J Public Health Manag Pract. 2024 Sep-Oct 01;30:S116-S118. doi: 10.1097/PHH.0000000000001978. Epub 2024 Jul 22.

ABSTRACT

Pharmacist-led interventions are pivotal in identifying and resolving potential adverse drug events (pADEs) while enhancing blood pressure control and medication adherence through educational and counseling interventions. This practice brief outlines the outcomes of the Blue Bag Initiative (BBI), which enhanced pharmacist-led comprehensive medication reviews (CMRs) across community pharmacies in Virginia under Center for Disease Control Cooperative Agreement NU58DP006535. BBI yielded a rate of 131.6 pADEs identified per 100 participants and demonstrated cost savings of 1 to 3 million dollars for the health care system. This report underscores the significance of a standardized, pharmacist-led CMR as integral to interdisciplinary team-based care models within physician practices, facilitating medication therapy management implementation. Enhanced CMR can improve cardiovascular health outcomes while reducing health care expenditures by augmenting patient engagement and medication adherence. This study thus highlights the efficacy and potential of pharmacist-led interventions in increasing access to and optimizing patient care.

PMID:39041745 | DOI:10.1097/PHH.0000000000001978

Zhongguo Zhong Yao Za Zhi. 2024 Jun;49(12):3396-3403. doi: 10.19540/j.cnki.cjcmm.20240306.501.

ABSTRACT

This study utilized a prospective, large-sample, multi-center, and registered key specialty approach of hospitals to monitor the application of Reduning Injection. A total of 100 249 adolescent patients aged 14 years and below who received Reduning Injection were monitored, resulting in 83 cases of adverse events, with 76 of them being classified as adverse drug reaction(ADR). The calculated incidence rate of ADR for Reduning Injection was 0.076%, indicating a very rare ADR. The main symptoms of ADR were pruritus, diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsion, and chills. All ADR cases were reported for the first time, including three new ADR cases and 73 known ADR cases. The categories of ADR was general ADR. All ADR was mild in severity. There were more males than females in ADR patients. One patient had a history of ADR, and the drug causing ADR was buprofen. The largest number of ADR cases occurred when the dosage of Reduning injection was 5-10 mL. The dropping speed was 30 drops or less per min, and the solvent type was 5% glucose injection. The most common manifestation of ADR patients was pruritus, followed by diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsions, and chills. 72 patients(94.74% of ADR patients) discontinued the drug, and three patients(3.95% of ADR patients) were given oxygen inhalation. 47 cases(61.84% of ADR patients) were treated with medication, of which dexamethasone was the most used(24 cases, 46.15% of ADR patients). 76 ADR patients were cured or improved. ADRs are more likely to occur when diagnosed with acute bronchitis by western medicine and cough by traditional Chinese medicine(TCM), TCM syndrome type is wind heat syndrome, and the combination medicine is ambroxol hydrochloride and bromhexine hydrochloride injection, ascorbic acid/vitamin C injection. This result provides an evidence-based safety basis for active pharmacovigilance of Reduning Injection in adolescents aged 14 years and below.

PMID:39041103 | DOI:10.19540/j.cnki.cjcmm.20240306.501

Adv Ther. 2024 Jul 22. doi: 10.1007/s12325-024-02940-8. Online ahead of print.

ABSTRACT

INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening inflammatory skin disease. Interleukin (IL)-36 signalling may play a central role in GPP pathogenesis. Spesolimab is a humanized anti-IL-36 monoclonal antibody inhibiting the IL-36 signalling pathway. Here, we investigated the pharmacokinetics and safety of spesolimab in healthy Chinese subjects.

METHODS: In this Phase 1, single-dose, parallel-group, open-label study, healthy Chinese subjects aged 18-45 years received a single spesolimab dose by intravenous infusion (IV; 450 mg, 900 mg, or 1200 mg) or subcutaneous (SC) administration (300 mg or 600 mg). Primary endpoints were spesolimab exposure (area under the plasma concentration-time curve and maximum plasma concentration); secondary endpoints were treatment-emergent adverse events (TEAEs) and drug-related adverse events (AEs).

RESULTS: Fifty subjects received IV (n = 30) or SC (n = 20) spesolimab (n = 10 per dose group); 60.0% were male, mean ± standard deviation age was 31.5 ± 6.6 and 31.0 ± 6.5 years in the IV and SC groups, respectively. Spesolimab exposure increased in a dose-proportional manner in both groups. TEAEs were reported in 83.3% and 80.0% of subjects in the IV and SC groups, the most common TEAE was upper respiratory tract infection (20.0% and 25.0%, respectively). One serious AE of hand fracture was reported in the 900 mg IV group that was not considered drug-related. Drug-related AEs were reported in 53.3% and 55.0% of subjects in the IV and SC groups. All laboratory-related AEs were mild and resolved.

CONCLUSION: Spesolimab exposure increased in a dose-proportional manner after a single dose by IV and SC administration. Spesolimab was well tolerated in healthy Chinese subjects.

CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov registration: NCT04390568.

PMID:39039387 | DOI:10.1007/s12325-024-02940-8

Sci Rep. 2024 Jul 22;14(1):16821. doi: 10.1038/s41598-024-67263-8.

ABSTRACT

Reporting adverse drug reactions (ADRs) is fundamental in improving medication safety. Community pharmacists (CPs) being the first point of contact for individuals seeking healthcare in a community, play a significant role in ADR reporting. However, this has been poorly implemented in many countries including Nigeria. This paper aims to explore stakeholders' perspectives on current reporting practices and suggest ways to enhance ADR reporting among CPs in Nigeria. This qualitative study employed a purposive sampling approach to identify key informants. Key informant interviews (KIIs) were conducted with 25 carefully selected pharmacists, using a semi-structured interview guide between July 2023 and August 2023. The interview transcripts were analyzed using a thematic content approach. While a low ADR reporting trend was observed among all participating pharmacists, it was notably higher among those with less than five years of experience. The main barriers to ADR reporting, as identified by the interviewed community pharmacists were lack of awareness and knowledge, absence of motivation, and insufficient feedback from National Agency for Food Drug Administration and Control (NAFDAC). Training and awareness campaigns were the most frequently suggested methods for improving ADR reporting. Other proposed strategies included providing motivation, regular feedback, establishing mandatory reporting, and simplifying the reporting process. The study has highlighted the suboptimal ADR reporting practices among CPs in Anambra state. It underscores the significance of training, sensitization, advocacy, and other related interventions as pivotal means to enhance ADR reporting in this group. Furthermore, there is a pressing need for intervention-based studies to delve into and implement these approaches effectively.

PMID:39039143 | DOI:10.1038/s41598-024-67263-8

Drug Ther Bull. 2024 Jul 22:dtb-2024-000047. doi: 10.1136/dtb.2024.000047. Online ahead of print.

NO ABSTRACT

PMID:39038930 | DOI:10.1136/dtb.2024.000047

Drug Ther Bull. 2024 Jul 22:dtb-2024-000045. doi: 10.1136/dtb.2024.000045. Online ahead of print.

NO ABSTRACT

PMID:39038929 | DOI:10.1136/dtb.2024.000045

J Immunother Cancer. 2024 Jul 22;12(7):e009540. doi: 10.1136/jitc-2024-009540.

ABSTRACT

Immune checkpoint inhibitors (ICIs) have revolutionized oncology treatment. However, their success is mitigated by the recognition that ICI-induced immune-related adverse events (irAEs) pose considerable challenges to patients and clinicians. These autoimmune toxicities are heterogeneous, unpredictable, and reflect a disease state resulting from a change in the immune system of patients. This contrasts with the typical acute nature of toxicities from chemotherapy and molecularly targeted oncology therapies. Management is further complicated by the extended bioavailability of these agents in patients as well as the persistence of autoimmune pathology. Currently, irAE treatment remains suboptimal in many areas, as many expert guidelines remain vague on the optimal selection, dosing, and duration of steroids and the use of other immunosuppressive agents. This coupled with delays in diagnosis and difficulties for patients accessing effective irAE treatment results in barriers to effective irAE care. The latter is complicated by the lack of US Food and Drug Administration-approved irAE treatments that lead to insurance denials, as well as the high cost of biological immunosuppressant therapies. Fortunately, rheumatologists and other subspecialists with expertize in the management of chronic autoimmune conditions have become more involved in irAE diagnosis and management and may help navigate treatment. In this commentary, we discuss these issues and propose potential solutions to advance the field.

PMID:39038920 | DOI:10.1136/jitc-2024-009540

Cureus. 2024 Jun 18;16(6):e62641. doi: 10.7759/cureus.62641. eCollection 2024 Jun.

ABSTRACT

Rhabdomyolysis involves significant skeletal muscle injury and destruction, which can be triggered by trauma, intense physical activity, heat, prolonged immobility, certain medications, and endocrine disorders. Rhabdomyolysis in renal transplants can be more complicated, and the prognosis is not well known, especially in the context of coexisting rejection. We present a case of rifampicin-induced rhabdomyolysis with superimposed acute cellular rejection in a kidney transplant patient.

PMID:39036240 | PMC:PMC11258931 | DOI:10.7759/cureus.62641

Expert Rev Neurother. 2024 Jul 21:1-9. doi: 10.1080/14737175.2024.2382463. Online ahead of print.

ABSTRACT

INTRODUCTION: Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder characterized by tics. Pharmacotherapy is advised for patients whose symptoms affect their quality of life.

AREAS COVERED: The authors review the tic phenomenology and TS diagnostic criteria. The bulk of this article focuses on pharmacotherapeutic options for treating tics. They also highlight pharmacotherapies in the research pipeline.

EXPERT OPINION: Tic treatment must be tailored to individual needs. Behavioral therapy is the first line of treatment. Most with bothersome tics need pharmacotherapy and rarely, for medication-refractory cases, surgical therapy is indicated. Alpha-2 agonists are considered in patients with mild tics, especially in those with attention deficit with or without hyperactivity. Second-generation antipsychotics like aripiprazole and tiapride may be considered for severe tics. However, prescribers should be mindful of potential side effects, especially drug-induced movement disorders. Botulinum toxin injections may be considered for focal motor tics. Topiramate can be considered when other treatments are ineffective, and its benefits outweigh the risks. The same holds true for vesicular monoamine transporter-2 inhibitors, as they are deemed to be safe and effective in real-world use and open-label trials despite not meeting primary endpoints in placebo-controlled trials. Cannabinoids may be considered in adults if the approaches above do not control tics.

PMID:39034647 | DOI:10.1080/14737175.2024.2382463

Drug Ther Bull. 2024 Jul 20:dtb-2024-000046. doi: 10.1136/dtb.2024.000046. Online ahead of print.

NO ABSTRACT

PMID:39033017 | DOI:10.1136/dtb.2024.000046

J Clin Oncol. 2024 Jul 19:JCO2400272. doi: 10.1200/JCO.24.00272. Online ahead of print.

ABSTRACT

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In this analysis, we update our experience with the chemotherapy-free regimen of blinatumomab and ponatinib in 60 patients with newly diagnosed Philadelphia chromosome (Ph)-positive ALL. At a median follow-up of 24 months, the complete molecular response rate by reverse transcriptase-polymerase chain reaction was 83% (67% at the end of course one), and the rate of measurable residual disease negativity by next-generation clono-sequencing was 98% (45% at the end of course one). Only two patients underwent hematopoietic stem cell transplantation (HSCT). Seven patients relapsed: two with systemic disease, four with isolated CNS relapse, and one with extramedullary Ph-negative, CRLF2-positive pre-B ALL. The estimated 3-year overall survival rate was 91% and event-free survival rate was 77%. Three patients discontinued blinatumomab because of adverse events (related, n = 1; unrelated, n = 2) and nine discontinued ponatinib because of cerebrovascular ischemia, coronary artery stenosis, persistent rash, elevated liver function tests with drug-induced fatty liver, atrial thrombus, severe arterial occlusive disease of lower extremities, pleuro-pericardial effusion, and debilitation. In conclusion, the simultaneous combination of ponatinib and blinatumomab is a highly effective and relatively safe nonchemotherapy regimen. This regimen also reduces the need for intensive chemotherapy and HSCT in first remission in the majority of patients.

PMID:39028925 | DOI:10.1200/JCO.24.00272

J Chemother. 2024 Jul 19:1-5. doi: 10.1080/1120009X.2024.2379169. Online ahead of print.

ABSTRACT

Trastuzumab emtansine (T-DM1) is a targeted therapy combining trastuzumab and emtansine for human epidermal growth factor receptor 2(HER2)-positive breast cancer, with common side effects including fatigue, nausea, pain, headache, low platelet count, and elevated liver enzymes. Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterized by vascular malformations and telangiectasias in various organs. We present a case of a female patient with advanced breast cancer who developed HHT-like symptoms while on T-DM1 treatment. A 59-year-old woman treated with radiotherapy and T-DM1 every 21 days developed recurring nosebleeds and mucocutaneous and liver telangiectasias indistinguishable from HHT three months after receiving the first dose of T-DM1. Other organ vascular malformations were ruled out through screening protocols. The patient had no previous HHT symptoms or family history. Nasal care measures like lubrication and antifibrinolytics (tranexamic acid) were provided. In addition, propranolol was also prescribed due to its antiangiogenic and antitumoral properties, leading to significantly decreased epistaxis and telangiectasias. Microtubule disruptions caused by T-DM1, along with other angiogenic mechanisms may contribute to the development of telangiectasias resembling HHT. The use of propranolol, an initial approach for HHT, proved to be effective in this case. It is crucial for oncologists and HHT specialists to be aware of this rare adverse event associated with T-DM1 and to implement appropriate management strategies.

PMID:39028266 | DOI:10.1080/1120009X.2024.2379169

Trials. 2024 Jul 18;25(1):488. doi: 10.1186/s13063-024-08321-4.

ABSTRACT

BACKGROUND: Phase 1 clinical trials involve rigorous safety monitoring to identify any adverse effects of investigational treatments. There is growing evidence that healthy volunteers recruited in these studies may differ with respect to personality traits from the general population. This, in turn, may have a significant impact on the reporting of adverse events, particularly in trials investigating psychoactive treatments, including the psychedelic substances.

MAIN BODY: This analysis stems from our combined experience as investigators in phase 1 clinical trials and conveys an experiential understanding of the impact of psychological heterogeneity on study participation, reporting of adverse events and study outcomes.

CONCLUSION: Participant variability due to psychological characteristics is regularly overlooked in phase 1 clinical trials and may significantly impact on reporting of the adverse events. In our opinion, healthy volunteers who present for these studies should not only be defined by the absence of past or current medical and psychiatric illness but also characterised by their psychological attributes.

PMID:39026376 | DOI:10.1186/s13063-024-08321-4

Rev Mal Respir. 2024 Jul 17:S0761-8425(24)00234-1. doi: 10.1016/j.rmr.2024.06.008. Online ahead of print.

ABSTRACT

INTRODUCTION: Methotrexate (MTX) is a folate antagonist used as an immunosuppressant in a number of conditions, including rheumatoid arthritis (RA). Low-dose MTX (MTX-LD) is associated with a risk of haematological, hepatic, gastrointestinal and pulmonary toxicity, which may up until now have limited its use.

STATE OF THE ART: In RA, data from retrospective cohorts have reported a possible excess risk of methotrexate toxicity in cases of underlying interstitial lung disease (ILD). However, recent prospective and retrospective multicentre studies have found no such increased risk, and have reassuringly concluded that MTX-LD can be prescribed in cases of RA-associated ILD (RA-ILD).

PERSPECTIVES AND CONCLUSIONS: Current recommendations are not to delay the introduction of MTX in patients with RA at risk of developing ILD or in the presence of RA-ILD with mild to moderate respiratory impairment.

PMID:39025770 | DOI:10.1016/j.rmr.2024.06.008

Farm Hosp. 2024 Jul 17:S1130-6343(24)00094-1. doi: 10.1016/j.farma.2024.05.014. Online ahead of print.

ABSTRACT

INTRODUCTION: Intensive Care Units (ICUs) pose challenges in managing critically-ill patients with polypharmacy, potentially leading to Adverse Drug Reactions (ADRs), particularly in the elderly.

OBJECTIVE: To evaluate whether the severity and clinical prognosis scores used in ICUs correlate with the prediction of ADRs in aged patients admitted to an ICU.

METHODS: A cohort study was conducted in a Brazilian University Hospital ICU. APACHE II and SAPS 3 assessed clinical prognosis, while GerontoNet ADR Risk Score and BADRI evaluated ADR risk at ICU admission. Severity of the patients' clinical conditions was evaluated daily based on the SOFA score. Adverse Drug Reaction (ADR) screening was performed daily through the identification of ADR triggers.

RESULTS: 1295 triggers were identified (median 30 per patient, IQR = 28), with 15 suspected ADRs. No correlation was observed between patient severity and ADRs at admission (p=0.26), during hospitalization (p=0.91), or at follow-up (p=0.77). There was also no association between death and ADRs (p=0.28) or worse prognosis and ADRs (p>0.05). Higher BADRI scores correlated with more ADRs (p=0.001).

CONCLUSIONS: The data suggest that employing the severity and clinical prognosis scores used in Intensive Care Units is not sufficient to direct active pharmacovigilance efforts, which are therefore indicated for critically ill patients.

PMID:39025759 | DOI:10.1016/j.farma.2024.05.014

Clin Ther. 2024 Jul 17:S0149-2918(24)00143-7. doi: 10.1016/j.clinthera.2024.06.006. Online ahead of print.

ABSTRACT

PURPOSE: Doxecitine (deoxycytidine [dC]) and doxribtimine (deoxythymidine [dT]) powder for oral solution is a 1:1 mixture consisting of equal weights 2'-deoxycytidine (dC) and 2'-deoxythymidine (dT). Doxecitine and doxribtimine (referred to as study drug) is being developed as treatment for people with thymidine kinase 2 deficiency (TK2d). TK2d is an ultra-rare mitochondrial DNA depletion and multiple deletion syndrome characterized by progressive muscle weakness and premature death. Here, we report the pharmacokinetics (PK), the effect of food, and the tolerability of 2 study drug formulations, evaluated in 2 studies (Study MT-1621-103 and Study MT-1621-105).

METHODS: A sequential, ascending 1:1 dose ratio was used for both studies (n = 14 healthy volunteer adult participants/study). After a 28-day (Study MT-1621-103) or 35-day (Study MT-1621-105) screening period, participants fasted overnight and sequentially received 86.6, 173.4, and 266.6 mg/kg study drug with a 48-hour PK assessment period and 48-hour washout period between doses. After 48 additional hours, participants were fed a high-fat meal and received 266.6 mg/kg study drug. Plasma and urine were collected before dosing and throughout the 48-hour PK period. dC and dT concentrations were analyzed by validated liquid chromatography mass spectrometry methods. Safety was evaluated throughout the study and at 2-week follow-up.

FINDINGS: Plasma levels of dC and dT increased rapidly and dose-dependently above endogenous levels for both formulations, with a median Tmax of 1 to 2 hours under fasting conditions. Post-dose plasma dC and dT concentrations declined to nearly pre-dose (baseline) concentrations after 8 to 12 hours, suggesting rapid elimination. Peak and extent of plasma exposure (baseline-corrected Cmax and AUC0-t) tended to increase less than dose-proportionally for plasma dC and greater than dose-proportionally for plasma dT. PK variability of dC and dT was moderate-to-high (>30%). Administration with food delayed Tmax to a median of 2 to 4 hours and increased plasma exposure: baseline-corrected plasma dC Cmax and AUC0-t increased by ∼79% to 96% and 137% to 250%, respectively, and dT Cmax and AUC0-t increased by 27% to 29% and 74% to 89%, respectively, indicating a significant food effect. Renal clearance played a minor role in the elimination of systemically available intact dC and dT (Fe<0.3%). The study drug was generally well tolerated; most frequent study-drug-related adverse events (AEs) were diarrhea (n = 4/29, 14%) and dizziness (n = 3/29, 10%). Most AEs were mild-to-moderate in severity.

IMPLICATIONS: Doxecitine and doxribtimine are orally bioavailable in the intended clinical dose range. The PK profile supports a formulation consisting of equal doses of doxecitine and doxribtimine, a 3-times-daily dosing regimen, and administration with food.

PMID:39025716 | DOI:10.1016/j.clinthera.2024.06.006

Eur J Hosp Pharm. 2024 Jul 17:ejhpharm-2024-004205. doi: 10.1136/ejhpharm-2024-004205. Online ahead of print.

ABSTRACT

OBJECTIVES: Patients on oral anticancer therapy regularly experience medication-related problems (MRPs), potentially leading to non-adherence and medication waste. Most studies reporting these experiences have cross-sectional designs. The aim of our study was to explore patient reported MRPs, adherence and waste of oral anticancer medication over time.

METHODS: A prospective longitudinal quantitative interview study with 4 months follow-up was performed among patients on oral anticancer medication (mainly tyrosine kinase inhibitors, (anti)hormonal therapy, pyrimidine antagonists) using a semi-structured questionnaire. Patients from two Dutch university medical centres were included from March to December 2022 after informed consent was given. Four interviews were performed with 1 month in between. All interviews were audiotaped, after which the data were entered into an electronic case report form. The primary outcome was the mean number of MRPs per patient per interview round. Secondary outcomes were the proportion of patients with at least one MRP, types of MRPs, perceived non-adherence, medication waste (both in general and specifically for anticancer medication), costs of anticancer medication waste, and factors associated with medication waste as mentioned by the patient. Descriptive statistics were used to analyse the data.

RESULTS: Forty patients were included with a mean (SD) age of 64 (9) years; 43% were male. The mean number of MRPs per patient was 2.1 in the first interview and 1.2, 1.0 and 0.9 in the second, third and fourth interviews, respectively. Adverse drug reactions were the most frequently reported type of MRPs (30 (75%) patients in the first interview and 19 (65%) in the last interview). Unintentional non-adherence was regularly reported, especially in the first interview. Medication changes were frequent and associated medication waste was mentioned in all interviews.

CONCLUSIONS: Many patients using oral anticancer treatment report MRPs and this number remains substantial over time.

PMID:39019578 | DOI:10.1136/ejhpharm-2024-004205

Case Rep Gastroenterol. 2024 Jun 20;18(1):340-346. doi: 10.1159/000539439. eCollection 2024 Jan-Dec.

ABSTRACT

INTRODUCTION: Although terlipressin is known to cause bradycardia, this adverse effect is usually described in association with hypertension and is considered a benign compensatory response mediated by arterial baroreceptors. Cardiac monitoring for patients receiving terlipressin is not routinely recommended.

CASE PRESENTATION: A 77-year-old female patient with no history of coronary artery disease and no other coexisting risk factors for cardiac arrhythmias or conduction disturbances was admitted to intensive care unit with severe cholangitis, complicated by variceal bleeding. She developed severe sinus bradycardia following the use of terlipressin, which was associated with significant hypotension that required the infusion of norepinephrine. The bradycardia occurred again when terlipressin therapy was reattempted.

CONCLUSION: Vasopressin is known to sensitize baroreceptor reflexes by a central mechanism though its actions on V1a receptors in the area postrema, and we speculate that vasopressin analogues such as terlipressin may act in the same manner. That this effect is not widely described in terlipressin safety literature may be due to the overall younger age range of the trial population. This raises the possibility that cardiac monitoring may be warranted for elderly patients receiving terlipressin.

PMID:39015523 | PMC:PMC11250250 | DOI:10.1159/000539439

Front Pharmacol. 2024 Jun 25;15:1351871. doi: 10.3389/fphar.2024.1351871. eCollection 2024.

ABSTRACT

Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation. Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method. Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed. Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.

PMID:39015370 | PMC:PMC11250459 | DOI:10.3389/fphar.2024.1351871

Arch Clin Cases. 2024 Jul 16;11(2):69-73. doi: 10.22551/2024.43.1102.10291. eCollection 2024.

ABSTRACT

Patients with relapsing-remitting multiple sclerosis should be offered disease-modifying therapies as part of their management. Recommended options include integrin antagonist therapy including natalizumab as well as anti-CD20 monoclonal antibodies like, ocrelizumab, rituximab, ofatumumab, and ublituximab. These therapies reduce relapse rates and slow brain lesion accumulation. Disease-modifying therapies selection may depend on patient preferences, potential fetal harm, and specific drug risks, requiring continuous monitoring via tracking clinical relapses and new MRI brain lesions. Natalizumab carries a risk of progressive multifocal leukoencephalopathy, particularly in anti-JCV antibody-positive patients, necessitating regular monitoring. Ocrelizumab, rituximab, and ublituximab are associated with an increased risk of infections (especially respiratory and skin infections), infusion reactions, and hypogammaglobulinemia. Ocrelizumab additionally poses a heightened risk of immune-mediated colitis and breast cancer, and it is contraindicated for patients with active hepatitis B due to the risk of viral reactivation. Ublituximab has been noted to be linked to potential fetal harm. We report the case of a 42-year-old male with relapsing-remitting multiple sclerosis on ocrelizumab who developed persistent fever and shortness of breath, two weeks after his last ocrelizumab dose. Despite antibiotic treatment for suspected pneumonia, his symptoms persisted. A chest CT scan revealed multifocal ground-glass opacities suggestive of organizing pneumonia, likely secondary to ocrelizumab. The patient's condition improved with high-dose corticosteroids, underscoring the importance of vigilance for extremely rare ocrelizumab-associated pulmonary side effects and the need for prompt, appropriate intervention.

PMID:39015300 | PMC:PMC11250650 | DOI:10.22551/2024.43.1102.10291