Table 1. Effects of pirfenidone in animal models of lung, heart, kidney, and liver fibrosis
SystemReferenceIn vivo modelSpeciesProtocolTotal daily dose/routeFibrosisFibrotic markersInflammatory markersOxidative stressFunctional end-points
LungOku et al. [38]BleomycinMouseProphylactic10, 30*, 100* mg·kg−1 p.o.#DecreasedDecreasedDecreasedNANA
H. Oku; personal communicationBleomycinMouseTherapeutic10, 30*, 100* mg·kg−1 p.o.#DecreasedNANANANA
Kakugawa et al. [39]BleomycinMouseTherapeutic400* mg·kg−1 p.o.DecreasedDecreasedNANANA
Iyer et al. [40]BleomycinHamsterProphylactic0.5%* in chowDecreasedDecreasedNADecreasedNA
Iyer et al. [41]BleomycinHamsterTherapeutic+0.5%* in chowDecreasedDecreasedNADecreasedNA
Iyer et al. [42]BleomycinHamsterProphylactic0.5%* in chowDecreasedDecreasedNADecreasedNA
Gurujeyalakshmi et al. [43]BleomycinHamsterProphylactic0.5%* in chowNADecreasedNANANA
Schelegle et al. [44]BleomycinHamsterProphylactic0.5%* in chowDecreasedNANANAImproved
Liu et al. [45]TransplantRatProphylactic0.5%* in chowDecreasedDecreasedNANo effectImproved
Zhou et al. [46]1) TransplantRatProphylactic0.5%* in chowDecreasedDecreasedNANANA
2) TransplantRatTherapeutic0.5% in chowNo effectNANANANA
Hirano et al. [47]Allergen induced dysfunctionMouseProphylactic125, 250, 500* mg·kg−1 s.c.§DecreasedDecreasedDecreasedNAImproved
HeartLee et al. [2]Congestive heart failureDogProphylactic2400* mg p.o.#DecreasedDecreasedDecreasedNAImproved
Nguyen et al. [3]MIRatTherapeutic1.2%* in chowDecreasedNANANAImproved
Mirkovic et al. [33]HypertensionRatTherapeutic0.4%* in chowDecreasedNANANAImproved
KidneyShimizu et al. [48]1) Continuous ureteral obstructionRatProphylactic0.6–0.9%* in chowDecreasedDecreasedNANANA
2) Continuous ureteral obstructionRatTherapeutic0.6–0.9%ƒ in chowTrendDecreasedNANANA
3) Temporary ureteral obstructionRatTherapeutic0.6–0.9%* in chowDecreasedNANANAImproved
Takakura et al. [49]5/6 nephrectomyRatTherapeutic1%* in chowDecreasedDecreasedNANATrend
Shimizu et al. [50]5/6 nephrectomyRatTherapeutic0.6–0.9%* in chowDecreasedDecreasedNANAImproved
RamachandraRao et al. [51]Diabetic db/dbMouseTherapeutic0.5%* in chowDecreasedDecreasedNANANo effect
LiverSalazar-Montes et al. [52]1) Carbon tetrachlorideRatTherapeutic200ƒ mg·kg−1 p.o.§TrendDecreasedNADecreasedImproved
2) Bile duct ligationRatTherapeutic200* mg·kg−1 p.o.§DecreasedDecreasedNADecreasedNo effect
Garcia et al. [53]1) Carbon tetrachlorideRatTherapeutic##500* mg·kg−1 p.o.DecreasedDecreasedNANAImproved
2) Carbon tetrachlorideRatTherapeutic¶¶200* mg·kg−1 p.o.§DecreasedNANANANA
3) Bile duct ligationRatProphylactic200*, 500 mg·kg−1 p.o.§DecreasedNANANANA
Di Sario et al. [54]DimethylnitrosamineRatTherapeutic0.5%* in chowDecreasedDecreasedDecreasedNAImproved
Tada et al. [55]DimethylnitrosamineRatProphylactic500* mg·kg−1 p.o.§DecreasedTrendNANANo effect

  • NA: not assessed; MI: myocardial infarction. *: statistically significant treatment effect (per reference); #: given in three divided daily doses; : given in two divided daily doses; +: pirfenidone treatment initiated following the second of three bleomycin insults; §: given in one daily dose; ƒ: treatment-associated trend; ##: pirfenidone dosed following cessation of carbon tetrachloride; ¶¶: pirfenidone dosed in final 3 weeks of an 11-week model with continuous carbon tetrachloride.