Experimental Area | Test Compound | Route | Biophase Parameter | Reason for DRT | Reference |
---|---|---|---|---|---|
AChE inhibition by Sarin | Adenosine A1 agonist | s.c., i.m. | First-order input/output | No exposure data | Bueters et al. (2003) |
Anemia | Induced by ribavirin | p.o. | First-order output | No exposure data | Tod et al. (2005) |
EPO | s.c. | Fast EPO exposure | Uehlinger et al. (1992), Port et al. (1998) | ||
Antiarrhythmics | Amiodarone | i.v. bolus plus infusion | First-order input/output | No exposure data | Salem et al. (2016) |
p.o. | |||||
Anticoagulants | Warfarin | p.o. | First-order input/output | Sparse exposure | Hamberg et al. (2010, 2013), Wright and Duffull (2011) |
p.o. | First-order input/output | No exposure data | Kim et al. (2015), Ooi et al. (2017)a | ||
Antidepressants | Clomipramine, lithium | p.o. | First-order input/output | No exposure data | Gruwez et al. (2007) |
Paroxetine, pindolol | p.o. | First-order output | No exposure data | Gruwez et al. (2005) | |
TC-1734 | s.c. | First-order input/output | Utility of DRT | Gatto et al. (2004) | |
Antilipolytic | NiAc | i.v. infusion | First-order output | Utility of DRT | Isaksson et al. (2009), Gabrielsson and Weiner (2010), Andersson et al. (2016) |
i.v. infusion, p.o. | Michaelis–Menten input (p.o.)/first-order output | Utility of DRT | |||
Antinociceptive | Morphine | i.v. infusion | First-order output | No exposure data | Abou Hammoud et al. (2009)a |
Experimental drug | i.v. infusion, s.c. | First-order input/output, biophase availability | Utility of DRT | Gabrielsson et al. (2000), Gabrielsson and Peletier (2014) | |
Arthritis | Fosdagrocorat, prednisone | p.o. | First-order output | No PDN exposure | Shoji et al. (2017)a |
CNS stimulant | Dexamphetamine | i.p. | Utility of DRT | Gabrielsson and Weiner (2016) | |
Caffeine | p.o. | First-order input/output | No exposure data | Ramakrishnan et al. (2013) | |
COPD and asthma | Salmeterol | PUL | First-order output | No exposure data | Musuamba et al. (2015) |
Salmeterol, PF-00610355 | PUL | Equal input/output rate | No exposure data | Nielsen et al. (2012)a | |
Experimental compound | PUL | First-order input/output | No exposure data | Wu et al. (2011)a | |
LABA bronchodilators | PUL | No exposure data | Agoram et al. (2008) | ||
Cortisol secretion | Adrenocorticotropin | i.v. infusion | Square wave of input | Show utility of DRT | Gabrielsson and Peletier (2014) |
Diabetes | Glucokinase activator | p.o. | First-order input/output | No exposure data | Jauslin et al. (2012) |
Diabetic macular edema | Triamcinolone acetonide | Intravitreal | Audren et al. (2004) | ||
Glaucoma | PF-04475270 | Topical | Limited exposure | Luu et al. (2009) | |
Hyper-parathyroidism | R-568 | p.o. | First-order input/output | No exposure data | Lalonde et al. (1999) |
Hyper-phenylalaninemia | Tetrahydrobiopterin | i.v. infusion | First-order output | No exposure data | Trefz et al. (2015)a |
Hypotension | Sodium nitroprusside | i.v. infusion | First-order output | Fast SNP exposure | Barrett et al. (2015) |
Muscle relaxant | Tubocurarine | i.m. | First-order output | No exposure data | Levy, 1964) |
Vecuronium | i.v. bolus | First-order output | No exposure data | Bragg et al. (1994), Fisher and Wright (1997), Warwick et al. (1998) | |
Mydriatics | Tridihexethyl chloride tropicamide | p.o., topical | No exposure data | Schoenwald and Smolen (1971), Smolen (1971a, 1976b, 1978), Smolen and Weigand (1973) | |
Myocardial necrosis | Induced by handling | Mikaelian et al. (2013)a | |||
Obesity | PF-05231023 | i.v. injection | First-order input/output | No exposure data | Thompson et al. (2016)a |
Oncology | Capecitabine | p.o. | No exposure data | Paule et al. (2012)a | |
Capecitabine/docetaxel | p.o. (capecitabine), i.v. (docetaxel) | No exposure data | Frances et al. (2011) | ||
Carboplatin, pegylated liposomal doxorubicin, paclitaxel | i.v. infusion | First-order output | No exposure data | Wilbaux et al. (2014)a | |
Carboplatin, cyclophosphamide, thiotepa | i.v. infusion | First-order output | No exposure data | Ramon-Lopez et al. (2009) a | |
Chemotherapy hormonotherapy | i.v. infusion | First-order output | No exposure data | Wilbaux et al. (2015)a | |
Cisplatin, carboplatin, etoposide | i.v. infusion | First-order output | No exposure data | Buil-Bruna et al. (2014)a | |
CyaA-E7 | i.v. infusion | First-order output | No exposure data | Parra-Guillen et al. (2013)a | |
Gemcitabine, carboplatin | i.v. infusion | First-order output | No exposure data | Tham et al. (2008) | |
Irinotecan, MBLI87 | i.p. | First-order output | No exposure data | Sostelly et al. (2014)a | |
Paclitaxel, nab-paclitaxel, ixabepilone | i.v. infusion | First-order output | No exposure data | Mehrotra et al. (2017) | |
Temozolomide | p.o. | First-order output | No exposure data | Mazzocco et al. (2015), Bogdańska et al. (2017) | |
Oncology and autoimmune disease | Monoclonal antibodies | i.v. infusion, s.c. | First-order input/output | Lange and Schmidli (2014, 2015) | |
Osteoporosis, nutrient supplementation | Bisphosphonate, denosumab | i.v. infusion, p.o. | First-order output | No exposure data | van Schaick et al. (2015) |
Ibandronate | i.v. infusion, p.o. | First-order output | No exposure data | Pillai et al. (2004), Reginster and Gieschke (2006), Zaidi et al. (2006) | |
Calcium | p.o. | First-order input/output | No exposure data | Ahn et al. (2014)a | |
Psychomotor | Phencyclidine, dextroamphetamine | s.c. | First-order input/output | No exposure data | Jacobs et al. (2010)a |
Thermoregulation | 8-OH-DPAT | p.o. | First-order input/output | No exposure data | Gabrielsson et al. (2000) |
Thrombocytopenia | Carboplatin, radiation | i.v. infusion | No exposure data | Krzyzanski et al. (2015) | |
Romiplostim | s.c. | First-order output | No exposure data | Perez-Ruixo et al. (2012) | |
Virus infection | HPAI H5N1 virus | No exposure data | Kitajima 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).