Fig. 3

Pharmacological interactions between primaquine and fluoxetine. a Fluoxetine-mediated complete inhibition of primaquine metabolism by CYP 2D6 in vitro. Shown is the time course of primaquine CYP 2D6 metabolism alone (blue line), or upon fluoxetine pre-treatment (red line). The error shown is from duplicate experiments. b Liver Cmax values from pharmacokinetic analysis of the CYP 2D6-dependent primaquine metabolite 5,6-ortho-quinone from mice given a single primaquine dose (20 mg/kg, blue bar), or mice given a single primaquine dose (20 mg/kg) with fluoxetine (12 mg/kg daily for 3 days, see “Methods” section, red bar). The error shown is from triplicate pharmacokinetic analyses. c Average per cent parasitaemia measurements from flow cytometry measurement for the infection control group (black line), primaquine + fluoxetine (PQ + FLX)-treated mice (red line), and primaquine alone -treated mice (PQ, blue line). d Anti-malarial efficacy of primaquine in a prophylaxis mouse malaria model. The per cent survival of mice infected with P. berghei is shown for the different treatment groups. Mice infected and not given any anti-malarial drug are shown by the black line (0/5 survived duration of experiment). Mice infected and given primaquine at the ED₁₀₀ are shown by the blue line (5/5 survived duration of experiment). Mice infected and given primaquine at the ED₁₀₀ along with concurrent fluoxetine administration are shown by the red line (1/5 survived duration of experiment). Five mice were used per group for efficacy experiments