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Pharmacokinetics of FK506 After Intravenous and Oral Administration in Patients Awaiting Renal Transplantation
Author(s) -
Gruber Scott A.,
Hewitt Jeanne M.,
Sorenson Amy L.,
Barber Donald L.,
Bowers Larry,
Rynders Greg,
Arrazola Luis,
Matas Arthur J.,
Rosenberg Mark E.,
Canafax Daniel M.
Publication year - 1994
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 - 10.1002/j.1552-4604.1994.tb02052.x
Subject(s) - pharmacokinetics , dosing , medicine , crossover study , bioavailability , oral administration , transplantation , blood sampling , volume of distribution , half life , pharmacology , urology , anesthesia , alternative medicine , pathology , placebo
The authors examined the safety and pharmacokinetics of FK506, a new hepatically metabolized immunosuppressant, after single‐dose intravenous (IV) infusion (20 μg · kg −1 · 4 hours −1 ) and oral (80 μg/kg) administration in six nondialysis patients, aged 27 to 53 years, with chronic renal failure awaiting transplantation. A two‐period, randomized, crossover study protocol was used with blood samples drawn for 72 hours after each dose and a washout period of 4 days. Whole‐blood FK506 levels were determined using a standard, two‐step, nonspecific enzyme immunoassay. There were no significant changes in vital signs, EKG, or complete laboratory test battery for any patient during the entire study period. No side effects were noted after IV or oral FK506 dosing. Mean ± SD distribution half life was 0.9 ± 0.2 hours, elimination half life (t 1/2β ) 33 ± 8 hours, total body clearance (CL) 2.4 ± 1.1 L/hour, and bioavailability 14 ± 12%. There was no significant correlation between serum creatinine (Cr) and CL (r = 0.36) or between Cr and t 1/2β (r = −0.30). It was found that FK506 is incompletely and erratically absorbed after oral administration and is rapidly distributed outside the blood compartment after IV dosing. An extended sampling period seems necessary to accurately characterize the slow elimination phase of FK506 .