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The Influence of Renal Function on Hydroxyurea Pharmacokinetics in Adults With Sickle Cell Disease
Author(s) -
Yan JingHe,
Ataga Kenneth,
Kaul Sanjeev,
Olson Jeffery S.,
Grasela Dennis M.,
Gothelf Samantha,
Kutlar Abdulah,
Orringer Eugene
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270004273526
Subject(s) - medicine , pharmacokinetics , renal function , dosing , end stage renal disease , kidney disease , urinary system , effective renal plasma flow , urology , gastroenterology , disease , renal blood flow
This was an open‐label, nonrandomized, 2‐center study conducted to assess the influence of renal function on the pharmacokinetics of hydroxyurea in adults with sickle cell disease (SCD). Seventeen patients were divided into 5 groups: normal renal function (n = 7), mild renal impairment (n = 2), moderate renal impairment (n = 3), severe renal impairment (n = 2), and end‐stage renal disease (ESRD, n = 3). Except for patients with ESRD, all the patients received a 15‐mg/kg single oral dose of hydroxyurea. Patients with ESRD received a 15‐mg/kg oral dose of hydroxyurea on 2 occasions. Blood and urine samples were collected for the assessment of hydroxyurea pharmacokinetics. The results indicate that the systemic exposure increases and the urinary recovery decreases as the degree of renal insufficiency worsens. On the basis of the exposure and the apparent clearance from the current and 2 historical studies, the authors have proposed an initial dosing regimen of hydroxyurea (7.5 mg/kg/day) for SCD patients with CL cr <60 mL/min. This dosing strategy is anticipated to provide a safe dose for SCD patients with renal impairment.