Expert opinion on drug metabolism & toxicology · 2026
Pharmacokinetics of novel drugs for the treatment of diabetic nephropathy.
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Mousavi Taraneh, Shaya Fadia T, Munir Kashif M, Davis Stephen N
Аннотация
INTRODUCTION: Diabetic kidney disease (DKD) alters drug pharmacokinetics (PK), affecting exposure, pharmacodynamic response, and toxicity. As newer therapies become central to DKD management, understanding their PK profiles is essential for individualized treatment across stages of kidney impairment.
AREAS COVERED: PubMed/MEDLINE, Embase, and Scopus were searched from database inception through 18 April 2026, for evidence on PK, pharmacodynamics, renal-impairment effects, and drug-drug interactions. Evidence was synthesized for sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), dual incretin agonists, nonsteroidal mineralocorticoid receptor antagonists (nsMRA), endothelin receptor antagonists (ERA), aldosterone synthase inhibitors (vicadrostat, baxdrostat, and lorundrostat), avenciguat, and ziltivekimab, emphasizing exposure, clearance, metabolism, elimination, and dosing implications.
EXPERT OPINION: In reduced kidney function, SGLT2i show modest increases in drug exposure but attenuated glucose-lowering effects. Finerenone demonstrates modest exposure increases despite minimal renal clearance. Some ERAs, particularly zibotentan may have larger esposure increases, poentially narrowing the therapeutic window. Newer incretin-based therapies generally maintain stable exposure. However, eGFR alone may not fully capture changes in drug disposition. Factors such as uremia, altered protein binding, and nonrenal clearance can also affect exposure. The next advance will likely be drug-specific decision support integrating eGFR trajectory, potassium levels, dialysis status, body composition, and concomitant medications, rather than universal therapeutic drug monitoring.
AREAS COVERED: PubMed/MEDLINE, Embase, and Scopus were searched from database inception through 18 April 2026, for evidence on PK, pharmacodynamics, renal-impairment effects, and drug-drug interactions. Evidence was synthesized for sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), dual incretin agonists, nonsteroidal mineralocorticoid receptor antagonists (nsMRA), endothelin receptor antagonists (ERA), aldosterone synthase inhibitors (vicadrostat, baxdrostat, and lorundrostat), avenciguat, and ziltivekimab, emphasizing exposure, clearance, metabolism, elimination, and dosing implications.
EXPERT OPINION: In reduced kidney function, SGLT2i show modest increases in drug exposure but attenuated glucose-lowering effects. Finerenone demonstrates modest exposure increases despite minimal renal clearance. Some ERAs, particularly zibotentan may have larger esposure increases, poentially narrowing the therapeutic window. Newer incretin-based therapies generally maintain stable exposure. However, eGFR alone may not fully capture changes in drug disposition. Factors such as uremia, altered protein binding, and nonrenal clearance can also affect exposure. The next advance will likely be drug-specific decision support integrating eGFR trajectory, potassium levels, dialysis status, body composition, and concomitant medications, rather than universal therapeutic drug monitoring.