Mj. Moore et al., DEVELOPMENT AND VALIDATION OF A LIMITED SAMPLING STRATEGY FOR 5-FLUOROURACIL GIVEN BY BOLUS INTRAVENOUS ADMINISTRATION, Therapeutic drug monitoring, 15(5), 1993, pp. 394-399
A wide range of interindividual variability of 5-fluorouracil (5-FU) p
harmacokinetics exists after bolus administration. The degree to which
this variability in 5-FU exposure impacts upon the response and toxic
ity of the drug has not been determined. The area under the concentrat
ion time curve (AUC) is a commonly used indicator of exposure, but nor
mally requires the collection of 8-10 timed blood samples after i.v. b
olus administration. This presents difficulties if large-scale populat
ion samplings are required. This study involved the development and te
sting of a strategy to estimate AUC from a limited number of blood sam
ples in patients with gastrointestinal and breast cancer. The optimal
single time point for AUC estimation was 0.17 h (r2 = 0.954). Addition
of the 0.75 h time point significantly improved predictability (r2 =
0.983). Addition of a third or fourth time point did not provide furth
er benefit. These models were then tested separately in a group of wom
en who received a higher dose of 5-FU. The two data points model perfo
rmed significantly better than the single time point model (r2 = 0.70
and 0.85, respectively). The AUC of standard dose 5-FU after bolus adm
inistration can be reliably estimated from two timed samples taken 10
and 45 min after injection.