Systematic Analysis of Changes in Drug Exposure in Patients with Renal Dysfunction and Their Relationships with Renal Excretion Ratio of the Drug

Abstract

We investigated the relationships between the renal excretion ratio (RR) and changes in drug exposure in patients with renal dysfunction (RD), to examine the usefulness of RR in determining the optimal dosage for patients with renal dysfunction. The area under the plasma concentration time curve ratios (AUC ratios: AUCRs = AUCRD /AUCNormal ) of 52 out of 70 drugs was observed within 67-150％ of the theoretical values calculated by the Giusti-Hayton method using the RR value. It was confirmed that the RR is useful for determining the optimal dosage of extensively renally excreted drugs for patients with RD. However, it should be noted that the AUCRs were more than 150 ％ of the theoretical value for some orally administrated drugs that are excreted renally but less extensively. Especially, for substrates of OATP1B1 or OATP1B3, the AUCRs of four out of five drugs were more than 150％. Substrates of metabolizing enzymes and other transporters showed less relevance in this regard. Key