One of the major concerns for all in vivo experiments is intra- and inter-subject variability, which can be a great source of inaccuracy. The aim of this study is, therefore, to estimate the ability of parallel vs. cross-over design studies in order to describe the relative pharmacokinetic performance of the studied drug formulations. We analyzed the data from a drug development program that examined the performance of innovative abiraterone acetate formulations against the identical reference product in three stages. In stages 1–3, groups A–F were dosed with the reference product once in a parallel manner. Stage 4 was performed to evaluate the intra-individual variability (IIV) by repeated administration of the reference product to the same animals. Although the geometric mean (90% CI) values of abiraterone AUC_last in groups A–F were similar to the IIV group (24.36 (23.79–41.00) vs. 26.29 (20.56–47.00) mg/mL·min·g), the results generated in the isolated parallel groups provided imprecise estimates of the true AUC_last values ranging from 9.62 to 44.62 mg/mL·min·g due to chance. Notably, in 4 out of 15 possible pair comparisons between the parallel groups, the confidence intervals did not include 100%, which is the true ratio for all comparisons tested after identical formulation administration to all groups. A cross-over design can significantly improve the methodology in short-term comparative pre-clinical pharmacokinetic studies, and can provide more precise and accurate results in comparison to more traditional pre-clinical study designs.

Background/Objectives: Omeprazole undergoes degradation in acidic conditions, which makes it unstable in low pHs found in the gastric environment. The vast majority of already marketed omeprazole formulations use enteric polymer coatings to protect the drug from exposure to acidic pH in the stomach, allowing for drug release in the small intestine where the pH is higher. This study aimed to explore the technical aspects of using stomach acid neutralizers as an alternative to polymeric coatings for omeprazole. Methods: After evaluating various neutralizers, magnesium oxide and sodium bicarbonate were chosen to be incorporated into capsules containing omeprazole, which then underwent in vitro dissolution testing to assess their ability to maintain optimal pH levels and ensure appropriate dissolution kinetics. Hygroscopicity and chemical stability of the selected formulation were tested to prove pharmaceutical quality of the product. An in vivo pharmacokinetic study was conducted to demonstrate the efficacy of the omeprazole–sodium bicarbonate formulation in providing faster absorption in humans. Results: Sodium bicarbonate was selected as the most suitable antacid for ensuring omeprazole stabilization. Its quantity was optimized to effectively neutralize stomach acid, facilitating the rapid release and absorption of omeprazole. In vitro studies demonstrated the ability of the formulation to neutralize gastric acid within five minutes. In vivo studies indicated that maximum concentrations of omeprazole were achieved within half an hour. The product met the requirements of pharmaceutical quality. Conclusions: An easily manufacturable, fast-absorbing oral formulation was developed as an alternative to enteric-coated omeprazole.

Dasatinib absorption is pH-dependent, and concomitant use of Proton Pump Inhibitors (PPIs) can substantially reduce dasatinib exposure. Whether this interaction has clinical relevance and affects treatment outcomes in patients with chronic myeloid leukemia (CML) remains unclear. This retrospective cohort study used German statutory health insurance claims data (2010 − 2024). Adults with CML who initiated dasatinib treatment were selected. Patients were classified according to concomitant PPI use around dasatinib initiation. The primary endpoint was time to switch to another systemic CML therapy. Two analytical cohorts were evaluated (incident and prevalent cohorts). Propensity score matching and Cox proportional hazards models were used to compare patients with and without PPI co-medication. Sensitivity analyses censored follow-up at severe adverse events and restricted the population to users of the originator dasatinib formulation. Among 297 dasatinib patients in the incident and 372 in the prevalent cohort, PPI co-medication was observed in approximately 19–21% of patients. After matching, concomitant PPI use was consistently associated with earlier treatment switching. This association reached statistical significance in the prevalent cohort (hazard ratio: 1.87, 95% CI 1.18–2.95; p = .008) and was directionally consistent in the incident cohort. Sensitivity analyses yielded directionally consistent findings. In this large real-world analysis, concomitant PPI use was associated with earlier treatment switching in dasatinib-treated patients with CML. While causality cannot be established, these findings are consistent with the known pH-dependent interaction and reinforce existing recommendations to avoid PPI co-medication during dasatinib therapy whenever feasible.