Assessing the applicability and appropriateness of ChatGPT in answering clinical pharmacy questions.

OBJECTIVES: Clinical pharmacists rely on different scientific references to ensure appropriate, safe, and cost-effective drug use. Tools based on artificial intelligence (AI) such as ChatGPT (Generative Pre-trained Transformer) could offer valuable support. The objective of this study was to assess ChatGPT's capacity to correctly respond to clinical pharmacy questions asked by healthcare professionals in our university hospital. MATERIAL AND METHODS: ChatGPT's capacity to respond correctly to the last 100 consecutive questions recorded in our clinical pharmacy database was assessed. Questions were copied from our FileMaker Pro database and pasted into ChatGPT March 14 version online platform. The generated answers were then copied verbatim into an Excel file. Two blinded clinical pharmacists reviewed all the questions and the answers given by the software. In case of disagreements, a third blinded pharmacist intervened to decide. RESULTS: Documentation-related issues (n=36) and drug administration mode (n=30) were preponderantly recorded. Among 69 applicable questions, the rate of correct answers varied from 30 to 57.1% depending on questions type with a global rate of 44.9%. Regarding inappropriate answers (n=38), 20 were incorrect, 18 gave no answers and 8 were incomplete with 8 answers belonging to 2 different categories. No better answers than the pharmacists were observed. CONCLUSIONS: ChatGPT demonstrated a mitigated performance in answering clinical pharmacy questions. It should not replace human expertise as a high rate of inappropriate answers was highlighted. Future studies should focus on the optimization of ChatGPT for specific clinical pharmacy questions and explore the potential benefits and limitations of integrating this technology into clinical practice.

[Clinical pharmacy in four French-speaking university hospitals, integration and supervision of clinical pharmacists: An exploratory study]. / Pharmacie clinique au sein de quatre CHU de la francophonie, intégration et encadrement des pharmaciens cliniciens : une étude exploratoire.

BACKGROUND: Pharmacy practice continues to evolve worldwide. The clinical role of the pharmacists is increasingly recognized and their integration into the health care team is irreversible. Despite this progress, there are still a wide disparity in the scope of practice provided by hospital pharmacists around the world. This disparity can be attributed to a variety of factors. OBJECTIVES: The primary objective is to describe the organization of clinical pharmacy in four university hospitals in four French-speaking countries. The secondary objective is to identify similarities and differences and to identify perspectives for the future. METHODS: This is an exploratory cross-sectional descriptive study. The study targeted a university hospital (CHU) in France, Belgium, Switzerland and Canada (Quebec). A volunteer expert pharmacist involved in the management of clinical pharmacy at each hospital was approached at the initiative of a team member. A working group of five pharmacists was set up. RESULTS: During the year 2021, the group met virtually on ten occasions. Although all institutions have an academic mission, they have very different numbers of beds and volumes of activity. The number of pharmacists is also very different (0.83 FTE pharmacist/1000 admissions in Belgium, 0.22 in France, 0.59 in Switzerland and 2.39 in Quebec). In all countries, pharmacists provide clinical pharmacy services to patients in a centralised or decentralised manner, including, to various extent, prescription analysis, medication reconciliation, pharmaceutical interviews and discharge plans. CONCLUSIONS: Clinical pharmacy practice is very heterogeneous in a selection of four French-speaking teaching hospitals. Identification of similarities and differences may inspire improvements in the organization of clinical pharmacy activity. This work has contributed to the establishment of a community of practice on clinical pharmacy in the French-speaking world.

Population pharmacokinetics of ganciclovir in solid-organ transplant recipients receiving oral valganciclovir.

Valganciclovir (VGC) is an oral prodrug of ganciclovir (GCV) recently introduced for prophylaxis and treatment of cytomegalovirus infection. Optimal concentration exposure for effective and safe VGC therapy would require either reproducible VGC absorption and GCV disposition or dosage adjustment based on therapeutic drug monitoring (TDM). We examined GCV population pharmacokinetics in solid organ transplant recipients receiving oral VGC, including the influence of clinical factors, the magnitude of variability, and its impact on efficacy and tolerability. Nonlinear mixed effect model (NONMEM) analysis was performed on plasma samples from 65 transplant recipients under VGC prophylaxis or treatment. A two-compartment model with first-order absorption appropriately described the data. Systemic clearance was markedly influenced by the glomerular filtration rate (GFR), patient gender, and graft type (clearance/GFR = 1.7 in kidney, 0.9 in heart, and 1.2 in lung and liver recipients) with interpatient and interoccasion variabilities of 26 and 12%, respectively. Body weight and sex influenced central volume of distribution (V(1) = 0.34 liter/kg in males and 0.27 liter/kg in females [20% interpatient variability]). No significant drug interaction was detected. The good prophylactic efficacy and tolerability of VGC precluded the demonstration of any relationship with GCV concentrations. In conclusion, this analysis highlights the importance of thorough adjustment of VGC dosage to renal function and body weight. Considering the good predictability and reproducibility of the GCV profile after treatment with oral VGC, routine TDM does not appear to be clinically indicated in solid-organ transplant recipients. However, GCV plasma measurement may still be helpful in specific clinical situations.

Disposition of valganciclovir during continuous renal replacement therapy in two lung transplant recipients.

OBJECTIVES: To determine whether valganciclovir 450 mg every 48 h for cytomegalovirus (CMV) prophylaxis provides appropriate ganciclovir exposure in solid organ transplant recipients during continuous renal replacement therapy (CRRT). PATIENTS AND METHODS: Ganciclovir pharmacokinetics was intensively studied in two lung transplant recipients under valganciclovir 450 mg every 48 h over one dosing interval. In vitro experiments using blank whole blood spiked with ganciclovir further investigated exchanges between plasma and erythrocytes. RESULTS: Ganciclovir disposition was characterized by apparent total body clearance of 3.3 and 5.8 L/h, terminal half-life of 16.9 and 14.1 h, and apparent volume of distribution of 60.3 and 104.9 L in Patients 1 and 2, respectively. The observed sieving coefficient was 1.05 and 0.96, and the haemofiltration clearance was 3.3 and 3.1 L/h. In vitro experiments confirmed rapid efflux of ganciclovir from red blood cells into plasma, increasing the apparent efficacy of haemofiltration. CONCLUSIONS: A valganciclovir dosage of 450 mg every 48 h appears adequate for patients under CRRT requiring prophylaxis for CMV infection, providing concentration levels in the range reported for 900 mg once daily dosing outside renal failure.

Determination of aciclovir and ganciclovir in human plasma by liquid chromatography-spectrofluorimetric detection and stability studies in blood samples.

A sensitive HPLC method has been developed for the assay of aciclovir and ganciclovir in human plasma, by HPLC coupled with spectrofluorimetric detection. Plasma (1000 microl), with 9-ethyl-guanine added as internal standard, is submitted to protein precipitation with trichloroacetic acid solution 20%. The supernatant, evaporated to dryness at 37 degrees C, is reconstituted in 100 microl of a solution of sodium heptanosulfonate 0.4% adjusted with acetic acid to pH 2.60 and a 30 microl volume is then injected onto a Nucleosil 100-5 microm C18 column. Aciclovir and ganciclovir are analysed by spectrofluorimetric detection set at 260 nm (excitation) and 380 nm (emission) using a gradient elution program with solvents constituted of acetonitrile and a solution of sodium heptanosulfonate 0.4% adjusted to pH 2.60. The calibration curves are linear between 0.1 and 10 microg/ml. The mean absolute recovery of aciclovir and ganciclovir are 99.2+/-2.5 and 100.3+/-2.5%, respectively. The method is precise (with mean inter-day C.V.s within 1.0-1.6% for aciclovir and 1.2-3.5% for ganciclovir), and accurate (range of inter-day deviations -1.6 to +1.6% for aciclovir and -0.4 to -1.4% for ganciclovir). The method has been applied in stability studies of ganciclovir in patients' blood samples, demonstrating its good stability in plasma at -20 degrees C and at room temperature. The distribution of ganciclovir and aciclovir in plasma and red blood cells was also investigated in vitro in spiking experiments with whole blood, which showed an initial drop of ganciclovir and aciclovir levels in plasma (about -25%) due to the cellular uptake of aciclovir and ganciclovir by red blood cells. The method has been validated and is currently applied in a clinical study assessing the ganciclovir plasma concentration variability after administration of valganciclovir in a population of solid organ transplant patients.