- Japanese Society of Drug Informatics
- 医薬品情報学 (ISSN:13451464)
- vol.17, no.4, pp.175-184, 2016 (Released:2016-03-19)
Objective: To evaluate the validity of dosage adjustment of renally eliminated drugs using Giusti and Hayton method in patients with renal dysfunction by reviewing the pharmacokinetic data of the drugs.Design: A systematic literature review.Methods: Drugs with the following characteristics: ≥70% of the drug excreted in urine is the unchanged form and ≥20% of the drug in plasma is the unbound drug, were retrieved from Goodman and Gilman’s the Pharmacological Basis of Therapeutics, 12th edition. For the drugs identified, the area under the concentration-time curves (AUC) obtained from pharmacokinetic studies in healthy subjects and patients with renal dysfunction were extracted from package inserts, interview forms, summary basis of approval, and by systematic review of the MEDLINE database. Pharmacokinetic studies in children, patients with end-stage renal disease, patients on hemodialysis, and kidney transplanted patients were excluded from this review. The observed AUC ratio (AUCRobserved) of a drug was calculated by dividing mean AUC of patients by that of healthy subjects, and stratified by creatinine clearance (CLcr) into three categories: 50 to 79 mL/min, 30 to 49 mL/min, and 10 to 29 mL/min. Theoretical AUC ratios (AUCRpredicted) of drugs for the respective CLcr categories were calculated using Giusti and Hayton method.Results: Twenty-six drugs met our study criteria, and 43 data sets were obtained from the data sources. The AUCRobserved deviated from the AUCRpredicted by more than ±50% in 3 of 35 (9%) data sets for CLcr 50 to 79 mL/min, 4 of 39 (10%) data sets for CLcr 30 to 49 mL/min, and 7 of 29 (24%) data sets for CLcr 10 to 29 mL/min.Conclusion: Since AUCRpredicted calculated by Giusti and Hayton method erratically over- or under-estimates the maintenance doses in patients with reduced renal function, the use of AUCRobserved is preferred for dose adjustment in these patients.