Clinical Pharmacology : Advances and Applications最新文献

Dexmedetomidine is a selective and potent α₂-adrenoceptor agonist used for sedation, analgesia, and anxiolysis, with minimal respiratory depression; therefore, it is widely used in clinical practice. Transient hypertension has been reported to be an indication for the use of dexmedetomidine. The authors report three female patients who experienced hypertensive crisis when used atropine to treat bradycardia caused by dexmedetomidine. The transient hypertension is a relatively common side effect of dexmedetomidine, hypertensive crisis seen with coadministration of atropine is much less frequently reported. This is the first report to describe the use of atropine to treat bradycardia induced by dexmedetomidine, which may cause severe hypertension in female patients. They discuss the reason for and treatment of hypertension caused by administration of atropine and dexmedetomidine together and review the relevant literature.

Medication errors have the potential to cause serious toxicity and hospitalization. This case report describes a 25-year woman who suffered serious side effects and was ‎hospitalized after receiving intravenous ipratropium bromide/salbutamol. This was due to a medication error in its preparation and administration. The caregiver diluted an intravenous antibiotic with the incorrect diluent (nebulizer solution), which led to serious toxicity, including acute urine retention and sinus tachycardia, and then resulted in patient hospitalization. A literature review of case reports was conducted to compare and identify the pattern of ipratropium/salbutamol-induced acute urinary retention. The present report underscores the importance of clinical awareness about medication-induced acute urine retention. Furthermore, it is crucial that physicians inform and educate the patients and their carers about double-checking doses and labelling before administering medication, particularly for intravenous drugs.

Allopurinol is a commonly used medication that lowers uric acid production which is essential for gout treatment and prevention. Although many patients tolerate allopurinol therapy without severe complications; Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are life-threatening delayed hypersensitivity reactions that have been reported especially among Asian and African American patients. We describe a case of allopurinol-induced SJS in a 95-year-old Asian female. The patient started allopurinol 13 days prior to presenting to the emergency room (ER). On day 10 of therapy, the patient developed a diffuse erythematous desquamating rash which prompted her to visit the ER after 3 days from the rash onset. This case report describes a rare fatal hypersensitivity reaction that requires rapid identification and treatment in a multi-disciplinary setting.

Background: Emergence of antimalarial drugs and insecticides resistance alarms scientists to develop a safe and effective malaria vaccine. A pre-erythrocytic malaria vaccine called RTS,S has made great strides.

Aim: The review was aimed to assess the safety of the candidate malaria vaccine RTS,S with AS01 and AS02 adjuvants using data from Phase I-III randomized controlled clinical trials (RCTs).

Methods: This systematic review was conducted based on PRISMA 2020. Regardless of time of publication year, all articles related with safety of RTS,S, RCTs published in the English language were included in the study. The last search of databases, and registry was conducted on 30 May, 2022. Pubmed, Google Scholar, Cochrane Library, Wiley Online Library, and Clinical trials.gov were thoroughly searched for accessible RCTs on the safety of RTS,S malaria vaccine. The studies were screened in three steps: duplicate removal, title and abstract screening, and full-text review. The included studies' bias risk was assessed using the Cochrane risk of bias tool for RCTs. This systematic review is registered at Prospero (registration number: CRD42021285888). The qualitative descriptive findings from the included published studies were reported stratified by clinical trial phases.

Findings: A total of thirty-five eligible safety studies were identified. Injection site pain and swelling, febrile convulsion, fever, headache, meningitis, fatigue, gastroenteritis, myalgia, pneumonia, reactogenicity, and anemia were the most commonly reported adverse events. Despite few clinical trials reported serious adverse events, none of them were related to vaccination.

Conclusion: Most of the adverse events observed from RTS,S/AS01 and RTS,S/AS02 malaria vaccines were reported in the control group and shared by other vaccines. Hence, the authors concluded that both RTS,S/AS01 and RTS,S/AS02 malaria vaccines are safe.

Purpose: Patients admitted with neurocritical illness are presumed to be at high risk for venous thromboembolism (VTE). The administration of chemical and/or mechanical VTE prophylaxis is a common practice in critically ill patients. Recent data did not show a significant difference in the incidence of VTE between chemical compared to a combined chemical and mechanical VTE prophylaxis in critically ill patients with limited data in neurocritically ill population. The objective of this study is to investigate the incidence of VTE between chemical alone compared to chemical and mechanical VTE prophylaxis in neurocritically ill patients.

Patients and methods: This was a retrospective cohort study at a tertiary teaching hospital. Data were obtained from electronic medical records for all patients admitted with neurocritical illness from January 1, 2016, to December 31, 2020. Patients were excluded if they did not receive VTE prophylaxis during admission or were younger than 18 YO. Major outcomes were symptomatic VTE based on clinical and radiological findings, intensive care unit (ICU) length of stay (LOS), and hospital LOS. Minor outcomes included severe or life-threatening bleeding based on GUSTO criteria, and mortality at 28-days.

Results: Two hundred and twelve patients were included in this study. Patients did not have any significant differences in their baseline characteristics. The incidence of VTE was similar in the chemical only group compared to the combined VTE prophylaxis group (19/166 (11.3%) vs 7/46 (15.2%)); P = 0.49. No difference between groups in their ICU LOS 6 [3-16.2] vs 6.5 [3-19]; P = 0.52, nor their mortality (18/166 (10.7%) vs 3/46 (6.5%)); P = 0.38, respectively. Less bleeding events were seen in the chemical prophylaxis group compared to the combined VTE prophylaxis group (19/166 (11.3%) vs 12/46 (26.1%); P = 0.01).

Conclusion: Our findings observed no difference between the administration of chemical VTE prophylaxis alone compared to the combined VTE prophylaxis strategy. More data are needed to confirm this finding with more robust methodology.

Background: In addition to the maximum plasma concentration (C_max) to the minimum inhibitory concentration (MIC) ratio, the 24-hour area under the concentration-time curve (AUC_24h) to MIC has recently been suggested as pharmacokinetic/pharmacodynamic (PK/PD) targets for efficacy and safety in once-daily dosing of gentamicin (ODDG) in critically ill patients.

Purpose: This study aimed to predict the optimal effective dose and risk of nephrotoxicity for gentamicin in critically ill patients for two different PK/PD targets within the first 3 days of infection.

Methods: The gathered pharmacokinetic and demographic data in critically ill patients from 21 previously published studies were used to build a one-compartment pharmacokinetic model. The Monte Carlo Simulation (MCS) method was conducted with the use of gentamicin once-daily dosing ranging from 5-10 mg/kg. The percentage target attainment (PTA) for efficacy, C_max/MIC ~8-10 and AUC_24h/MIC ≥110 targets, were studied. The AUC_24h >700 mg⋅h/L and C_min >2 mg/L were used to predict the risk of nephrotoxicity.

Results: Gentamicin 7 mg/kg/day could achieve both efficacy targets for more than 90% when the MIC was <0.5 mg/L. When the MIC increased to 1 mg/L, gentamicin 8 mg/kg/day could reach the PK/PD and safety targets. However, for pathogens with MIC ≥2 mg/L, no studied gentamicin doses were sufficient to reach the efficacy target. The risk of nephrotoxicity using AUC_24h >700 mg⋅h/L was small, but the risk was greater when applying a C_min target >2 mg/L.

Conclusion: Considering both targets of Cmax/MIC ~8-10 and AUC_24h/MIC ≥110, an initial gentamicin dose of 8 mg/kg/day should be recommended in critically ill patients for pathogens with MIC of ≤1 mg/L. Clinical validation of our results is essential.

Purpose: In people with type 2 diabetes mellitus (T2DM), both glucose metabolism abnormalities and atherosclerosis risk are significant concerns. This study aims to investigate the effects of the sodium-glucose cotransporter 2 inhibitor tofogliflozin (TOFO) and the dipeptidyl peptidase-4 inhibitor anagliptin (ANA) on markers of glucose metabolism and atherosclerosis when administered individually or in combination.

Methods: Fifty T2DM patients were divided into two groups (receiving either TOFO or ANA monotherapy) and observed for 12 weeks (observation points: 0 and 12 weeks). The TOFO and ANA groups were then further treated with ANA and TOFO, respectively, and the patients were observed for an additional 36 weeks (observation points: 24 and 48 weeks). Therapeutic effects and various biomarkers were compared between the two groups at the observation points.

Results: Combination therapy led to significant improvements in HbA1c levels and atherosclerosis markers. Additionally, the TOFO pretreatment group exhibited significant reductions in sLOX-1 and IL-6 levels.

Conclusion: The increase in sLOX-1 and IL-6 levels, which indicates the response of scavenger receptors to oxidized low-density lipoproteins in people with T2DM, is mitigated following TOFO and ANA combination therapy. TOFO alone or in combination with ANA may be beneficial for preventing atherosclerosis development in people with T2DM, in addition to its effect on improving HbA1c levels.

Cefepime is a fourth-generation cephalosporin utilized in treatment of multiple Gram-negative and -positive infections. The current report presents a case of 50-year-old man admitted with epidural abscess who developed neutropenia after prolonged use of cefepime. The neutropenia developed after 24 days of cefepime treatment and resolved 4 days after cessation of cefepime. Assessment of the patient's profile indicated no other possible cause for neutropenia. A literature review was done, and is presented herein to compare and identify the pattern of cefepime-induced neutropenia in 15 patients. The data presented in this article highlight that despite its rarity, cefepime-induced neutropenia should be considered by clinicians when planning a prolonged course of cefepime.

Introduction: Iberdomide, a novel cereblon modulator (CELMoD^®), is currently under clinical investigation for hematology indications. To evaluate the influence of hepatic impairment on the pharmacokinetics (PK) of iberdomide and its major active metabolite M12, a phase 1, multicenter, open-label study was conducted in healthy subjects and subjects with mild, moderate, and severe hepatic impairment.

Methods: Forty subjects were enrolled in the study and divided into five groups based on hepatic function. 1 mg iberdomide was administered and plasma samples were collected to evaluate the pharmacokinetics of iberdomide and M12.

Results: After a single dose of iberdomide (1 mg), mean iberdomide Cmax (maximum observed concentration) and AUC (area under the concentration-time curve) exposure were generally comparable between hepatic impairment (HI) subjects (severe, moderate and mild) and their respective matched normal controls. Mean Cmax and AUC exposure of the metabolite M12 were generally comparable between mild HI and matched normal subjects. However, mean Cmax of the M12 was 30% and 65% lower and AUC was 57% and 63% lower in moderate and severe HI subjects as compared to their respective matched normal controls. However, given the relatively low M12 exposure as compared to its parent drug, the observed differences were not considered clinically meaningful.

Conclusion: In summary, 1 mg single oral dose of iberdomide was generally well-tolerated. HI (mild, moderate or severe) had no clinically relevant impact on iberdomide PK and therefore, no dose adjustment is warranted.