TABLE 13

Compilation of DRT data analyses in the literature

Experimental AreaTest CompoundRouteBiophase ParameterReason for DRTReference
AChE inhibition by SarinAdenosine A1 agonists.c., i.m.First-order input/outputNo exposure dataBueters et al. (2003)
AnemiaInduced by ribavirinp.o.First-order outputNo exposure dataTod et al. (2005)
EPOs.c.Fast EPO exposureUehlinger et al. (1992), Port et al. (1998)
AntiarrhythmicsAmiodaronei.v. bolus infusionFirst-order input/outputNo exposure dataSalem et al. (2016)
p.o.
AnticoagulantsWarfarinp.o.First-order input/outputSparse exposureHamberg et al. (2010, 2013), Wright and Duffull (2011)
p.o.First-order input/outputNo exposure dataKim et al. (2015), Ooi et al. (2017)a
AntidepressantsClomipramine, lithiump.o.First-order input/outputNo exposure dataGruwez et al. (2007)
Paroxetine, pindololp.o.First-order outputNo exposure dataGruwez et al. (2005)
TC-1734s.c.First-order input/outputUtility of DRTGatto et al. (2004)
AntilipolyticNiAci.v. infusionFirst-order outputUtility of DRTIsaksson et al. (2009), Gabrielsson and Weiner (2010), Andeon et al. (2016)
i.v. infusion, p.o.Michaelis–Menten input (p.o.)/first-order outputUtility of DRT
AntinociceptiveMorphinei.v. infusionFirst-order outputNo exposure dataAbou Hammoud et al. (2009)a
Experimental drugi.v. infusion, s.c.First-order input/output, biophase availabilityUtility of DRTGabrielsson et al. (2000), Gabrielsson and Peletier (2014)
ArthritisFosdagrocorat, prednisonep.o.First-order outputNo PDN exposureShoji et al. (2017)a
CNS stimulantDexamphetaminei.p.Utility of DRTGabrielsson and Weiner (2016)
Caffeinep.o.First-order input/outputNo exposure dataRamakrishnan et al. (2013)
COPD and asthmaSalmeterolPULFirst-order outputNo exposure dataMusuamba et al. (2015)
Salmeterol, PF-00610355PULEqual input/output rateNo exposure dataNielsen et al. (2012)a
Experimental compoundPULFirst-order input/outputNo exposure dataWu et al. (2011)a
LABA bronchodilatorsPULNo exposure dataAgoram et al. (2008)
Cortisol secretionAdrenocorticotropini.v. infusionSquare wave of inputShow utility of DRTGabrielsson and Peletier (2014)
DiabetesGlucokinase activatorp.o.First-order input/outputNo exposure dataJauslin et al. (2012)
Diabetic macular edemaTriamcinolone acetonideIntravitrealAudren et al. (2004)
GlaucomaPF-04475270TopicalLimited exposureLuu et al. (2009)
Hyper-parathyroidismR-568p.o.First-order input/outputNo exposure dataLalonde et al. (1999)
Hyper-phenylalaninemiaTetrahydrobiopterini.v. infusionFirst-order outputNo exposure dataTrefz et al. (2015)a
HypotensionSodium nitroprussidei.v. infusionFirst-order outputFast SNP exposureBarrett et al. (2015)
Muscle relaxantTubocurarinei.m.First-order outputNo exposure dataLevy, 1964)
Vecuroniumi.v. bolusFirst-order outputNo exposure dataBragg et al. (1994), Fisher and Wright (1997), Warwick et al. (1998)
MydriaticsTridihexethyl chloride tropicamidep.o., topicalNo exposure dataSchoenwald and Smolen (1971), Smolen (1971a, 1976b, 1978), Smolen and Weigand (1973)
Myocardial necrosisInduced by handlingMikaelian et al. (2013)a
ObesityPF-05231023i.v. injectionFirst-order input/outputNo exposure dataThompson et al. (2016)a
OncologyCapecitabinep.o.No exposure dataPaule et al. (2012)a
Capecitabine/docetaxelp.o. (capecitabine), i.v. (docetaxel)No exposure dataFrances et al. (2011)
Carboplatin, pegylated liposomal doxorubicin, paclitaxeli.v. infusionFirst-order outputNo exposure dataWilbaux et al. (2014)a
Carboplatin, cyclophosphamide, thiotepai.v. infusionFirst-order outputNo exposure dataRamon-Lopez et al. (2009) a
Chemotherapy hormonotherapyi.v. infusionFirst-order outputNo exposure dataWilbaux et al. (2015)a
Cisplatin, carboplatin, etoposidei.v. infusionFirst-order outputNo exposure dataBuil-Bruna et al. (2014)a
CyaA-E7i.v. infusionFirst-order outputNo exposure dataParra-Guillen et al. (2013)a
Gemcitabine, carboplatini.v. infusionFirst-order outputNo exposure dataTham et al. (2008)
Irinotecan, MBLI87i.p.First-order outputNo exposure dataSostelly et al. (2014)a
Paclitaxel, nab-paclitaxel, ixabepilonei.v. infusionFirst-order outputNo exposure dataMehrotra et al. (2017)
Temozolomidep.o.First-order outputNo exposure dataMazzocco et al. (2015), Bogdańska et al. (2017)
Oncology and autoimmune diseaseMonoclonal antibodiesi.v. infusion, s.c.First-order input/outputLange and Schmidli (2014, 2015)
Osteoporosis, nutrient supplementationBisphosphonate, denosumabi.v. infusion, p.o.First-order outputNo exposure datavan Schaick et al. (2015)
Ibandronatei.v. infusion, p.o.First-order outputNo exposure dataPillai et al. (2004), Reginster and Gieschke (2006), Zaidi et al. (2006)
Calciump.o.First-order input/outputNo exposure dataAhn et al. (2014)a
PsychomotorPhencyclidine, dextroamphetamines.c.First-order input/outputNo exposure dataJacobs et al. (2010)a
Thermoregulation8-OH-DPATp.o.First-order input/outputNo exposure dataGabrielsson et al. (2000)
ThrombocytopeniaCarboplatin, radiationi.v. infusionNo exposure dataKrzyzanski et al. (2015)
Romiplostims.c.First-order outputNo exposure dataPerez-Ruixo et al. (2012)
Virus infectionHPAI H5N1 virusNo exposure dataKitajima et al. (2011)
  • 8-OH-DPAT, 7-(dipropylamino)-5,6,7,8-tetrahydronaphthalen-1-ol; AChE, acetylcholinesterase; CNS, central nervous system; COPD, chronic obstructive pulmonary disease; EPO, erythropoietin; HPAI, highly pathogenic Asian avian influenza; LABA, long-acting beta agonists; MBLI87, acridone derivative undergoing pre-clinical development; PDN, prednisone; PF-04475270, 5-{3-[(2S)-2-{(3R)-3-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl}-5-oxopyrrolidin-1-yl]propyl}thiophene-2-carboxylate (PF-04475270); PF-05231023, a long-acting FGF21 analog; PF-00610355, beta-adrenoceptor agonist; PUL, pulmonary; R-568, calcimimetic R-568, a type II indirect allosteric CaSR modulator; TC-1734, nicotinic acetylcholine receptor modulator.

  • a Denotes publications referring to the K-PD approach but applying the biophase amount Ab originally proposed by Smolen (1971a).