Potential pharmacokinetic interactions of therapeutic cytokines or cytokine modulators on small-molecule drugs: mechanistic understanding via studies using in vitro systems.
The potential pharmacokinetic interactions between macromolecules and small-molecule drugs have received more and more attention with the increasing development of macromolecule therapeutics. Studies have shown that cytokines can differentially modulate drug-metabolizing enzymes and transporters, which raises concerns on the potential interactions of therapeutic cytokines and cytokine modulators on the disposition of small-molecule drugs. Although many in vitro studies have been conducted to characterize the effects of cytokines on drug-metabolizing enzymes and transporters, these studies were limited to only a handful of cytokines, such as interleukin-1 (IL-1), IL-6, tumor necrosis factor-α, and interferon. It is also challenging to translate these in vitro results to in vivo. In addition, information on the impact of cytokine modulators on drug-metabolizing enzymes and transporters is rather limited. More research is needed in this area. The present review is to provide a summary of the in vitro findings on the pharmacokinetic interactions of therapeutic cytokines and cytokine modulators on small-molecule drugs. Discussion on current challenges in assessing these interactions is also included.
Jin
J
Zhou
Feng
F
Li
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004347:Drug Interactions / Q000502:physiology*; D005982:Glutathione Transferase / Q000502:physiology; D006801:Humans; D007728:Kupffer Cells / Q000502:physiology; D046911:Macromolecular Substances / Q000493:pharmacokinetics; D026901:Membrane Transport Proteins / Q000502:physiology
D016207:Cytokines; D046911:Macromolecular Substances; D026901:Membrane Transport Proteins; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase