Correlation of CYP2D6 polymorphisms and pharmacokinetics of primaquine in thai army population on the Thailand-Cambodia border area

The antimalarial drug primaquine (PQ), which has minimal activity, has to be metabolized through the CYP2D6 enzyme for its most effective antimalarial activity. The stable form 5,6-orthoquinone-primaquine (5,6-PQ) was used as a representative marker for PQ active metabolite quantification. However, the relationship between CYP2D6 polymorphisms and the pharmacokinetic (PK) parameters of 5,6-PQ has not been reported. We assessed the relationship between CYP2D6 polymorphisms and PKs of both PQ and 5,6-PQ in the Thai army population on the Thailand-Cambodia border area. We found that 56% of volunteers were CYP2D6 normal metabolizers (CYP2D6 NMs) and 44% were CYP2D6 intermediate metabolizers (CYP2D6 IMs). Although most of the PK parameters of PQ in plasma between phenotypes were similar, the amount excreted of urine PQ during the last 12 hours after PQ administration was 65% higher in CYP2D6 IMs compared with CYP2D6 NMs (p