Reduced blood glucose levels by the combination of vadadustat in an elderly patient with chronic kidney disease who was receiving mitiglinide and sitagliptin: a case report.

BACKGROUND: Our case is the first report showing the development of hypoglycemia following the administration of vadadustat in a patient with chronic kidney disease being treated with mitiglinide and sitagliptin, possibly due to drug-drug interaction between vadadustat and sitagliptin under the administration of mitiglinide. CASE PRESENTATION: A 72-year-old man with type 2 diabetes mellitus had received sitagliptin 50 mg once daily and mitiglinide 10 mg three times daily over the last 3 years. He initiated vadadustat 300 mg once daily orally on day X owing to renal anemia (hemoglobin A1c: 7.4% and estimated glomerular filtration rate: 28.0 mL/min/1.73 m2). On day 23, he developed hypoglycemia with a blood glucose level of 67 mg/dL. The mean blood glucose level ± standard deviation was lower in the first 24 days of co-administration of vadadustat (before breakfast: 94 ± 14 mg/dL, before lunch: 109 ± 24 mg/dL, and before dinner: 126 ± 39 mg/dL) than in the last 2 weeks (before breakfast: 108 ± 14 mg/dL, before lunch: 122 ± 24 mg/dL, and before dinner: 158 ± 39 mg/dL). Considering the timing of the concomitant administration of vadadustat, hypoglycemia may have been caused by the drug-drug interaction between sitagliptin and vadadustat, and he discontinued treatment with vadadustat. The mean blood glucose levels improved two weeks after the discontinuation of vadadustat (before breakfast: 121 ± 25 mg/dL, before lunch: 147 ± 38 mg/dL, and before dinner: 161 ± 36 mg/dL). The drug interaction probability scale was classified as "Probable" (5 points). CONCLUSIONS: Hypoglycemia was observed when sitagliptin, mitiglinide, and vadadustat were concomitantly administered, which may have resulted in a drug-drug interaction between vadadustat and sitagliptin via OAT3 inhibition in the renal tubules.

Fever as a risk factor causing delayed elimination of methotrexate in pediatric patients receiving high doses of cancer chemotherapy.

PURPOSE: Delayed elimination of methotrexate (MTX) has been reported to be caused by a number of factors. In order to identify these causes, we retrospectively investigated the risk factors for delayed elimination in pediatric patients who received high doses of MTX. SUBJECTS AND METHODS: The study included 69 courses of therapy involving 22 patients who received more than 1000 mg/m(2) of MTX. Plasma MTX concentrations 48 h (C48) and 72 h (C72) after infusion were used as indices of MTX elimination. RESULTS: Neither C48 nor C72 was directly proportional to the dose of MTX infused. Both C48 and C72 were significantly higher in patients who developed fever of above 38 degrees C within a 10-day period (i.e., from 7 days before to 3 days after infusion) than in patients with no fever. Subgroup analysis revealed that C72 was significantly higher in patients who either developed fever and received antipyretics or developed fever but did not receive antipyretics than in patients who did not develop fever and did not receive antipyretics. Changes in the serum creatinine concentrations before and after MTX infusion revealed that renal function was significantly decreased in patients who developed fever compared to patients without fever. CONCLUSIONS: The present results suggest that the development of fever is one of the main risk factors for the delayed elimination of MTX.

Comparative evaluation of digoxin concentrations determined by three assay systems: TDx, IMx and OPUS.

Digoxin concentrations measured by three automated immunoassay systems, i.e. OPUS, TDx and IMx assays, were compared in order to evaluate precision and accuracy performance, and data compatibility. Coefficients of variation for all methods in within-run and between-run precision were less than 10% at weighed-in concentrations of 0.545, 1.090 and 2.180 ng/ml. The accuracy relative to the three weighed-in concentrations ranged from 97% to 123% for all methods. One hundred and three plasma samples from 60 patients receiving digoxin were used to evaluate the data compatibility. Digoxin concentrations measured by the three immunoassay systems correlated well with one another. These results suggest that there are few problems when switching between digoxin assay methods, and that IMx and OPUS are more useful than TDx because they do not require sample pretreatment. The digoxin concentrations of the plasma samples from one patient receiving both digoxin and potassium canrenoate were investigated as a case report. The digoxin concentrations measured by TDx and IMx became higher than those measured by OPUS after starting the combination treatment. In another patient suffering from bilirubinaemia, the digoxin concentrations measured by TDx or IMx were higher than those measured by OPUS. These results suggest that OPUS has a higher specificity for measuring the plasma digoxin concentrations compared with TDx or IMx.