Pharmacokinetics of tofacitinib, a janus kinase inhibitor, in patients with impaired renal function and end-stage renal disease

We investigated the pharmacokinetics of non-metabolized cefotaxime in 10 patients undergoing CAPD. The elimination half-life after IV administration of I g cefotaxime was 3.1 ± 1.3 hr, i.e. two to three times longer than in individuals with normal renal function but similar to patients with severe renal insufficiency. An average of 2.18% of the dose was recovered in the effluent. The halflife of I g cefotaxime administered in the dialysis solutions was 1.4 ± 0.8 hr. This difference between the half-lives after intraperitoneal and intravenous administration indicates a faster transport through the peritoneal membrane. Intraperitoneally administered cefotaxime -250 mg four times daily, was effective in the treatment of peritonitis in three CAPD patients. Since its introduction in 1976, CAPD has become an effective therapy for end-stage renal disease. The most serious complication is peritonitis and effective treatment is essential. Cefotaxime, a new broad-spectrurn cephalosporin, is active against most gramnegative and gram-positive organisms. It possesses no nephrotoxicity and may be useful in the treatment of peritonitis and other infections in patients on CAPD. This study was done to evaluate the pharmacokinetics of cefotaxime administered intravenously and intraperitoneally during CAPD.

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Gilteritinib administration in a hemodialysis patient

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220973259 ◽

2020 ◽

pp. 107815522097325

Author(s):

Eris Tollkuci ◽

Tiffany Tran ◽

Rebecca Myers

Keyword(s):

Renal Disease ◽

Tyrosine Kinase ◽

End Stage Renal Disease ◽

Kinase Inhibitor ◽

Severe Renal Impairment ◽

Human Subjects ◽

Single Agent ◽

Cyp3a4 Enzyme ◽

Stage Renal Disease ◽

End Stage

Introduction Gilteritinib is a multitargeted tyrosine kinase inhibitor (TKI) approved by the Food and Drug Administration (FDA) for acute myeloid leukemia (AML) with a FMS-related tyrosine kinase 3 (FLT3) mutation. The pharmacokinetics of gilteritinib in the setting of severe renal impairment (creatinine clearance [CrCl] 15-29 mL/min utilizing Cockcroft-Gault method) and end-stage renal disease are unknown. Gilteritinib is primarily metabolized by the liver through the CYP3A4 enzyme and is eliminated in both the feces and urine. Its excretion is primarily through the fecal route, accounting for 64.5% of the recovered dose. Only about 16.4% of the recovered dose has been detected in the urine of human subjects. Case Report We describe our patient case documenting the administration of gilteritinib in the setting of end-stage renal disease (ESRD) and hemodialysis (HD). Management and Outcomes: Our patient was initiated on single agent gilteritinib 120 mg by mouth once daily for relapse FLT3-TDK positive AML. Treatment course was complicated by pancytopenia, neutropenic fever, and staphylococcus lugdunensis bacteremia requiring temporary interruption of therapy. Discussion Given that gilteritinib is metabolized by the liver and eliminated primarily in the feces, one does not expect an increase in toxicity related to impaired renal function. Although this report describes the successful utilization of gilteritinib, caution should be exercised when administering in patient populations with end organ disease, and patient comorbidities should be taken into account.

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