While it is important to maintain ligand concentration at the target for a period sufficient to exert the relevant mechanism of action, it is worth noting that this period can be extremely short. Although not a polyphenol, artemisinin enjoys enormous efficacy against the malaria parasite P. falciparum with a T max at less than 2 hours and a half-life of 2-5 hours. 132,133 Also, the dosage is of utmost importance. Following due analysis of toxicity, protease inhibitors can target a C min dose (minimum concentration between consecutive doses) of many multiples of the IC50 value 134 to achieve faster viral clearance. Indirect antiviral effects of certain polyphenols may also be possible, such as non-specific upregulation of immunosurveillance, as well as modulation of specific immune cells. Also, as promiscuous binders, due attention should be applied to inhibition of liver enzymes for drug-drug interactions , especially of drugs that study subjects might concomitantly consume for the same or unrelated conditions. For example, among the polyphenols studied are those known to bind to CYP1A2 44 , CYP3A4 and OATP1A2, the latter giving rise to the famous "grapefruit effect". Conversely, this P450 or other liver enzyme inhibition may be advantageous to increase serum concentrations of verified pharmaceuticals, such as fluvoxamine, in context of combination therapy (J. Duke, personal communication, 28 Nov 2009) for superior joint bioavailability.