Clinical Pharmacology – Chemical
2019 PharmSci 360
Chronic Kidney Disease (CKD) leads to impaired renal function and is becoming an increasing global health burden. Altered drug exposure, efficacy, toxicity can result from disturbances in renal function, particularly for drugs that are primarily renally eliminated, but may also impact on drugs in which hepatic clearance is dominant. The mechanistic aspects resulting in the altered hepatic clearance are not fully understood. It is also unclear as to whether studies involving CKD patients should be undertaken. The presentation describes utilizing cohorts of clinical studies, containing focusing on CYP450s and OATPs in healthy and differing severity CKD patients, in order to provide general rules concerning the need to conduct clinical studies for non-renally eliminated drugs. Undertaking reverse translational studies such as this and incorporating activity changes into mechanistic PBPK models can provide quantitative prediction of CKD effects.