A phase I trial of flavopiridol administered as a 1-h i.v. infusion schedule was explored. Fifty-five patients were treated with flavopiridol at doses ranging from 12 to 78 mg/m2daily for 5, 3 and 1 day every 3 weeks. Pharmacokinetic and pharmacodynamic analysis was performed together with analysis of a promoter polymorphism of theUGT1A1gene. Peak concentrations and areas under the time–concentration curve of flavopiridol were linear within the doses studied. Estimated clearance was 13.8±4.9 l/h/m2(mean±SD), volume of distribution at steady-state was 64.9±43.4 l/m2and elimination half-life was 5.2±4.9 h. Forty-nine of the 55 patients were genotyped for the promoter polymorphism. We found five (10%) homozygous and 11 (22%) heterozygous patients forUGT1A1*28, which alters the reference sequence (TA)6TAA to the variant (TA)7TAA by an extra TA dinucleotide insertion within the TATA box. One patient was heterozygous for the sequence of five TA repeats, (TA)5TAA. The remaining 32 patients did not have theUGT1A1*28allele (homozygous for the reference sequence). Associations of theUGT1A1promoter genotype with either the pharmacokinetic parameters or diarrhea (occurrence and severity) were not observed in this study. The pharmacogenetic analyses did not support that theUGT1A1promoter polymorphism could affect flavopiridol pharmacokinetics and alter the incidence and severity of diarrhea induced by the drug.