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Pharmacokinetic study of the oral fluorouracil antitumor agent S-1 in patients with impaired renal function.
- Source :
-
Cancer science [Cancer Sci] 2019 Jun; Vol. 110 (6), pp. 1987-1994. Date of Electronic Publication: 2019 May 11. - Publication Year :
- 2019
-
Abstract
- Although dose reduction of S-1 is recommended for patients with impaired renal function, dose modification for such patients has not been prospectively evaluated. The aim of the present study was to investigate the pharmacokinetic parameters of 5-fluorouracil, 5-chloro-2,4 dihydroxypyridine and oteracil potassium, and to review the recommended dose modification of S-1 in patients with renal impairment. We classified patients receiving S-1 into 4 groups according to their renal function, as measured using the Japanese estimated glomerular filtration rate (eGFR) equation. The daily S-1 dose was adjusted based on the patient's eGFR and body surface area. Blood samples were collected for pharmacokinetic analysis. A total of 33 patients were enrolled and classified into 4 groups as follows: 10 patients in cohort 1 (eGFR ≥ 80 mL/min/1.73 m <superscript>2</superscript> ), 10 patients in cohort 2 (eGFR = 50-79 mL/min/1.73 m <superscript>2</superscript> ), 10 patients in cohort 3 (eGFR = 30-49 mL/min/1.73 m <superscript>2</superscript> ), and 3 patients in cohort 4 (eGFR < 30 mL/min/1.73 m <superscript>2</superscript> ). Those in cohorts 3 and 4 treated with an adjusted dose of S-1 showed a similar area under the curve for 5-fluorouracil (941.9 ± 275.6 and 1043.5 ± 224.8 ng/mL, respectively) compared with cohort 2 (1034.9 ± 414.3 ng/mL). Notably, while there was a statistically significant difference between cohort 1 (689.6 ± 208.8 ng/mL) and 2 (P = 0.0474) treated with an equal dose of S-1, there was no significant difference observed in the toxicity profiles of the cohorts. In conclusion, dose adjustment of S-1 in patients with impaired renal function using eGFR is appropriate and safe.<br /> (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Subjects :
- Administration, Oral
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols adverse effects
Antineoplastic Combined Chemotherapy Protocols pharmacokinetics
Area Under Curve
Cohort Studies
Drug Combinations
Female
Fluorouracil administration & dosage
Fluorouracil adverse effects
Fluorouracil pharmacokinetics
Glomerular Filtration Rate drug effects
Humans
Male
Middle Aged
Nausea chemically induced
Oxonic Acid administration & dosage
Oxonic Acid adverse effects
Oxonic Acid pharmacokinetics
Renal Insufficiency complications
Renal Insufficiency metabolism
Stomach Neoplasms complications
Stomach Neoplasms metabolism
Tegafur administration & dosage
Tegafur adverse effects
Tegafur pharmacokinetics
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Renal Insufficiency drug therapy
Stomach Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1349-7006
- Volume :
- 110
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cancer science
- Publication Type :
- Academic Journal
- Accession number :
- 30989775
- Full Text :
- https://doi.org/10.1111/cas.14025