Aims: Imatinib is considered the standard first‐line treatment in newly diagnosed patients with chronic‐phase myeloid leukaemia (CML). Several imatinib population pharmacokinetic (popPK) models have been developed. However, their predictive performance has not been well established when extrapolated to different populations. Therefore, this study aimed to perform an external evaluation of available imatinib popPK models developed mainly in adult patients, and to evaluate the improvement in individual model‐based predictions through Bayesian forecasting computed by each model at different treatment occasions.Methods: A literature review was conducted through PubMed and Scopus to identify popPK models. Therapeutic drug monitoring data collected in adult CML patients treated with imatinib was used for external evaluation, including prediction‐ and simulated‐based diagnostics together with Bayesian forecasting analysis.Results: Fourteen imatinib popPK studies were included for model‐performance evaluation. A total of 99 imatinib samples were collected from 48 adult CML patients undergoing imatinib treatment with a minimum of one plasma concentration measured at steady‐state between January 2016 and December 2020. The model proposed by Petain et al showed the best performance concerning prediction‐based diagnostics in the studied population. Bayesian forecasting demonstrated a significant improvement in predictive performance at the second visit. Inter‐occasion variability contributed to reducing bias and improving individual model‐based predictions.Conclusions: Imatinib popPK studies developed in Caucasian subjects including α1‐acid glycoprotein showed the best model performance in terms of overall bias and precision. Moreover, two imatinib samples from different visits appear sufficient to reach an adequate model‐based individual prediction performance trough Bayesian forecasting.
The pathologies produced by fungi in the oral cavity in recent decades have become a health problem, with factors such as an imbalance of the local microbiota being the cause for their propagation. Conventional antifungal treatments, instead of being beneficial, have generated alterations that have led to antifungal resistance. The aim of this study was to investigate and describe phytotherapy resources as a possible solution to oral antifungal resistance. A bibliographic search was carried out on platforms such as PubMed, Scopus, ScienceDirect, Web of Science, and Google scholar. A total of 248 scientific articles were obtained, of which 108 met the inclusion criteria. Microorganisms of fungal origin currently show resistance to the different antifungals of conventional use, which is undoubtedly altering the oral health of human beings, but there are new therapeutic possibilities such as the active principles of various natural species.
26 June 2024 in Journal of Drug Delivery Science and Technology
A pharmaceutical vehicle based on lyophilized liposomes is proposed for the buccal administration of drugs aimed at systemic delivery through the sublingual mucosa. Liposomes made of egg phosphatidylcholine and cholesterol (7/3 molar ratio) were prepared and lyophilized in the presence of different additive mixtures with mucoadhesive and taste-masking properties. Palatability was assayed on healthy volunteers. The lyophilization cycle was optimized, and the lyophilized product was compressed to obtain round and capsule-shaped tables that were evaluated in healthy volunteers. Tablets were also assayed regarding weight and thickness uniformities, swelling index and liposome release. The results proved that lyophilized liposomes in unidirectional round tablets have palatability, small size, comfortability and buccal retention adequate for sublingual administration. In contact with water fluids, the tablets swelled, and rehydrated liposomes were released at a slower rate than permeation efficiency determined using a biomimetic membrane. Permeability efficiency values of 0.72 ± 0.34 µg/cm2/min and 4.18 ± 0.95 µg/cm2/min were obtained for the liposomes with and without additives, respectively. Altogether, the results point to the vehicle proposed as a liposomal formulation suitable for systemic drug delivery through the sublingual mucosa.
1 August 2017 in European Journal of Pharmaceutical Sciences