Lais

Long‐acting injectable medicinal products (LAIs) prolong drug release and thereby aim to enhance adherence and patient outcomes. European regulatory guidelines require the conduct of single‐ and multiple‐dose trials to exclude differences in drug release between non‐steady and steady state conditions. The complexity of these trials may however hamper the development of LAIs. This study aimed to examine whether drug release is different after single‐ and multiple‐dose administration using clinical pharmacokinetic (PK) data of a sample of five regulatory‐approved LAIs. Single‐ and multiple‐dose data were extracted from an internal regulatory database. Population pharmacokinetic models with different absorption structures were developed using nonlinear mixed‐effect modeling based on the single‐dose data of every LAI. The best‐fitting models were used to predict the pharmacokinetic profiles after multiple‐dose administration. The absorption of LAIs after single‐dose administration was best described with (parallel) first‐order absorption structures (with and without lag‐time). After multiple‐dose administration, the mean model accuracy was 93% (minimum to maximum: 70%–122%), and 7 out of 10 observed pharmacokinetic variables (i.e., area under the plasma concentration—time curve, minimum and maximum concentration) met the pre‐specified acceptance criteria. In conclusion, multiple‐dose PK characteristics can be predicted using models developed from single‐dose PK data, which indicates that drug release may not be very different between dosing conditions in this sample of regulatory‐approved LAIs. Nevertheless, additional studies on other LAIs are required to test the generalizability of our findings and to increase our understanding of the limitations of the proposed model‐based approach vis‐à‐vis the current evidentiary standard.