Even though multiple factors are involved in the high fluctuation of voriconazole (VCZ) plasma concentration, little is known regarding the influence of proinflammatory cytokines on VCZ concentration. The aim of this study was to investigate the influence of proinflammatory cytokines, namely, interleukin (IL)‐1β, IL‐6, IL‐18, interferon‐γ, tumor necrosis factor‐α, and transforming growth factor (TGF)‐β1 on VCZ trough concentration (VCZ‐Cmin) in Chinese patients with different forms of hematologic disorders. A total of 250 plasma samples from 113 patients were analyzed for VCZ‐Cmin and proinflammatory cytokines using a validated liquid chromatography–tandem mass spectrometry and enzyme‐linked immunosorbent assay methods, respectively. Patient demographics and clinical characteristics were obtained from hospital records. VCZ‐Cmin was significantly correlated with IL‐18 in acute myeloid leukemia (r = 0.456; P ˂ .0001), acute lymphoblastic leukemia (r = 0.317; P = .019), and chronic myeloid leukemia (r = 0.737; P = .004) while VCZ‐Cmin and TGF‐β1 were correlated (r = 0.436; P ˂ .001) in acute myeloid leukemia patients only. VCZ‐Cmin at different concentration range showed significant inhibitory effect of IL‐6. A backward multiple linear regression model revealed patient age (coefficient [β] = 0.025; P = .04), gamma‐glutamyl transferase (β = 0.003; P = .023), IL‐6 (β = –0.001; P = .024), proton pump inhibitor coadministration (β = 1.518; P = .002), and cytochrome P450 (CYP) 2C19 polymorphism as predictors of VCZ‐Cmin; however, these factors explained only 29% of VCZ‐Cmin variation. In conclusion, IL‐18 and TGF‐β1 have correlation with VCZ‐Cmin in Chinese patients with leukemia. Apparently, VCZ may have an inhibitory effect on IL‐6 levels. Furthermore, patient age, gamma‐glutamyl transferase, IL‐6, PPI coadministration, and cytochrome P450 2C19 polymormorphism partially predicted the VCZ‐Cmin. Therapeutic drug monitoring of VCZ in Chinese patients is highly encouraged.

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Background: Several poly ADP ribose polymerase inhibitors (PARPis) are currently approved for the treatment of a variety of cancers. The safety profile of PARPis has not yet been systemically analyzed in the real world. We conducted this pharmacovigilance analysis using the US FDA’s Adverse Event Reporting System (FAERS) database to explore the difference in adverse events (AEs) among PARPis.Methods: FAERS data (December 2014 to October 2021) were searched for reports of all FDA-approved PARPis across all indications. We used the standardized MedDRA query (SMQ) generalized search AEs on the preferred term (PT) level based on case reports. After filtering duplicate reports, disproportionality analysis was used to detect safety signals by calculating reporting odds ratios (ROR). Reports were considered statistically significant if the 95% confidence interval did not contain the null value.Results: Within the standardized MedDRA queries, significant safety signals were found, including those for olaparib [blood premalignant disorders (ROR = 17.06)], rucaparib [taste and smell disorders (ROR = 9.17)], niraparib [hematopoietic throbocytopenia (ROR = 28.2)], and talazoparib [hematopoietic erythropenia (ROR = 9.38)]. For AEs on the PT level, we found several significant signals, including platelet count decreased with niraparib (ROR = 52.78); red blood cell count decreased with niraparib (ROR = 70.47) and rucaparib (ROR = 15.09); myelodysplastic syndrome with olaparib (ROR = 35.47); acute myeloid leukaemia with olaparib (ROR = 25.14); blood pressure fluctuation with niraparib (ROR = 20.54); lymphangioleiomyomatosis with niraparib (ROR = 471.20); photosensitivity reaction with niraparib (ROR = 21.77) and rucaparib (ROR = 18.92); renal impairment with rucaparib (ROR = 33.32); and interstitial lung disease with Olaparib (ROR = 11.31). All the detected safety signals were confirmed using signals of disproportionality reporting methods.Conclusion: PARPis differed in their safety profile reports. The analysis of the FAERS database revealed significant safety signals that matched previously published case reports, including serious gastrointestinal, blood and lymphatic system, cardiovascular and respiratory complications, which require individualized drug administration according to patients’ conditions.

Huperzine A is a potent, reversible, and blood-brain barrier permeable acetylcholinesterase inhibitor. The aim of this study was to compare the pharmacokinetics, tolerability, and bioavailability of two formulations with the established reference formulation of huperzine A in a fasting, healthy Chinese male population. This was a randomized, single-dose, 3-period, 6-sequence crossover study. The plasma concentrations of huperzine A were determined by liquid chromatography tandem mass spectrometry. Tolerability was assessed based on subject interview, vital sign monitoring, physical examination, and routine blood and urine tests. The mean (SD) pharmacokinetic parameters of the reference drug were C, 1.550 (0.528) ng/mL; t, 12.092 (1.898) h; AUC, 17.550 (3.794) ng·h/mL. Those of the test formulation A and test formulation B were C, 1.412 (0.467), 1.521 (0.608) ng/mL; t, 12.073 (2.068), 12.271 (1.678) h; AUC, 15.286 (3.434) ng·h/mL, 15.673 (3.586) ng·h/mL. The 90% confidence intervals for the AUC and C were between 0.80 and 1.25. No adverse events were reported by the subjects or found with results of clinical laboratory test. The test and reference products met the regulatory criteria for bioequivalence in these fasting, healthy Chinese male volunteers. All three formulations appeared to be well tolerated.