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Aims: The objectives were to investigate the pharmacokinetics, pharmacodynamics and safety of ilaprazole infusion in healthy subjects and patients with esomeprazole as positive control, and then recommend the dosage regimen for Phase 2b/3 studies. Methods: Three clinical studies were performed. First, 16 healthy subjects received infusion of ilaprazole 30 mg or esomeprazole 80 mg. Second, 12 healthy subjects received ilaprazole 20 mg followed by 10 mg once daily for 2 days. Finally, 20 patients with duodenal ulcers received ilaprazole 20 mg followed by 10 mg for 2 days or esomeprazole 40 mg twice daily for 3 days. Serial blood samples were collected and intragastric pH was recorded. Results: The mean percentages time of intragastric pH >6 was 63.6 and 51.7% for healthy subjects after receiving ilaprazole 30 mg and esomeprazole 80 mg. Linear pharmacokinetics was observed when the dose was increased to 30 mg but the effect was saturated. Ilaprazole 20 mg followed by 10 mg for 2 days provided higher plasma exposure in healthy subjects than patients, but the effect was comparable. After multiple administrations, ilaprazole provided similar effect to esomeprazole. Ilaprazole infusion was safe and well tolerated without serious adverse events. Conclusions: Ilaprazole provided comparable effect of pH control to esomeprazole, with lower dose and fewer times of administration. There was no significant difference of ilaprazole between healthy subjects and patients regarding intragastric acid inhibition. A loading dose of ilaprazole 20 mg followed by 10 mg once daily for 2 days was recommended for Phase 2b/3 studies. [ABSTRACT FROM AUTHOR]

Tylerdipine hydrochloride is a novel L‐type and T‐type dual calcium channel antagonist that has the potential effects of expanding blood vessels and lowering blood pressure. It is expected to reduce the side effect of ankle edema observed with other drugs in the same class. A randomized, open‐label, crossover phase 1 study was performed to evaluate the effect of food on the bioavailability of tylerdipine. Fourteen healthy male volunteers were enrolled. The administration of tylerdipine after a high‐fat meal increased the bioavailability of tylerdipine. In the fed state there was a 130% increase in the mean total systemic exposure (AUCinf) and a 73% increase in the mean peak plasma concentration (Cmax) compared with that in the fasting state. The geometric mean ratios (90% confidence interval) of Cmax and AUCinf were 2.54 (1.94, 3.33) and 1.75 (1.50, 2.04) for tylerdipine. The exposures of the 2 main metabolites M2 and M4 were increased by approximately 10% after a high‐fat meal. The median time to peak plasma concentration of tylerdipine showed no difference between fasting and fed states. [ABSTRACT FROM AUTHOR]

l-Valine, l-leucine, l-isoleucine, l-phenylalanine, and l-tyrosine are important proposed biomarkers for the early detection and diagnosis of type 2 diabetes. A simple and selective hydrophilic interaction chromatography with tandem mass spectrometry method was developed for the simultaneous determination of these amino acids in human serum, using stable isotope-labeled amino acids as internal standards. Chromatographic separation was carried out on a Syncronis HILIC column (150 mm × 2.1 mm, 5 μm) with the column temperature of 35°C and a mobile phase consisted of acetonitrile/120 mM ammonium acetate (89:11, v/v), and the run time was 11.0 min. The mass spectrometric analysis was performed using a QTRAP 5500 mass spectrometer coupled with an electrospray ionization source in positive ion mode. As these five amino acids are endogenous compounds in serum, we used the corresponding stable isotope-labeled amino acids to evaluate the matrix effect and recovery in serum. The matrix effect was 98.7-107.3%, and the recovery was 92.7-102.3%. Calibration curves spiked unlabeled amino acids in water were linear over the range of 0.200-100 μg/mL. The accuracy, inter-, and intraday precision were below 10.2%. Analytes were stable during the study. This assay method has been validated and applied to the early diagnosis research of type 2 diabetes. [ABSTRACT FROM AUTHOR]