Gu N, et al. Transl Clin Pharmacol. 2020 Mar;28(1):17-33. https://doi.org/10.12793/tcp.2020.28.e4

Although uric acid-lowering agents such as xanthine oxidase inhibitors have potential cardioprotective effects, studies on their use in preventing cardiovascular diseases are lacking. We investigated the genetically proxied effects of reducing uric acid on ischemic cardiovascular diseases in a lipid-level-stratified population. We performed drug-target Mendelian randomization (MR) analyses using UK Biobank data to select genetic instruments within a uric acid-lowering gene, xanthine dehydrogenase (XDH), and construct genetic scores. For nonlinear MR analyses, individuals were stratified by lipid level. Outcomes included acute myocardial infarction (AMI), ischemic heart disease, cerebral infarction, transient cerebral ischemic attack, overall ischemic disease, and gout. We included 474,983 non-gout individuals with XDH-associated single-nucleotide polymorphisms. The XDH-variant-induced uric acid reduction was associated with reduced risk of gout (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.78–0.93; P < 0.001), cerebral infarction (OR, 0.86; 95% CI, 0.75–0.98; P = 0.023), AMI (OR, 0.79; 95% CI, 0.66–0.94; P = 0.010) in individuals with triglycerides ≥ 188.00 mg/dL, and cerebral infarction in individuals with low-density lipoprotein cholesterol (LDL-C) ≤ 112.30 mg/dL (OR, 0.76; 95% CI, 0.61–0.96; P = 0.020) or LDL-C of 136.90–157.40 mg/dL (OR, 0.67; 95% CI, 0.49–0.92; P = 0.012). XDH-variant-induced uric acid reduction lowers the risk of gout, AMI for individuals with high triglycerides, and cerebral infarction except for individuals with high LDL-C, highlighting the potential heterogeneity in the protective effects of xanthine oxidase inhibitors for treating AMI and cerebral infarction depending on the lipid profiles.

Suh HJ, et al. Infect Chemother. 2017 Jun;49(2):135-139. https://doi.org/10.3947/ic.2017.49.2.135

Vancomycin, a first-line drug for treating methicillin-resistant Staphylococcus aureus infections, is associated with acute kidney injury (AKI). This study involved an evaluation of biomarkers for AKI detection and their comparison with traditional serum creatinine (SCr). We prospectively enrolled patients scheduled to receive intravenous vancomycin for methicillin-resistant S aureus infection. Blood samples for pharmacokinetic assessment and SCr and cystatin C (CysC) measurements were collected at baseline and on days 3, 7, and 10 from the initiation of vancomycin administration (day 1). Urinary biomarkers, including kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin, and clusterin, were collected from days 1 to 7 and adjusted for urinary creatinine levels. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Of the 42 patients, 6 experienced vancomycin-induced AKI. On day 7, the change from baseline eGFR using CysC (ΔeGFR_CysC) showed a stronger correlation with vancomycin area under the curve (r = −0.634, P < .001) than that using SCr (ΔeGFR_SCr; r = −0.437, P = .020). ΔeGFR_SCr showed no significant correlation with vancomycin pharmacokinetic in patients with body mass index ≥23. The median (interquartile range) level of KIM-1 (μg/mg) was significantly higher in the AKI group (0.006 [0.005–0.008]) than in the non-AKI group (0.004 [0.001–0.005]) (P = .039, Mann–Whitney U test), with area under the receiver operating characteristic curve (95% confidence interval) of 0.788 (0.587–0.990). Serum CysC, particularly in overweight individuals or those with obesity, along with urinary KIM-1 are important predictors of vancomycin-induced AKI. These results may aid in selecting better biomarkers than traditional SCr for detecting vancomycin-induced AKI.

Kim TE, et al. Transl Clin Pharmacol. 2022 Sep;30(3):121-128. https://doi.org/10.12793/tcp.2022.30.e14

There is a lack of studies on the effects of Korean ginseng ( Panax ginseng C.A. Meyer) on face or body temperature. Therefore, in this study, we evaluated the effects of a black ginseng extract, KGR-BG1, on head and face temperatures and compared them with those of red ginseng extract and a placebo. We assessed their safety and tolerability and examined changes in the serum levels of biomarkers associated with immune responses, as well as with glucose and lipid metabolism. A randomized, double-blind, placebo-controlled study was conducted with 180 participants. The participants were randomly assigned to the KGR-BG1, red ginseng extract, or placebo group. Each group received a 1500 mg oral dose of their respective substances containing 1000 mg of the active component or placebo twice daily for 6 weeks. After treatment, changes in the head, face, and body temperature were measured, and serum biomarkers were evaluated. A total of 172 participants completed the evaluation after 6 weeks of treatment. No significant differences were observed in the head, face, and body temperatures among the treatment groups. After 6 weeks of treatment, the serum levels of biomarkers associated with inflammation, glucose metabolism, and lipid metabolism were similar to the baseline levels in all treatment groups. KGR-BG1 was well-tolerated compared with red ginseng extract and placebo. KGR-BG1 did not significantly alter head, face, or body temperature, or serum biomarker levels, and it was well tolerated in healthy volunteers over 6 weeks of treatment. Study Registration: Registered at Clinical Research Information Service (CRIS; https://cris.nih.go.kr ) as KCT0003126.