Journal of Clinical Pharmacy and Therapeutics最新文献

What is Known and Objective. Voriconazole (VRC) increases the blood concentration of Tacrolimus (TAC). However, the patterns of changes in TAC trough concentration (TAC C0) and dose-adjustment regimens after VRC discontinuation have not been reported. We aimed to explore the changing pattern of TAC C0 after VRC discontinuation and provide strategies for TAC dose adjustment and blood concentration monitoring in renal transplant recipients. Methods. The clinical data of 46 renal transplant patients pre- and during VRC medication and VRC discontinuation were retrospectively recorded, including doses and concentrations ₀ of TAC and VRC; biochemical indicators such as liver and kidney function; and CYP3A5, CYP3A4, and CYP2C19 gene types. Results and Discussion. After discontinuing VRC for 2–4 days, 81% of the patients returned to their initial TAC dose, although TAC C₀ and TAC dose-adjusted trough concentration (C/D) were 2.43-fold and 3.35-fold higher, respectively, than pre-VRC administration. After 5–7 days, TAC C₀ and C/D gradually recovered. TAC C/D was significantly higher after VRC discontinuation when the VRC trough concentration (VRC C0) was greater than 2.43 mg/L; CYP3A5, CYP3A4, and CYP2C19 genotypes and the administration of erythromycin did not affect the change in TAC C/D. What is New and Conclusion. TAC C/D remains elevated 2–4 days after discontinuing VRC compared to pre-VRC administration, with gradual recovery observed 5–7 days after VRC discontinuation. To avoid excessive blood TAC C0 , the initial TAC dose should not be immediately reinstated upon VRC discontinuation for 2–4 days. VRC C₀ are a critical factor influencing the change in TAC C/D ratio after VRC discontinuation.

Aims. The aim of this study was to confirm the repairing effect of ginsenoside Rb1 (GS-Rb1) on mechanical trauma to periurethral tissues caused by childbirth and to explore its potential preventive mechanisms for mechanical trauma-induced stress urinary incontinence. Methods. 48 healthy adult female Sprague–Dawley (SD) rats were randomly divided into four groups: normal control, SUI groups, L-GS-Rb1 groups, and H-GS-Rb1 groups, with 12 rats in each group. The histopathological examinations of the urethral were performed to detect the morphological changes after repair of periurethral traumatic tissue. The TGF-β1/Smad and NRF2/ARE signaling pathways related to periurethral tissue trauma repair were determined by RT-PCR and western blot. The bladder capacity and LPP were examined in rats. Results. GS-Rb1 significantly decreased the number of fragmented and disorganized elastic and muscle fibers in the urethra and anterior vaginal wall of SUI rats. GS-Rb1 also increased the collagen content and reduced damage to the structural integrity of the periurethral myofibers. Furthermore, GS-Rb1 promoted expressions of TGF-β1, Smad2, Smad3, Smad7, p-Smad3, p-Smad2, and collagens I and III. It also increased the protein levels of Nrf2, GPX1, and MnSOD. The bladder capacity and LPP of rats in the L-GS-Rb1 group were close to those of rats in the normal groups. Conclusions. Ginsenoside Rb1 promotes the repair of periurethral tissue trauma in the postpartum period and has a preventive effect on the occurrence of stress urinary incontinence.

Objective. This study aimed to explore the therapeutic targets and related pathways of Kuntai capsules (KTCs) for premature ovarian insufficiency (POI) using network pharmacology and molecular docking. Methods. The active components and their targets of KTCs were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) website, and disease therapeutic targets of POI were downloaded from DisGeNET, GeneCards, and OMIM databases and combined with the disease differential genes of POI microarray dataset from the Gene Expression Omnibus (GEO) database. The intersecting genes of drug potential therapeutic targets and disease therapeutic targets were uploaded to the STRING database to form a protein-protein interaction network. Also, the possible pathway of KTCs in the treatment of POI was explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis; through the core therapeutic targets, the corresponding active ingredients of KTCs were found. Finally molecular docking was conducted to verify the accuracy of the drug action. Results. 120 potential therapeutic targets of KTCs for POI were found. The bioinformatics analysis revealed that KTCs may regulate the recruitment, growth, and development of follicles by controlling various pathways such as fluid shear stress, atherosclerosis, PI3K/AKT, and p53 signaling. They can inhibit granulosa cell atrophy and apoptosis, promote follicle maturation, regulate follicle sensitivity to follicle-stimulating hormone, and ultimately impact ovarian function. The core therapeutic targets were TP53, AKT1, and TNF, and the corresponding active ingredients were quercetin, kaempferol, and stigmasterol. The molecular docking results showed that all the root mean square deviations were less than 2. Conclusions. KTCs improve ovarian function probably by acting on regulating the recruitment of follicles, reducing the apoptosis of granulosa cells, promoting their growth and development, reducing oxidative stress damage, and improving the sensitivity of follicles to FSH.

Objectives. This study aimed to investigate the effects of different triazole antifungal agents on the blood concentration and dosage of cyclosporine (CsA) in patients with aplastic anaemia (AA). Methods. This retrospective study enrolled AA patients who received CsA and triazole antifungal agents simultaneously between January 2018 and December 2022. The ratio of CsA blood concentration (ng/mL) to dosage (mg/day) (C/D) co-administration with and without azoles was compared. The effects of different triazole antifungal agents on blood concentrations and dosages of CsA were analysed. Results. The mean C/D ratio of CsA increased 1.97 times when co-administered with posaconazole (POS), while the mean C/D ratio of CsA increased 1.76 times when co-administered with fluconazole (FCZ). Compared with CsA monotherapy, there was a significant difference in CsA concentrations among patients with azoles (P < 0.05). The mean dose of CsA decreased was 0.26 (−0.25—1.05) mg/kg/day and 0.18 (−0.50—0.69) mg/kg/day when co-administered with POS and FCZ, respectively. There is a wide interindividual variability in the magnitude of drug interaction between azoles and CsA. Conclusions. Although azoles increased CsA concentration, a wide individual variability was found in the patients with CsA C/D ratio. Therefore, the CsA dose should be adjusted by closely monitoring the blood levels of CsA co-administered with triazole antifungal agents. In addition, we observed that POS had a greater effect on the blood concentration of CsA than FCZ. When adjusting the dose of CsA in clinical practice, the blood concentration of CsA and the type of co-administered triazole antifungal agents should be considered.

Background. Rheumatoid arthritis (RA) is an inflammatory condition that causes joint damage and is associated with pain. The biological disease-modifying antirheumatic drugs (bDMARDs) for RA are linked to additional therapeutic benefits as they suppress the inflammatory process, which in turn prevents joint erosion and reduces pain. Thus, the use of bDMARDs has the potential to reduce the need for other analgesic and anti-inflammatory therapies for RA. The aim of this study was to examine the analgesic and anti-inflammatory use around the initiation of bDMARDs. Methods. A cohort study was conducted using a 10% random sample of the population dispensing medicines under the Australian Pharmaceutical Benefits Scheme. People who initiated the first bDMARD for RA between 2014 and 2018 were included. The proportion who received any analgesic or anti-inflammatory, including nonsteroidal anti-inflammatory drugs, opioids, or glucocorticoids, in the twelve months prior to and post-bDMARD initiation was determined and compared using regression models. Results. There were 18,360 persons in the cohort, with a mean age of 55 years, and 69% were women. The use of any analgesic or anti-inflammatory in both tumor necrosis factor inhibitor (TNFi) and non-TNF initiators increased prior to initiation of bDMARD–from 43% to 52% in TNFi and from 52% to 63% in non-TNF initiators. In both groups, overall use decreased significantly post initiation to 37% and 42% in TNFi and non-TNF initiators, respectively (p < 0.0001). bDMARD initiation was associated with lower use of glucocorticoid therapy, but there was no decreasing effect on opioid use. Conclusion. While the use of any analgesic or anti-inflammatories decreased post-initiation of bDMARDs for RA, more than one-third of people were dispensed analgesic or anti-inflammatory agents twelve months post initiation. Ongoing review of the need for analgesic and glucocorticoids appears warranted, with assessment of nonpharmacological approaches to support pain management.

Background. Globally, ovarian cancer is a leading contributor to cancer-related fatalities among women, with a notable concern being the occurrence of liver metastasis as a prevalent clinical complication. This study aims to investigate the potential impact of alpha kinase 2 (ALPK2) on ovarian cancer liver metastasis (OCLM), assessing its implications for patient prognosis and tumor advancement. Our research seeks to examine the prognostic significance of ALPK2 in individuals with OCLM and unravel the consequences of ALPK2 knockdown on the proliferation and invasion of ovarian cancer cells. Methods. A retrospective analysis of 49 OCLM cases from our medical center was conducted to evaluate the prognostic significance of ALPK2 through survival analyses. Experimental investigations involved the use of shRNA to knock down ALPK2 in ovarian cancer cell lines, with subsequent scrutiny of cellular changes. Results. Survival analyses revealed that ALPK2 functions as an independent adverse prognostic factor in OCLM (HR = 3.74, 95% CI: 1.34–10.42, and P = 0.012). Knockdown experiments indicated a reduction in cell proliferation and invasion capacities, potentially associated with the epithelial-mesenchymal transition process. Conclusions. ALPK2 emerges as a crucial oncogene promoting tumors in OCLM. Its knockdown exhibits significant therapeutic potential by hindering cancer progression. Further investigations could solidify the role and therapeutic possibilities of ALPK2 in the treatment of ovarian cancer, particularly in cases involving liver metastasis.

Background. Management of diabetic neuropathy (DN) is a challenging issue. Therefore, integration of pharmaceutical care provided by the clinical pharmacists with pharmacotherapy may provide multifaceted approach to target the management of hyperglycemia and diabetic neuropathic complication. This study aimed to evaluate the effects of resveratrol (Resv) and/or pharmaceutical care (PC) on glycemic control and amelioration of diabetes-associated neuropathic complications. Patients and Methods. A four-arm randomized placebo-controlled clinical trial assigned 120 patients from the Diabetes and Endocrinology Center in Sulaymaniyah City, Iraq. The patients were divided into four groups. The Resv group (n = 30) received 500 mg Resv capsules once daily. The Placebo group (n = 30) received placebo capsules. Resv + PC (n = 30) received Resv 500 mg capsules with PC. Placebo + PC (n = 30) received placebo capsule plus PC. The duration of the intervention was 90 days. Drug therapy problems (DTPs) have been utilized as an important domain in PC. Clinical signs, symptoms, and neuropathic abnormalities were assessed using the Michigan Neuropathy Screening Instrument (MNSI), Douleur Neuropathique 4 (DN4) questions, and nerve conduction studies (NCSs) of the lower-limb sensory and motor nerves. Results. 97 patients from all the groups completed the study. At baseline, 84% of the Resv, 87% of the Placebo, and 92% of each of Resv + PC and Placebo + PC groups, respectively, had at least one DTP. The provision of PC resulted in a dramatic reduction in the number of DTP. Resveratrol with PC significantly ameliorated hyperglycemic status, neuropathic signs, and symptoms, as evidenced by a decrease in MNSI and DN4 scores and improvement in electroneurographic parameters. Conclusion. These findings support the integration of the PC concept into a pharmacotherapy intervention; they also encourage supplementation of Resv with conventional diabetes therapy to emphasize on the importance of this herbal medicine with the provision of PC in the management of diabetes and its neuropathic complications. This trial is registered with NCT05172947.

What Is Known? and Objective. Ceftriaxone has been widely used to treat bacterial meningitis in pediatric patients. Ceftriaxone dosing regimens of 80–120 mg/kg/day have been recommended for bacterial meningitis in pediatric patients, and the usual duration of therapy is 7–14 days. Although the target site for meningitis is cerebrospinal fluid (CSF), a CSF pharmacokinetic (PK) model in pediatric patients has not been reported. We aimed to develop a CSF PK model of ceftriaxone, using not only serum but also CSF concentration data, and to evaluate the appropriateness of dosing regimens for pediatric patients with bacterial meningitis. Methods. The population PK model was developed by simultaneously fitting serum and CSF data from pediatric patients described in nine published articles. Probabilities of attaining a pharmacodynamic target (100% T > MIC, 100% of time that drug concentrations above the minimum inhibitory concentration) in CSF were estimated for some dosing regimens. Results and Discussion. Twenty-four pediatric patients with meningitis were the subjects for PK modeling (0.52–13 years old, and 3.5–50 kg of body weight). Sixty-eight serum concentrations and 98 CSF samples were used to develop the CSF PK model. The CSF/serum concentration ratio at the same sampling time was 0.0628 ± 0.0689. Age was not a statistically significant covariate in the PK parameter. In the CSF PK model, 40–60 mg/kg q12 h achieved a target attainment probability >90% against causative bacteria for bacterial meningitis. However, 4-h infusion (rather than 0.5-h infusion) dosing regimens were required for efficacy against antimicrobial-resistant bacteria with high MICs. What Is New? and Conclusion. Ceftriaxone-dosing regimens with prolonged infusion times might be reasonably effective for treating antimicrobial-resistant pathogens in empiric therapy.