Abstract:
Aims: Dihydropyrimidine dehydrogenase (DPD) reduces endogenous pyrimidines and therapeutic analogues such as the anticancer agent 5-fluorouracil (SFU). Among Caucasian populations DPD activity is highly variable and subject to polymorphic regulation. To evaluate interethnic influence, DPD activity was assessed in South-west Asian, Kenyan and Ghanaian populations. Methods: DPD activity was determined in peripheral mononuclear cells using [14C]-5-fluorouracil and h.p.l.c. analysis. Results: A high degree of variation in DPD activity was observed within each population (range CV=34-48%). Median DPD activity also varied between these populations. South-west Asian and Kenyan subjects exhibited almost identical median values (192 and 193.5 pmol min-1 mg-1, respectively), which were similar to Caucasians (median 215 pmol min-1 mg-1). A significantly lower median DPD activity (119 pmol min-1 mg-1) was observed in the Ghanaian population. Conclusions: The similarity in DPD activity between Caucasian, Kenyan and South-west Asian populations suggests that the incidence of 5FU-related toxicity may be comparable in these groups. The pharmacokinetic implications of lower activity amongst Ghanaians needs to be evaluated.