Population Pharmacokinetics and Pharmacodynamics of the Therapeutic and Adverse Effects of Ketamine in Patients With Treatment-Refractory Depression

We aimed to develop population pharmacokinetic/pharmacodynamic (PK/PD) models that can effectively describe ketamine and norketamine PK/PD relationships for Montgomery–Åsberg Depression Rating Scale (MADRS) scores, blood pressure (BP), and heart rate (HR) following i.v., s.c., and i.m. ketamine administration in patients with treatment-refractory depression. Ketamine PK/PD data were collected from 21 treatment-refractory depressed participants who received ketamine (dose titration 0.1–0.5 mg/kg as single doses) by i.v., s.c., or i.m. administration. Model development used nonlinear mixed effect modeling. Ketamine and norketamine PK were best described using two-compartment models with first-order absorption after s.c. and i.m. administration. Estimated ketamine bioavailability after i.m. and s.c. was ~ 64% with indistinguishable first-order absorption rate constants. Allometric scaling of body weight on all clearance and volumes of distribution improved the model fit. The delay in the concentration-response relationship for MADRS scores was best described using a turnover model (turnover time ~ 42 hours), whereas for the BP and HR rates this was an immediate effect model. For all PD effects, ketamine alone was superior to models with norketamine concentration linked to an effect. No covariates were identified for PD effects. The estimated half-maximal effective concentration from the MADRS score, BP, and HR were 0.44, 468, and 7,580 ng/mL, respectively. The integrated population models were able to effectively describe the PK/PD relationships for MADRS scores, BP, and HR after i.v., s.c., and i.m. ketamine administration. These findings allow for a deeper understanding of the complex relationships between route of ketamine administration and clinical response and safety

Role of pharmacists in the care of adult asthma patients: A scoping review

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record Background: Asthma is a common long-term condition that affects people of all ages. Evidence suggests that a significant proportion of asthma patients in the Gulf Cooperation Council (GCC) do not receive appropriate diagnosis, monitoring and/or treatment. When inadequately treated, asthma can negatively affect quality of life and may lead to hospitalisation and death. Although pharmacists play a role in asthma care globally, there appears to be no defined role for pharmacists in providing care to patients with asthma in the GCC countries. Aim: This scoping review aims to review and summarise studies conducted in the GCC countries involving pharmacists in the management of adults with asthma or evaluating pharmacists' asthma care knowledge and/or skills. Method: A systematic scoping review was undertaken. Seven databases were searched using relevant search terms for articles published up to May 2023. Studies that evaluated pharmacists’ roles, knowledge and skills in providing asthma care to adults in the United Arab Emirates (UAE), Qatar, Kuwait, Oman, Saudi Arabia, and Bahrain were considered eligible for inclusion. Extracted data were collated using tables and used to produce narrative descriptive summaries. Results: Out of the 1588 search results, only seven studies met the inclusion criteria. Of those, only one developed and tested a pharmacist-led inhaler technique educational intervention in the UAE within community pharmacy setting for asthma patients. The remaining six studies assessed community pharmacists’ knowledge in providing asthma management and patient education in UAE, Saudi Arabia and Qatar. The quality of the included studies varied with four relying on simulated patients to assess pharmacists’ knowledge. The study that tested the intervention suggested improvement in inhaler technique and asthma symptoms control after receiving the intervention. The findings suggest a need to improve pharmacists’ knowledge of inhaler technique demonstration (mainly Metered Dose Inhalers), asthma management advice and assessment of asthma control and medication use. Conclusion: This review highlights a lack of research on pharmacist-led asthma interventions and identifies training needs to enable pharmacists to be involved in asthma care in the GCC countries. Future research could develop approaches involving pharmacists to improve asthma care and outcomes in the region.University of Exeter Global MENA Development fundUniversity of Sharja