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Comparison of 5‐Fluorouracil Pharmacokinetics in Whole Blood, Plasma, and Red Blood Cells in Patients with Colorectal Cancer
Author(s) -
Wattanatorn Wiboon,
McLeod Howard L.,
Macklon Fiona,
Reid Muriel,
Kendle Keith E.,
Cassidy James
Publication year - 1997
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1997.tb03778.x
Subject(s) - pharmacokinetics , medicine , whole blood , fluorouracil , colorectal cancer , folinic acid , bolus (digestion) , blood plasma , red blood cell , pharmacology , urology , cancer
Study Objective . To compare 5‐fluorouracil (5‐FU) pharmacokinetics in whole blood, plasma, and red blood cells in patients with colorectal cancer. Design . Prospective, unblinded observational study in consecutive patients. Setting . Large regional teaching hospital. Patients . Five patients with colorectal cancer. Interventions . Patients received folinic acid 200 mg/m 2 intravenously over 2 hours, followed by 5‐FU 600 mg/m 2 intravenous bolus over 30 minutes, then 5‐FU 600 mg/m 2 intravenous infusion over 22 hours, administered on days 1 and 2. This 48‐hour cycle was repeated every 14 days. Measurements and Main Results . Concentrations of 5‐FU in whole blood, plasma, and red blood cells were determined by high‐performance liquid chromatography. ADAPT II was used for pharmacokinetic computations. The optimum model was determined for each matrix by calculating Akaike's information criteria values. Concentrations of 5‐FU in whole blood were 106–115% of simultaneous plasma concentrations (median 112%), and packed red blood cell levels were 5–17% of plasma concentrations (median 11%). The drug's concentration‐time profile was similar in the three matrices. The drug is reported to be unstable in whole blood, and red blood cell 5‐FU concentrations were near the limit of detection (10 ng/ml), supporting plasma as the preferred matrix for therapeutic drug monitoring studies. Six pharmacokinetic models were fitted to the 5‐FU individual data sets to determine the best curve fit. The optimal model for whole blood and plasma data sets was one compartment with both linear and nonlinear elimination models; a one‐compartment model with nonlinear elimination provided the best curve fit for 5‐FU in red blood cells. A two‐compartment model with nonlinear elimination gave a similar degree of curve fit for plasma 5‐FU as the one‐compartment model with both linear and nonlinear elimination. Conclusions . These pharmacokinetic results provide the basis for further investigation into the ability to correlate 5‐FU systemic exposure with clinical drug activity. (Pharmacotherapy 1997;17(5):881–886)