: This exploratory analysis aimed to compare the first-month body weight reduction in kg (1mo-BWRkg) and tolerance development (moT) of four known interventions with low (placebo), intermediate (phentermine or mazindol monotherapy), and high (5 active ingredients fixed-dose combination) efficacy, as predictors of their 6-month body weight reduction efficacy in percent (6mo-BWR%). In addition, a detailed analysis of the 6-to-12-month BWR follow-up in subjects under orlistat or diet and exercise regimens was performed.

Materials and methods: The analysis included 662 adult subjects with obesity. After the construction of average efficacy and weight rebound curves, subjects were grouped into various 1mo-BWRkg, moT, and 6mo-BWR% intervals, or 6-month body weight rebound parameters for further evaluation.

Results: The 6mo-BWR% efficacy level of interventions was confirmed, although a general high intersubject variation was observed. 1mo-BWRkg + moT was found as an acceptable predictor of 6mo-BWR%. Between 50 and 80% of the 6-to-12-month follow-up completers maintained at least 5% BWR%.

Conclusion: Short-term AODs are useful adjuvants for the 1-year rational treatment of obesity. 1mo-BWRkg + moT is an acceptable parameter to predict the 6mo-BWR% efficacy of these interventions.

Objective: To assess the safety, tolerability, and effectiveness of the intravenous immunoglobulin (IVIG) Intratect 50 g/L in immunoglobulin replacement therapy (IgRT) in a prospective, large-scale non-interventional study (NIS). The analysis focused upon patients with secondary immunodeficiency (SID), the most frequent indication for IgRT in this NIS.

Materials and methods: Patients were enrolled at 123 centers in Germany. Each patient received IVIG as prescribed by the physician, guided by the Summary of Product Characteristics. Data were acquired from medical records and patients' questionnaires.

Results: In the NIS, 3,563 patients were documented. The main indication for IgRT was SID (73.2%), followed by primary immunodeficiency (14.7%), immune thrombocytopenia (5.8%), and other indications (6.2%). Among the SID patients, 52.9% were male, mean age was 66.5 years, and most (63.8%) were IVIG-naïve. Their annual infection rate improved from 3.7 before documentation in the NIS to 1.1 during the first year of the study. IgG trough plasma levels increased during treatment (> 6 g/L: 44.5% of SID patients at study entry and 64.8% in long-term treatment) and were associated with a trend toward reduced infection rate (p = 0.08). A 1-year infection analysis showed a significantly lower infection risk in the medium- and high-dose groups than in the low-dose group (p = 0.028 and p = 0.017, respectively). Patients' treatment satisfaction and quality of life improved from baseline. Adverse drug reactions (ADRs) in SID occurred at a low frequency with 0.8% at infusion level. On the patient level, ADRs occurred in 251 (15.3%) SID patients, with chills (7.4%) and pyrexia (0.9%) reported most frequently.

Conclusion: Effectiveness, safety, and quality of life confirmed the positive benefit-risk profile of IgRT. Higher IVIG dosages per body weight led to higher IgG plasma trough levels, in turn leading to reduced infection rates. Obese patients may need body-weight-adjusted treatment to reduce the risk of infection.

Objective: This study aimed to analyze the pharmacokinetic (PK) characteristics, safety, and bioequivalence (BE) of a test (T) preparation of a nifedipine controlled-release tablet and the reference (R) drug (Adalat GTIS) in Chinese study participants in the context of fasting and postprandial states.

Materials and methods: An open-label, single-center, randomized, single-dose, two-period study was designed including two separate arms, one with administration under fasting conditions and one with administration under postprandial conditions (high-fat, high-calorie breakfast). After oral administration, the nifedipine concentrations in plasma were quantitatively analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) at regular intervals. Primary PK parameters, including the area under the concentration curve from 0 to infinity (AUC_0-∞), the area under the concentration profile from 0 to the last measurable concentration time (AUC_0-t), and maximal measured plasma concentration (C_max) were log-transformed with BE limits of 80 - 125% to evaluate BE. All adverse events (AEs) were wholly supervised.

Results: The PK profiles of the T and R formulations were comparable to each other under both fasting and postprandial conditions. The 90% confidence intervals (CIs) of the AUC_0-∞, AUC_0-t, and C_max were 92.69 - 106.06%, 93.32 - 107.05%, and 99.53 - 116.71%, respectively, under the fasting state. The 90% CIs of the AUC_0-∞, AUC_0-t, and C_max were 105.05 - 117.40%, 105.43 - 117.82%, and 102.66 - 116.30%, respectively, in the postprandial arm. 47 cases of drug-associated AEs were noted in the entire research.

Conclusion: Under both the fasting and postprandial states, the two nifedipine controlled-release formulations were bioequivalent and safe in healthy Chinese subjects.

A variety of drugs have been known to induce disulfiram-like reactions in individuals exposed to ethanol, including certain cephalosporin antibiotics with methylthiotetrazole (MTT) substituents or methylthiodioxotriazine (MTDT) rings. Among cephalosporins, cefixime is known to cause fewer disulfiram-like reactions. This case report, the first involving a pediatric patient, presents the scenario of a 14-year-old female who exhibited drowsiness, loss of consciousness, and cold extremities within an hour after ingesting 9 cefixime capsules. Upon admission, drug intoxication was considered, prompting immediate gastric lavage and toxicology tests, which revealed the presence of both cefixime and alcohol. Subsequent monitoring of vital signs, rehydration, and symptomatic treatments aimed at facilitating toxic excretion were administered during hospitalization. Following initial assessment by a clinical pharmacist, drug intoxication was deemed improbable, though an atypical disulfiram-like reaction or alcohol intoxication could not be ruled out. Further evaluation, coupled with the child's cefixime overdose, suggested an atypical disulfiram-like reaction. This case underscores the potential for disulfiram reactions even with cephalosporins lacking MTT substituents or MTDT rings. Notably, it is the first report of an atypical disulfiram-like reaction triggered by alcohol consumption following cefixime overdose, emphasizing the importance of caution in cefixime usage and avoidance of alcohol or alcohol-containing substances.

Objectives: This study aimed to understand the pharmacokinetics of ticagrelor in Chinese patients with acute coronary syndrome (ACS), identify influencing factors, and inform ticagrelor treatment optimization.

Materials and methods: Data from 195 ACS patients, including 491 plasma ticagrelor concentration timepoints and clinical information, were analyzed using NONMEN for pharmacokinetic (PK) parameter factors. The model underwent internal validation with bootstrap methodology.

Results: The PK curve of ticagrelor was well delineated using a one disposition compartment model with first-order absorption rate constant, 0.67/h. When the direct bilirubin levels and white plasma cell counts increased, female patients showed decreased glomerular filtration rate, decreased ticagrelor clearance rate, and increased exposure. When the direct bilirubin levels increased and body weight and hemoglobin decreased, rs6787801 was GG compared with AA and GA, the ticagrelor metabolite clearance rate decreased and exposure increased.

Conclusion: The study offers key insights into ticagrelor's dose-exposure relationship post-percutaneous coronary intervention in ACS patients, highlighting factors critical for personalized treatment strategies.