International journal of clinical pharmacology and therapeutics最新文献

Objective: To investigate the differences and their clinical significance in the intestinal microbiota in patients with Parkinson's disease (PD) in comparison to those in healthy controls.

Materials and methods: 20 patients with PD who received treatment in the First Affiliated Hospital of Bengbu Medical College between January 2019 and December 2019 were selected as the research subjects to form the PD group, while 20 age- and gender-matched healthy volunteers were selected as the control group. Fecal samples from the two groups were collected, and the V4 region of 16S-ribosomal ribonucleic acid was selected for high-throughput sequencing analysis to explore any differences, as well as their significance, in the intestinal microbiota abundance at the class, family, and genus levels between the two study groups.

Results: The operational taxonomic unit cluster analysis revealed a high degree of overlap between the patients with PD and the controls. Compared with the controls, the relative abundance of Coriobacteriia and Coriobacteriaceae was increased in the PD group (p < 0.01), while the relative abundance of Lachnospiraceae was significantly lower (p < 0.01). The relative abundance of Collinsella, Escherichia, and Fusobacterium in the PD group was significantly higher than in the control group (p < 0.05).

Conclusion: Compared with the healthy subjects, the abundance of specific microflora was significantly different in the PD patients at the class, family, and genus level. Intestinal flora may act as a potential biomarker for PD and provide a theoretical basis for microflora transplantation therapy.

Objective: This retrospective analysis was to examine the efficacy and safety of belimumab in lupus nephritis in China.

Materials and methods: 25 patients who were regularly followed up every 3 months in our hospital in China were included. All patients were diagnosed as having lupus nephritis and received belimumab to complement standard therapy. The primary outcomes 24-hour proteinuria, complement level, estimated glomerular filtration rate (eGFR), SELENA-SLEDAI scores, prednisone daily dose, and adverse reactions were recorded at 12, 24, 36, and 48 weeks.

Results: The SELENA-SLEDAI scores and 24-hour urine protein of the 25 patients decreased visibly from baseline 15.96 ± 3.02, 1.52 ± 1.72 to 9.52 ± 2.66 (p < 0.01), 0.5 ± 0.2 (p < 0.05) at 48 weeks, the eGFR of the 25 patients increased from 76.45 ± 22.2 to 85.48 ± 19.26 (p < 0.01) at 48 weeks, complement levels also showed a trend to increase. One patient experienced renal flare at 48 weeks, and the level of the patient's 24-hour proteinuria had been > 0.7 g at 6 months; this may be a strong predictive factor for further renal response at 12 months. Belimumab added to the standard therapy also improved the hematologic complications caused by systemic lupus erythematosus in 2 patients with a lower glucocorticoid dose. There were no serious adverse events.

Conclusion: Belimumab may be effective and safe in lupus nephritis even with regard to hematologic complications.

Aims: The aims of this study were to evaluate and compare the pharmacokinetic profiles and bioequivalence of two tablet formulations of methylprednisolone (test formulation: Zhejiang Xianju Pharmaceutical Co., Ltd., China; reference formulation: Medrol, Pfizer Italia SRL) in healthy Chinese subjects under fasting and fed conditions.

Materials and methods: Subjects were randomly allocated to either the fasting group or the fed group and also to one of two sequences (test-reference or reference-test), according to which they received a single 16-mg dose of the test or reference methylprednisolone tablet in the study periods. Blood samples were collected pre dose and at intervals up to 16 hours after administration. Plasma methylprednisolone concentrations were determined using a validated liquid chromatography tandem mass spectrometry method. The safety of the medications was monitored throughout the study. The primary pharmacokinetic parameters measured were C_max, AUC_0-t, and AUC_0-∞.

Results: A total of 56 subjects were enrolled, and all completed the study. The 90% confidence intervals for C_max, AUC_0-t, and AUC_0-∞, measured under both fasting and fed conditions, fell within the acceptable range for bioequivalence of 80 - 125%. Analysis of variance showed that there were no significant differences in the primary pharmacokinetic parameters (C_max, AUC_0-t, and AUC_0-∞) between the test and reference formulation measured under both fasted and fed conditions. No serious or unexpected adverse drug reactions occurred during the study period.

Conclusion: The test methylprednisolone 16 mg tablet produced in China is bioequivalent to the reference formulation (Medrol) in healthy Chinese subjects measured under both fasting and fed conditions. Both formulations were well tolerated by all study participants.

Background: Whether the clinical pharmacist services (CPS) improve ICU physicians' compliance with venous thromboembolism (VTE) prophylaxis guidelines remains unclear, and the impact of CPS on VTE incidence and mortality in ICU patients should also be investigated.

Materials and methods: ICU patients were assigned to a CPS group or a control group according to the medical arrangements of the day of patient admission, without any intervention. The impact of CPS on guideline compliance, VTE incidence, and mortality was assessed.

Results: A total of 338 patients were included. With CPS, ICU physicians' compliance with VTE prophylaxis guideline was improved by 7 - 25% (p < 0.001). The incidences of VTE (9 vs. 17%, p = 0.037) and bleeding events (5 vs. 11%, p = 0.042) were both lower in the CPS group than in the control group. Multivariate Cox regression model showed that CPS was an independent risk factor for VTE events (HR = 0.438, 95% CI = 0.224 - 0.857, p = 0.016) and 14-day mortality (HR = 0.416, 95%CI = 0.25 - 0.692, p = 0.001).

Conclusion: CPS could significantly improve ICU physician compliance with VTE prophylaxis guidelines and reduce the incidence of VTE events and mortality in ICU patients. A clinical pharmacist should be involved in the daily management of ICU patients as an important member of the clinical team.

Objective: To identify the trends in tolvaptan prescription and the association between aging and tolvaptan-induced hypernatremia.

Materials and methods: A health insurance claims database and a spontaneous adverse drug reaction database were used.

Results: Of all patients who had been prescribed tolvaptan, the proportion of patients aged 60 - 79 years and ≥ 80 years was consistent at ~ 40%. Moreover, the prescription frequency of tolvaptan increased over time for patients in the same age groups. The adjusted reporting odds ratio of tolvaptan-induced hypernatremia was 5.54 (95% confidence interval, 3.31 - 9.25) in patients aged ≥ 60 years from among all patients and 2.09 (95% confidence interval, 1.59 - 2.75) in those aged ≥ 80 years from among those aged ≥ 60 years.

Conclusion: It may be necessary to be aware of hypernatremia in elderly patients who are expected to have increased prescriptions of tolvaptan.

Objective: Fractures are significantly associated with increased morbidity and mortality in older individuals; additionally, patients with diabetes mellitus are highly prone to fractures. The aim of the present study was to examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitor use and the risk of fracture in older patients by analyzing data obtained from spontaneous adverse event reporting databases from the United States and Japan.

Materials and methods: Data on older patients registered in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2013 to the end of 2019 and data registered in the Japanese Adverse Drug Event Report database (JADER) from April 2004 to December 2019 were used. Reporting odds ratio (ROR) and information component (IC) values were used for disproportionality analysis.

Results: Significant inverse associations between DPP-4 inhibitor use and fracture were found for DPP-4 inhibitors as a whole (ROR = 0.80; 95% CI = 0.73 - 0.88; IC = -0.31, 95% CI = -0.46 to -0.17); linagliptin (ROR = 0.74; 95% CI = 0.59 - 0.94; IC = -0.42, 95% CI = -0.75 to -0.08); and sitagliptin (ROR = 0.77; 95% CI = 0.68 - 0.88; IC = -0.36, 95% CI = -0.55 to -0.17) in the analyses of FAERS data. Similarly, significant inverse associations were also found for DPP-4 inhibitors as whole (ROR = 0.71; 95% CI = 0.59 to 0.86; IC = -0.46, 95% CI = -0.74 to -0.18); sitagliptin (ROR = 0.70; 95% CI = 0.52 - 0.95; IC = -0.49, 95% CI = -0.93 to -0.05); and vildagliptin (ROR = 0.54; 95% CI = 0.35 - 0.83; IC = -0.85, 95% CI = -1.49 to -0.22) in the analyses of JADER data.

Conclusion: Our analysis of adverse event databases using different algorithms revealed that DPP-4 inhibitor use was inversely associated with fracture in older patients.

Objective: To investigate the association between polymorphisms in the SLC22A2 gene and the hematological toxicity of oxaliplatin in colorectal cancer (CRC) patients receiving chemotherapy.

Materials and methods: A total of 81 patients with colon or rectal cancer were included in the study. The single nucleotide polymorphisms (SNPs) rs3127573, rs316019, and rs1869641 of the SLC22A2 gene were selected for genotyping using the polymerase chain reaction (PCR) and sequence analysis. Oxaliplatin-associated hematological toxicities were evaluated using the Common Toxicity Criteria for Adverse Events (CTCAE, Version 5.0).

Results: The rs1869641 genotype was significantly associated with the occurrence of thrombocytopenia (p = 0.047), whereas the rs316019 genotype was significantly associated with severity of leucopenia and neutropenia (p = 0.004 and 0.001, respectively). The rs3127573 genotype was not associated with hematological toxicities arising during chemotherapy with oxaliplatin.

Conclusion: It is shown here, for the first time, that the rs316019 gene variant of the SLC22A2 gene may be associated with the hematological toxicity of oxaliplatin. Patients with genotype CA/AA of rs316019 are more likely to develop serious hematological adverse effects.

Background: Improper prescriptions can cause adverse reactions in patients with chronic kidney disease (CKD).

Materials and methods: Hospital pharmacists investigated improper prescriptions, prerenal acute kidney injury (AKI) prescriptions, and adverse effects in AKI in 199 CKD patients at Kouseikai Hospital from July 2020 to June 2021, as well as combinations of "triple whammy" drugs (renin-angiotensin-system inhibitors, diuretics, and non-steroidal anti-inflammatory drugs) plus active vitamin D preparations. All participants (average age, 73.6 ± 16.2 years) were residents of Nagasaki City or its suburbs.

Results: Adverse reactions occurred in 38 of the 199 patients (19.1%). 13 patients had AKI, and 9 of these cases developed during the summer. A comparison of the 38 patients in the adverse reaction group and the 161 patients in the non-occurrence group showed that the former group was significantly older and had a lower body weight. In terms of renal function, estimated glomerular filtration rate (mL/min/1.73m²) was significantly lower, blood urea nitrogen/serum creatinine (BUN/S-Cr) was higher, dehydration was involved, and active vitamin D preparations were significantly more common in the adverse reaction group.

Conclusion: Our findings suggest that concomitant prescription of active vitamin D in combination with the drugs that constitute the triple whammy should be avoided. The absence of hypercalcemia should be confirmed and adequate fluid intake should be encouraged to prevent prerenal nephropathy.

Objective: Theracurmin, which contains the curcumin composition, CR-033P, has been demonstrated to be highly bioavailable. To compare the pharmacokinetics of the three compositions, CR-033P, CR-043P using modified starch as an alternative to the dispersant gum ghatti used in the CR-033P, and TS-P1 containing the newly developed amorphous curcumin, a randomized double-blind crossover study (3-way, 3-period) was conducted.

Materials and methods: A single dose of the curcumin capsules (TS-P1 45 mg, CR-033P 90 mg, and CR-043P 90 mg) was administered to healthy adult participants. Blood sampling was performed 24 hours after capsule administration, and the plasma concentration of total curcumin was determined using high-performance liquid chromatography coupled with tandem mass spectrometry.

Results: TS-P1 and CR-043P tended to have a slightly lower area under the concentration time curve (AUC) _0-24h than CR-033P, while TS-P1 displayed bioequivalence to CR-043P. Further, TS-P1 displayed bioequivalence to CR-033P in terms of AUC_0-12h, while that of CR-043P tended to be lower than that of CR-033P. TS-P1 had a higher AUC_0-12h than CR-043P. A statistically significant difference (p < 0.001) was found between the preparations in terms of C_max. TS-P1 tended to have a higher C_max than CR-033P, CR-043P tended to have a slightly lower C_max than CR-033P, and TS-P1 tended to have a higher C_max than CR-043P.

Conclusion: The newly developed TS-P1 composition seemed to display similar curcumin systemic exposure except for a higher plasma concentration than the CR-033P composition. Further, only a few significant differences were found between CR-043P and CR-033P.

Acetaminophen is generally regarded as a safe antipyretic and analgetic agent and is widely used in cases of pregnancy. However, acetaminophen is also one of the most frequently reported medications in cases of drug overdose. On the other hand, in the few instances described in the literature, where normal doses of acetaminophen administered during pregnancy may have had a fatal outcome, evidence existed pointing to a history of liver disease. It is therefore of interest that the patient in this report who died of liver failure after ingesting standard doses of acetaminophen also suffered from intrahepatic cholestasis during pregnancy although there was no history of liver disease. Other than these instances, there have been no previous reports in the literature of a normal, therapeutic dose of acetaminophen having a fatal outcome in pregnancy. This case emphasizes the need for caution when prescribing acetaminophen during pregnancy to patients with a history of liver disease, regardless of whether the liver function has returned to normal.