Clinical Pharmacology & Therapeutics最新文献

Disproportionality analyses suggested a cardiovascular risk signal for romosozumab, while statistically significant associations were not found in the real-world database studies. Therefore, a larger comparative study was necessary to examine this signal. This study aimed to compare the cardiovascular risks of romosozumab with those of teriparatide in the overall population and in groups with a history of major adverse cardiovascular events (MACE). A new user cohort study was conducted using Japan's national claims database. Patients aged ≥ 40 years who initiated romosozumab or teriparatide between March 2019 and March 2023 were analyzed. A multivariable Cox proportional hazards model was used to estimate the adjusted hazard ratio (aHR) for MACE. Subgroup analyses were conducted based on MACE history. A total of 251,219 romosozumab and 500,445 teriparatide users were analyzed (most common age group was 80-89 years for both drugs; men: 9.33% for romosozumab and 14.14% for teriparatide). MACE occurred in 1853 romosozumab and 3427 teriparatide users, with incidence rates of 1.09 and 1.22 per 100 person-years, respectively. The aHR (95% confidence interval [CI]) for romosozumab compared with teriparatide was 1.00 (0.94-1.06). In subgroup analyses based on MACE history, the aHRs (95% CI) for no history, for the one-year period leading up to t₀, and for more than 1 year before t₀ were 1.01 (0.95-1.08), 0.93 (0.72-1.21), and 1.00 (0.85-1.18), respectively. In conclusion, no statistically significant difference in MACE risk was observed between romosozumab and teriparatide in Japan's national claims database, regardless of MACE history.

Cheng, S., Al-Kofahi, M., Leeder, J.S. and Brown, J.T. (2024), Population Pharmacokinetic Analysis of Atomoxetine and its Metabolites in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder. Clin Pharmacol Ther, 115: 1033-1043. https://doi.org/10.1002/cpt.3155.

In the article cited above, affiliations for the first two authors were published in the incorrect order. The correct order is shown below; we regret this error.

Shen Cheng^1,5; Mahmoud Al-Kofahi^1,4; J. Steven Leeder²; Jacob T. Brown³

¹Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA

²Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation, Department of Pediatrics, Children’s Mercy Kansas City, and University of Missouri-Kansas City, Kansas City, Missouri, USA

³Department of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota College of Pharmacy, Duluth, Minnesota, USA

⁴Present address: Gilead Sciences, Inc. Forest City, California, USA

⁵Present address: Metrum Research Group, Tariffville, Connecticut, USA

Traditional drug-food interaction studies of oral anticancer agents have a high patient burden. A patient-friendly alternative approach to studying food effects could be the use of stable isotopically labeled microtracers. A prospective, single-center, open-label, crossover, food effect study with the microtracer ²H₆-alectinib was conducted in patients with ALK-positive, non-small cell lung cancer treated with 600 mg alectinib bidaily. On occasion 1 (fed state), patients received 100 μg ²H₆-alectinib in addition to their usual dose of alectinib and a standardized Dutch breakfast (320-392 kcal and 7.5-7.8 g fat). On occasion 2 (fasted state), patients received ²H₆-alectinib and alectinib after overnight fasting. Pharmacokinetic (PK) samples were collected up to 8 hours after intake of ²H₆-alectinib. The effect of food on relative bioavailability (F) and mean transit time of ²H₆-alectinib was assessed by population PK modeling. Differences in area under the plasma concentration-time curve (AUC) and maximum concentration (C_max) between fed and fasted states were estimated by simulations. MTT in the fed state was 3.14 hours (relative standard error (RSE): 16.0%). MTT and F in the fasted state were 28% (RSE: 20.5%) and 35% (RSE: 12.4%) lower, respectively, compared to the fed state. The geometric mean ratio (fed vs. fasted) of AUC and C_max was 1.52 (90% confidence interval (CI): 1.25-1.89) and 1.42 (90% CI: 1.16-1.76), respectively. These results showed that the intake of a Dutch breakfast leads to a higher total exposure of alectinib. More importantly, the feasibility of a microtracer food effect study to reduce patient burden was demonstrated.

Pediatric drug development has achieved remarkable success in the last 20 years with over 1,000 products studied in pediatric patients. This success has been driven in part by an increased understanding of pediatric disease processes. The aspect that has been largely overlooked is the potential adverse effect of new drugs on pediatric developmental processes. The realization of this risk comes with the understanding that we could not predict another thalidomide worldwide tragedy even 70 years later.