Population Pharmacokinetic and Exposure–Response Analysis of Weekly Teriparatide in Osteoporosis Patients

Abstract Teriparatide is a potent therapeutic agent for the treatment of osteoporosis. One of the aims of this analysis was to develop a population pharmacokinetic (PPK) model to understand the pharmacokinetic characteristics of the once‐weekly formulation of teriparatide. Another aim was to develop an exposure–response model to describe the relationship between change in bone mineral density (BMD) and teriparatide exposure after weekly subcutaneous administration. The PPK analysis showed that apparent total body clearance was significantly influenced by estimated creatinine clearance and the presence of osteoporosis. A data set consisting of lumbar spine BMD values for 513 osteoporosis patients whose area under the concentration–time curve (AUC) of teriparatide acetate was estimated by the developed PPK model was then compiled. Exposure–response analysis showed that the percentage change from baseline of BMD was well described by a function of the AUC of teriparatide acetate, time, and coadministration of alfacalcidol and a calcium preparation. The analysis indicated that AUC is an important parameter for predicting BMD response to once‐weekly teriparatide in osteoporosis patients.