Unlike 2-hydroxyprimaquine, 3- and 4-hydroxyprimaquine were formed more readily from (−)-PQ than in (+)-PQ (2:1 and 5:1, respectively) (Fig. 3). Both 3-hydroxy- and 4-hydroxyprimaquine have sharp early rises, which were again completely suppressed by CQ and QN at the early stages, then appearing in limited amounts after 5 min. The inhibitory effect of QN on the formation of the monohydroxyprimaquines appeared to be slightly more than the equimolar CQ, but the two were generally comparable. Both CQ and QN completely suppressed the formation of the 5,6-orthoquinone (Fig. 4), presumptively derived from 5-hydroxyprimaquine. Both CQ and QN show only moderate inhibition on CYP2D6-catalyzed formation of the PQ terminal alcohol. Interestingly, in contrast to the effect on ring-hydroxylated metabolites, CQ caused greater inhibition (about 70 %) of CYP2D6-mediated formation of PQ alcohol from (+)-PQ while QN caused only about 45 % inhibition, respectively (Fig. 5).Fig. 3The influence of chloroquine and quinine on the CYP2D6-mediated formation and kinetics of 3-hydroxyprimaquine from racemic PQ (a) and its individual enantiomers (b, c); and on the formation of 4-hydroxyprimaquine from racemic PQ (d) and its enantiomers (e, f). Each point represents values mean ± S.D. (n = 4)Fig. 4The inhibitory effect of chloroquine and quinine on the formation and time-course of the PQ 5,6-orthoquinone generated from racemic PQ (a) and its individual enantiomers (b, c) by CYP2D6; and on the formation of primaquine alcohol from CYP2D6-catalyzed metabolism of racemic PQ (d) and its enantiomers (e, f). Each point represents values mean ± S.D. (n = 4)Fig. 5Comparative depletion of racemic PQ (a) and its enantiomers (b, c) on incubation with recombinant human monoamine oxidase; and the formation of PQ alcohol (d–f) from racemic PQ (d) and its enantiomers (e, f) by the same enzyme. Each point represents values mean ± S.D. (n = 4)