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. 2016 Feb 2;5(2):65–73. doi: 10.1002/psp4.12058

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© 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

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Composite model describing the plasma PK of ribavirin, its intracellular phosphorylation kinetics, and effect of RTP on RBC turnover. CL_t, total clearance. V_c, central compartment volume of distribution. CL_d, distributional clearance. V_p, peripheral compartment volume of distribution. k_a: absorption rate constant. k_mp, transport/formation rate constant for ribavirin monophosphate (RMP); k_mpout, rate constant for the disappearance of phosphorylated ribavirin. R_dpmp, rapid equilibrium partition coefficient between ribavirin diphosphate (RDP) and RMP; R_tpdp, rapid equilibrium partition coefficient between ribavirin triphosphate (RTP) and RDP; R_in, zero‐order hemoglobin production rate; k_out, rate constant for RBC elimination (inverse of RBC lifespan); k_RTP, effect of RTP concentration in RBC on RBC lifespan; γ, feedback term characterizing RBC production rate increase in response to anemia.