Drug Development Perspective on Pharmacokinetic Studies of New Drugs in Patients With Renal Impairment

Severe renal impairment can, through diverse mechanisms, alter the pharmacokinetics (PK) of drugs that are renally eliminated and even of some drugs that are nonrenally eliminated. Consequently, dose adjustment for new molecular entities in patients with renal insufficiency is a critical issue in drug development. Clinical pharmacology studies undertaken in patients with renal impairment are generally quite small. We therefore recommend that all pertinent pharmacokinetic data relating to subjects with different degrees of renal impairment and from different clinical trials, including population pharmacokinetic evaluation, form the basis for dosage recommendations in renal impairment. The Modification of Diet in Renal Disease (MDRD) equation has gained popularity for renal insufficiency classification, but traditional equations such as the Cockcroft-Gault (C-G) formula should enjoy continued use so as to avoid confusion, particularly for drugs for which dosing guidelines have previously been developed.