Background and Objectives Tramadol is commonly prescribed to manage chronic pain in older patients. However, there is a gap in the literature describing the pharmacokinetic parameters for tramadol and its active metabolite (O-desmethyltramadol [ODT]) in this population. The objective of this study was to develop and evaluate a population pharmacokinetic model for tramadol and ODT in older patients. Methods Twenty-one patients who received an extended-release oral tramadol dose (25–100 mg) were recruited. Tramadol and ODT concentrations were determined using a validated liquid chromatography/tandem mass spectrometry method. A population pharmacokinetic model was developed using non-linear mixed-effects modelling. The performance of the model was assessed by visual predictive check. Results A two-compartment, first-order absorption model with linear elimination best described the tramadol concentration data. The absorption rate constant was 2.96/h (between-subject variability [BSV] 37.8%), apparent volume of distribution for the central compartment (V₁/F) was 0.373 l (73.8%), apparent volume of distribution for the peripheral compartment (V₂/F) was 0.379 l (97.4%), inter-compartmental clearance (Q) was 0.0426 l/h (2.19%) and apparent clearance (CL/F) was 0.00604 l/h (6.61%). The apparent rate of metabolism of tramadol to ODT (k_t) was 0.0492 l/h (78.5%) and apparent clearance for ODT (CL_m) was 0.143 l/h (21.6%). Identification of Seniors at Risk score (ISAR) and creatinine clearance (CrCL) were the only covariates included in the final model, where a higher value for the ISAR increased the maximum concentration (C_max) of tramadol and reduced the BSV in Q from 4.71 to 2.19%. A higher value of CrCL reduced tramadol C_max and half-life (T_1/2) and reduced the BSV in V₂/F (from 148 to 97.4%) and in CL/F (from 78.9 to 6.61%). Conclusion Exposure to tramadol increased with increased frailty and reduced CrCL. Prescribers should consider patients frailty status and CrCL to minimise the risk of tramadol toxicity in such cohort of patients.

Background/Objectives: Proton pump inhibitors (PPIs) are amongst the most commonly prescribed classes of medication. However, inappropriate PPI use can lead to several adverse drug reactions (ADRs). Limited data exist on factors contributing to the risk of ADRs associated with PPI prescribing patterns in the Eastern Region of Saudi Arabia. This retrospective, cross-sectional study aimed to assess the prevalence and the pattern of PPI use and to identify factors contributing to the risk of ADRs. Methods: Data were collected from electronic medical records of patients at Al-Qateef Central Hospital from January 2020 to December 2021. The inclusion criteria included patients aged ≥40 years attending an outpatient medical care clinic. PPI prescribing patterns were categorized based on their dosage intensity into low-dose, medium-dose (MD), and high-dose (HD) categories. Binary and multinominal logistic regression models were used to determine the relationship between PPI prescribing patterns and use, categorized by MD or HD, and patient characteristics, adjusted for significant covariates. Results are presented as adjusted odds ratio (OR) with corresponding 95% confidence intervals (95% CI). Results: The study included 41,084 patients. The prevalence of PPI prescribing was 31%. PPI users were more frequently found to be females than males (52% vs. 50%, p = 0.013); they were also likely to be prescribed more medications (7 vs. 6, p < 0.001), but less likely to have gastritis-related diseases (34% vs. 32%, p < 0.001) compared to non-users. PPI HD users were more likely male (56% vs. 43%, p < 0.001), older (53 vs. 52 years, p < 0.001), and prescribed more medications (11.8 vs. 2.8, p < 0.001) compared to MD users. PPI usage was associated with concurrent use of antiplatelet drugs (OR = 1.08, 95% CI 1.01–1.15). An increasing number of prescribed medications was associated with HD usage (OR = 1.13, 95% CI 1.12–1.14), but negatively associated with MD usage (OR = 0.7 95% CI 0.69–0.71). Female gender was negatively associated with HD usage (OR = 0.85, 95% CI 0.79–0.91). Conclusions: Our findings indicate that 31% of the included cohort were prescribed PPI. Inappropriate PPI prescribing related to the drug’s omission is a concern as PPI non-users presented with valid indications such as gastritis. Male gender and increasing NPM were the common factors contributing to increased risk of PPI ADR. This study points to the importance of re-evaluating PPI use to ensure effective therapy with minimum risks of ADR.