Conservative Long-Term Treatment of Chronic Renal Failure with Keto Acid and Amino Acid Supplementation

Tofacitinib is a Jak inhibitor developed as a treatment for rheumatoid arthritis. Tofacitinib is metabolized mainly through hepatic CYP3A1/2, followed by CYP2C11. Rheumatoid arthritis tends to increase renal toxicity due to drugs used for long-term treatment. In this study, pharmacokinetic changes of tofacitinib were evaluated in rats with gentamicin (G-ARF) and cisplatin-induced acute renal failure (C-ARF). The time-averaged total body clearance (CL) of tofacitinib in G-ARF and C-ARF rats after 1-min intravenous infusion of 10 mg/kg was significantly decreased by 37.7 and 62.3%, respectively, compared to in control rats. This seems to be because the time-averaged renal clearance (CLR) was significantly lower by 69.5 and 98.6%, respectively, due to decreased creatinine clearance (CLCR). In addition, the time-averaged nonrenal clearance (CLNR) was also significantly lower by 33.2 and 57.4%, respectively, due to reduction in the hepatic CYP3A1/2 and CYP2C11 subfamily in G-ARF and C-ARF rats. After oral administration of tofacitinib (20 mg/kg) to G-ARF and C-ARF rats, both CLR and CLNR were also significantly decreased. In conclusion, an increase in area under plasma concentration-time curves from time zero to time infinity (AUC) of tofacitinib in G-ARF and C-ARF rats was due to the significantly slower elimination of tofacitinib contributed by slower hepatic metabolism and urinary excretion of the drug.

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Effect of essential amino acid supplementation in acute renal failure

International Urology and Nephrology ◽

10.1007/bf02550090 ◽

1995 ◽

Vol 27 (4) ◽

pp. 503-510 ◽

Cited By ~ 1

Author(s):

M. Z. Mocan ◽

H. Mocan ◽

M. N. Gacar ◽

G. K. Özgür ◽

M. H. Uluutku

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

Amino Acid ◽

Essential Amino Acid ◽

Amino Acid Supplementation ◽

Acid Supplementation

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Oxaliplatin for Metastatic Colon Cancer in a Patient with Renal Failure

Clinical medicine Oncology ◽

10.4137/cmo.s412 ◽

2008 ◽

Vol 2 ◽

pp. CMO.S412

Author(s):

Kenji Katsumata ◽

Tetsuo Sumi ◽

Tatehiko Wada ◽

Yasuharu Mori ◽

Masayuki Hisada ◽

...

Keyword(s):

Colorectal Cancer ◽

Renal Failure ◽

Term Treatment ◽

Pharmacokinetic Data ◽

Metastatic Colon Cancer ◽

Standard Regimen ◽

Long Term Treatment ◽

Before And After ◽

Cecal Cancer

Objective Oxaliplatin, a key part of the standard regimen for colorectal cancer in Western countries, has become available in Japan. In a hemodialysis patient with cecal cancer, we investigated the efficacy, safety, pharmacokinetics, and dialysability of oxaliplatin. Methods A 65-year-old man who had cecal cancer was treated with oxaliplatin (40 mg/m2) and l-leucovorin(l-LV) (200 mg/m2), which were administered simultaneously over 120 min via the side and main arms of a Y-tube, respectively. Then 5-FU (400 mg/m2) was administered rapidly via the side tube, followed by 5-FU (2,000 mg/m2) over 46 hours via the main tube. The patient had chronic renal failure due to diabetic nephropathy and hemodialysis was performed 3 times a week. Blood samples were collected from the dialyzer before and after each hemodialysis session to examine platinum clearance. Results The patient received 3 courses of oxaliplatin before he died of cancer. During hemodialysis, the platinum level fell from 0.32 μg/mL to 0.15 μg/mL. Conclusion Since patients with renal failure have various associated disorders and oxaliplatin has a long half-life, it is necessary to obtain more pharmacokinetic data to investigate its accumulation and dialysability during long-term treatment. Such data will assist in treating the rapidly increasing number of hemodialysis patients with colorectal cancer.

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