Population pharmacokinetic models of tacrolimus in paediatric solid organ transplant recipients: A systematic review.

AIMS: This study aimed to provide up-to-date information on paediatric population pharmacokinetic models of tacrolimus and to identify factors influencing tacrolimus pharmacokinetic variability. METHODS: Systematic searches in the Web of Science, PubMed, Scopus, Science Direct, Cochrane, EMBASE databases and reference lists of articles were conducted from inception to March 2023. All population pharmacokinetic studies of tacrolimus using nonlinear mixed-effect modelling in paediatric solid organ transplant patients were included. RESULTS: Of the 21 studies reviewed, 62% developed from liver transplant recipients and 33% from kidney transplant recipients. Most studies used a 1-compartment model to describe tacrolimus pharmacokinetics. Body weight was a significant predictor for tacrolimus volume of distribution (Vd/F). The estimated Vd/F for 1-compartment models ranged from 20 to 1890 L, whereas the peripheral volume of distribution (Vp/F) for 2-compartment models was between 290 and 1520 L. Body weight, days post-transplant, CYP3A5 genotype or haematocrit were frequently reported as significant predictors of tacrolimus clearance. The estimated apparent clearance values range between 0.12 and 2.18 L/h/kg, with inter-individual variability from 13.5 to 110.0%. Only 29% of the studies assessed the generalizability of the models with external validation. CONCLUSION: This review highlights the potential factors, modelling approaches and validation methods that impact tacrolimus pharmacokinetics in a paediatric population. The clinician could predict tacrolimus clearance based on body weight, CYP3A5 genotype, days post-transplant or haematocrit. Further research is required to determine the relationship between pharmacogenetics and tacrolimus pharmacodynamics in paediatric patients and confirm the applicability of nonlinear kinetics in this population.

Prevalence and determinants of potentially inappropriate medications in elderly inpatients in Thailand: a retrospective observational study based on the 2019 Beers criteria.

Background: The prevalence of potentially inappropriate medications (PIMs), including NSAIDs, first-generation antihistamines, tricyclic antidepressants (TCAs), and benzodiazepines among elderly inpatients in Thailand, based on the 2019 Beers criteria, is insufficiently investigated. Methods: This study retrospectively examined 300 elderly patients in a Thai tertiary hospital, assessing four PIM classes based on the 2019 Beers criteria and exploring factors and variations in PIM prescription patterns across different phases of hospitalisation. Results: The study found an overall PIM prescription rate of 28%, consisting of: benzodiazepines (14%), first-generation antihistamines (9%), NSAIDs (3%), and TCAs (2%). Patients taking at least 5 medications prior to admission were more likely to receive PIMs (OR 3.77, 95% CI 1.15-12.35). Furthermore, PIM prescription was significantly associated with age, showing a 4.8% yearly increase (p = 0.01), and the number of comorbidities increased by 16.2% per unit (p = 0.021). Additionally, PIM use during admission was significantly linked to a longer hospital stay (OR 3.32, 95% CI 1.50-7.33). Conclusions: These findings emphasise the need for continued monitoring and optimisation of medication management, and collaboration between pharmacists and physicians to review and adjust prescriptions, especially in elderly inpatients experiencing polypharmacy and multiple comorbidities.

Community Pharmacists' Experiences and Attitudes towards the Provision of Sexual and Reproductive Health Services: An International Survey.

Access to comprehensive sexual and reproductive health (SRH) services remains a challenge worldwide. Describing community pharmacists' SRH services in countries with different scopes of practice will aid in understanding how pharmacists view their roles and how to support them in providing needed services. A cross-sectional web-based survey was administered to pharmacists working in community pharmacies in Japan, Thailand, and Canada. The survey covered 7 SRH categories: pregnancy tests, ovulation tests, contraception, emergency contraception, sexually transmitted and blood-borne infections, maternal and perinatal health, and general sexual health. Descriptive statistics were used to analyze the data. A total of 922 eligible responses were included in the analysis (Japan = 534, Thailand = 85, and Canada = 303). Most Thai and Canadian participants reported dispensing hormonal contraceptives (Thailand = 99%, Canada = 98%) and emergency contraceptive pills (Thailand = 98%, Canada = 97%). Most Japanese participants provided patient education on barrier contraceptives for men (56%) and information on the safety of medications in pregnancy (74%) and breastfeeding (76%). The majority of participants expressed interest in additional training and expanding their roles in SRH. Sharing international experiences can guide challenges faced by the evolution of pharmacists' practice in SRH. Providing pharmacists support could help their readiness for this role.

Defining and supporting a professional role for pharmacists associated with traditional and complementary medicines: a cross-country survey of pharmacists.

Introduction: An estimated 80% of the world's population use traditional and complementary medicine (T&CM) products as part of their healthcare, with many accessed through pharmacy. This cross-cultural study posed a set of professional practice responsibilities and actions to pharmacists related to T&CM products, with a view toward developing consensus, safeguarding, and promoting the health of the public. Methods: Data were collected from 2,810 pharmacists across nine countries during 2022 via a cross-sectional online survey reported in accordance with the guidelines of STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) and the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). Results: Of the 2,810 participants from nine countries, 2,341 completed all sections of the survey. Of these, most agreed (69%) that T&CM product use was common in the community they served, but most did not have adequate training to support consumer needs. Over 75% acknowledged that there were known and unknown safety risks associated with T&CM use. Of 18 professional responsibilities posed, 92% agreed that pharmacists should be able to inform consumers about potential risks, including T&CM side effects and drug-herb interactions. The provision of accurate scientific information on the effectiveness of T&CM products, skills to guide consumers in making informed decisions, and communication with other healthcare professionals to support appropriate and safe T&CM product use were all ranked with high levels of agreement. In order to effectively fulfill these responsibilities, pharmacists agreed that regulatory reforms, development of T&CM education and training, and access to quality products supported by high-quality evidence were needed. Conclusion: General agreement from across nine countries on eighteen professional responsibilities and several stakeholder actions serve as a foundation for the discussion and development of international T&CM guidelines for pharmacists.

Comparison of area under the curve for vancomycin from one- and two-compartment models using sparse data.

BACKGROUND AND OBJECTIVE: Vancomycin pharmacokinetics have been described by both one- and two-compartment models. One-compartment models are widely used to predict the area under the curve (AUC), a useful parameter for determining the efficacy and safety of vancomycin, based on sparse data collected during therapeutic drug monitoring. It is uncertain whether AUCs from one-compartment models with sparsely sampled data can sufficiently represent the true AUC. This study aimed to compare AUC estimates from one- and two-compartment models using sparse data. The reliability of AUCs from models constructed with trough-only data was also assessed. METHODS: A previously published robust model was used to simulate vancomycin concentration points at 15 min intervals in 100 patients. From these simulated data, the reference AUC (AUCref) was calculated and two depleted dataset versions (trough-only and peak-trough datasets) were also created. One- and two-compartment models were built from the depleted datasets with the use of NONMEM. Vancomycin 24-hour AUC was calculated from concentration-time profiles of each model by a linear trapezoidal formula at three different time periods: 0-24 hours (AUC0-24), 24-48 hours (AUC24-48) and 0-48 hours (AUCavg). The deviation of each of the AUCs from the AUCref was examined to assess the AUC predictability of models from sparse data. The difference in AUCs between one- and two-compartment models was analysed from statistical and clinical perspectives. RESULTS: When assessing the deviation of each AUC from the AUCref, the one-compartment model from both peak-trough and trough-only data could adequately represent the true AUC with no statistically significant differences. Two-compartment model from peak-trough data also provided similar AUC estimates with the AUCref. However, AUCs from the two-compartment model with trough-only data did not adequately represent the true AUC, with significant differences of 25.16% for AUC0-24, 15.92% for AUC24-48 and 19.45% for AUCavg. CONCLUSION: Regardless of statistically significant differences between AUCs from one- and two-compartment models, the level of difference was acceptable from the clinical perspective, being <17% in models from peak-trough data. Therefore, both one- and two-compartment models with sparse data having at least a pair of peak-trough data per patient could be reliable for predicting AUC. Furthermore, AUCs of the one-compartment model from trough-only data did not show a significant difference from the AUCref. Hence, one-compartment models developed from trough-only data could be useful for predicting AUC when models with rich data are not available for the intended population. However, it is suggested that the use of the two-compartment model built from trough-only data should be avoided.

The impact of dosage of sustained-release formulation on valproate clearance and plasma concentration in psychiatric patients: analysis based on routine therapeutic drug monitoring data.

Pharmacokinetic parameters were compared between 2 dosages of valproic acid (VPA) sustained-release (SR) formulation in psychiatric patients. A total of 66 psychiatric patients (21 women and 45 men; age range, 18-60 years) receiving 500 mg/d (n = 28) or 1000 mg/d (n = 38) of VPA SR for at least 4 weeks were recruited into the study. A 5-mL blood sample was collected into a plain tube and immediately centrifuged for plasma. Separation of free VPA was further done using Centrifree micropartition devices. Both total and free VPA concentrations (C(total) and C(free)) were analyzed by TDx analyzer with fluorescence polarization immunoassay technique. The patients' characteristics and pharmacokinetic parameters were compared between the 2 dosage groups using independent t test or χ² test where appropriate. The results show that the increment in C(total) (mg/mL) for every milligram-per-kilogram increment in dosage was decreased from 7 ± 3 to 4 ± 1 (mg/L) / (mg/kg) when the total VPA clearance (CL(total)) increased from 6.1 ± 2.6 to 9.0 ± 3.1 mL/kg per hour with the increasing dose in the 500 mg/d and 1000 mg/d groups, respectively (P < 0.05). The increment in C(free) [0.6 ± 0.3 vs 0.5 ± 0.2 (mg/L) / (mg/kg)] and CL(free) (80.4 ± 41.5 vs 92.2 ± 47.6 ml/kg per hour) were not significantly different. Owing to the saturation of protein binding, percent free VPA was significantly increased from 8 ± 3 to 11 ± 3 when the dose was increased from 500 to 1000 mg/d (P < 0.05). In conclusion, an increase in the VPA dose resulted in a disproportional increase between dosage and C(total), whereas a proportional increase between dosage and C(free) still existed. Therefore, our study suggests that the therapeutic range of C(free) is 4 to 12 mg/L based on the therapeutic range of C(total) (45-100 mg/L) for general psychiatric conditions.

Reproductive Health Services: Attitudes and Practice of Japanese Community Pharmacists.

The provision of sexual and reproductive health (SRH) services is an important part of a community pharmacist's role in many countries. However, such services are not traditionally provided by pharmacists in Japan. We surveyed the practice and attitudes regarding the provision of SRH services among Japanese community pharmacists with a focus on reproductive health (RH) topics. The participants were asked about the provision of RH services, attitudes toward their role as SRH providers, and self-reported confidence in providing education to patients on RH topics. We obtained 534 effective responses. About half of the participants reported providing RH services, and only 21% were involved in dispensing emergency contraception pills. Although the proportion of pharmacists providing education on these topics was considerably lower, about 80% recognized the importance of their role as SRH advisors. Confidence in providing patient education about RH topics depended on their experience in providing such services. Most participants were interested in additional SRH training (80%). Our results suggest that training programs could help to expand Japanese community pharmacists' roles as SRH providers and increase their confidence in the education of patients. This study provides useful insights to expand pharmacists' roles in Japan as providers of comprehensive SRH services.