The uridine diphosphate glucuronosyltransferase (UGT) 1A1 and 1A9 isoforms are 
involved in the phase II biotransformation of the irinotecan metabolite, SN-38. 
Recently, several variants in the UGT1A1 and UGT1A9 genes have been described 
with altered functionality in vitro. The aim of this study was to evaluate the 
functional consequence of the UGT1A1(TA)(7)TAA (UGT1A1(*)28), UGT1A9 766G>A 
(D256N; UGT1A9(*)5), and UGT1A9 98T>C (M33T; UGT1A9(*)3) variants in Caucasian 
patients treated with irinotecan. Pharmacokinetic studies were performed after 
the first course of irinotecan in 47 males and 47 females. The mean (SD) area 
under the curves (AUCs) of irinotecan and SN-38 were 20,348 +/- 6466 ng x h/mL 
and 629 +/- 370 ng x h/mL, respectively, which is in line with earlier findings. 
For UGT1A9(*)5,novariant alleles were observed, whereas for UGT1A9(*)3, 1 
patient with the variant allele was found (allele frequency, 0.633%). The 
distribution of the UGT1A1(*)28 variant showed 44 wild-type patients (Wt), 37 
heterozygotes (Het), and 5 homozygotes (Var). The median AUC ratio of SN-38G to 
SN-38 was significantly reduced in carriers of the variant UGT1A1(*)28 allele 
(7.00 [Wt] vs. 6.26 [Het] vs. 2.51 [Var]; p =.022). It is concluded that UGT1A9 
functional variants are rare in Caucasians and likely to be clinically 
insignificant in irinotecan regimens. Screening for the UGT1A1(*)28 polymorphism 
may identify patients with altered SN-38 pharmacokinetics.