This clinical trial was conducted to evaluate the pharmacokinetics and pharmacodynamics of tegoprazan when coadministered with amoxicillin/clarithromycin in healthy subjects. Cohort 1 was an open‐label, randomized multiple‐dose study to evaluate the mutual interaction of tegoprazan and amoxicillin/clarithromycin on the disposition of 3 tested drugs including tegoprazan M1 metabolite and 14‐hydroxyclarithromycin (14‐OH‐clarithromycin). Cohort 2 was an open‐label, randomized, active‐controlled, parallel multiple‐dose study to compare the intragastric pH profile after multiple oral doses of 50 or 100 mg tegoprazan coadministered with amoxicillin/clarithromycin 1000/500 mg for 7 days and pantoprazole‐based triple therapy as the comparator arm. The coadministration of tegoprazan with amoxicillin/clarithromycin increased Css,max (2.2‐fold) and AUCτ (2.7‐fold) of tegoprazan and M1 (2.1‐ and 2.2‐fold for Css,max and AUCτ, respectively) compared with administration of tegoprazan alone. The Css,max and AUCτ of 14‐OH‐clarithromycin increased by 1.7‐ and 1.8‐fold, respectively; the disposition of amoxicillin and clarithromycin were not significantly changed. On days 1 and 7 of treatment, tegoprazan‐based therapies (both 50‐ and 100‐mg therapies) maintained pH above 6 for more than 88% of the 24‐hour period, which was significantly longer compared with pantoprazole‐based therapy. Tegoprazan either alone or in combination with amoxicillin/clarithromycin was well tolerated in healthy subjects. In conclusion, the exposure of tegoprazan was increased after coadministration of amoxicillin/clarithromycin, which led to increase pharmacodynamic response measured by intragastric pH compared with tegoprazan alone. Therefore, tegoprazan‐based triple therapy would be effective therapeutic regimen to manage intragastric pH in terms of gastric or duodenal ulcers healing, treatment of gastroesophageal reflux disease, and Helicobacter pylori eradication.

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The wide variability of isoniazid (INH) pharmacokinetics is mainly attributed to the trimodal N‐acetyltransferase 2 (NAT2) acetylator phenotype, that is, rapid, intermediate, and slow. Consequently, a uniform INH dose in current clinical practice may lead to treatment failure and emergence of drug resistance. There is a lack of studies on specific doses of INH for different NAT2 acetylator phenotypes among tuberculosis (TB) patients. Therefore, we aimed to provide insight into the optimal dosing of INH for each NAT2 acetylator phenotype with respect to the probability of achieving a pharmacokinetic (PK)/pharmacodynamic target. PK, the NAT2 genotype, and clinical data were collected in a multicenter prospective cohort study conducted at 13 clinical centers in Korea. Population PK modeling and simulation were carried out. Data from 454 TB patients were divided into a training data set and a test data set at a ratio of 4 to 1. The PK of the training data were best described by a 2‐compartment model with allometric scaling for body size effect. Importantly, NAT2 acetylator phenotypes significantly affected the apparent clearance. Our model, which provided better predictive performance compared with previously published models, was evaluated by external validation using the test set. The simulation for assessing target efficacy and toxicity indicated that the best INH dosing regimens for Korean tuberculosis patients were once‐daily doses of 400, 300, and 200 mg for rapid, intermediate, and slow acetylators, respectively. In conclusion, our study provides a step forward in precision dosing for antituberculosis management.

Background:The depth of anesthesia is an important factor in surgical prognosis. The neurotoxic effect of chemotherapeutic drugs affects the sensitivity to anesthetics. The purpose of this study is to find out whether the effect-site concentration (Ce) of propofol for loss of consciousness (LOC) differs in patients with preoperative chemotherapy treatment.Methods: 60 patients scheduled for surgery for colorectal cancer under general anesthesia were included in this study. Those who had chemotherapy were the experimental (C) group, and those without prior history of chemotherapy were the control (N) group. Propofol was administered as an effect-site target-controlled infusion and the Modified Observer's Assessment of Alertness/Sedation scale (MOAA/S) was evaluated. When the plasma concentration and the Ce became the same, if the MOAA/S score did not change, the target Ce was increased by 0.2 μg•ml -1 , otherwise Ce was maintained for 2 min and then increased. Results:The values of Ce of propofol for LVC in group C and N were 2.40 ± 0.39 and 2.29 ± 0.39 μg•ml -1 (P = 0.286), and for LOC in group C and N were 2.69 ± 0.43 and 2.50 ± 0.36 μg•ml -1 (P = 0.069), respectively. There was no significant difference in Ce values between the two groups.Conclusions: Chemotherapy did not affect the Ce of propofol for LVC and LOC in colorectal cancer patients.

BackgroundSimultaneous prescription of clopidogrel and low-dose aspirin is recommended for the treatment of acute coronary syndrome because of improvements in efficacy and patient compliance. In this study, the pharmacokinetics of a fixed-dose combination (FDC) of clopidogrel and aspirin was compared with coadministration of individual formulations to clarify the equivalence of the FDC.MethodsThis was a randomized, open-label, two-period, two-treatment, crossover study in healthy Korean men aged 20–55 years. Subjects received two FDC capsules of clopidogrel/aspirin 75/100 mg (test) or two tablets of clopidogrel 75 mg and two capsules of aspirin 100 mg (reference) with a 14-day washout period. Plasma concentrations of clopidogrel, aspirin, and salicylic acid were measured using validated ultraperformance liquid chromatography–tandem mass spectrometry. Bioequivalence was assessed by analysis of variance and calculation of the 90% confidence intervals (CIs) of the ratios of the geometric means (GMRs) for AUClast and Cmax for clopidogrel and aspirin.ResultsSixty healthy subjects were enrolled, and 53 completed the study. Clopidogrel, aspirin, and salicylic acid showed similar absorption profiles and no significant differences in Cmax, AUClast, and Tmax between FDC administration and coadministration of individual formulations. The GMRs (90% CI) for the Cmax and AUClast of clopidogrel were 1.08 (0.95, 1.23) and 0.93 (0.84, 1.03), respectively. The GMRs (90% CI) for the Cmax and AUClast of aspirin were 0.98 (0.84, 1.13) and 0.98 (0.93, 1.04), respectively. Both treatments were well tolerated in the study subjects.ConclusionThe FDC of clopidogrel and aspirin was bioequivalent to coadministration of each individual formulation. The FDC capsule exhibited similar safety and tolerability profiles to the individual formulations. Therefore, clopidogrel/aspirin 75 mg/100 mg FDC capsules can be prescribed to improve patient compliance.