Human Plasma Concentrations of Tolbutamide and Acetaminophen Extrapolated from in vivo Animal Pharmacokinetics Using in vitro Human Hepatic Clearances and Simple Physiologically Based Pharmacokinetic Modeling for Radio-labeled Microdose Clinical Studies
The aim of the current study was to extrapolate the pharmacokinetics of drug substances orally administered in humans from rat pharmacokinetic data using tolbutamide and acetaminophen as model compounds. Adjusted animal biomonitoring equivalents from rat studies based on reported plasma concentratio...
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| Published in | RADIOISOTOPES Vol. 64; no. 8; pp. 509 - 519 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Japan Radioisotope Association
15.08.2015
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0033-8303 1884-4111 1884-4111 |
| DOI | 10.3769/radioisotopes.64.509 |
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| Abstract | The aim of the current study was to extrapolate the pharmacokinetics of drug substances orally administered in humans from rat pharmacokinetic data using tolbutamide and acetaminophen as model compounds. Adjusted animal biomonitoring equivalents from rat studies based on reported plasma concentrations were scaled to human biomonitoring equivalents using known species allometric scaling factors. In this extrapolation, in vitro metabolic clearance data were obtained using liver preparations. Rates of tolbutamide elimination were roughly similar in rat and human liver microsome experiments, but acetaminophen elimination by rat liver microsomes and cytosolic preparations showed a tendency to be faster than those in humans. Using a simple physiologically based pharmacokinetic(PBPK) model, estimated human plasma concentrations of tolbutamide and acetaminophen were consistent with reported concentrations. Tolbutamide cleared in a roughly similar manner in humans and rats, but medical-dose levels of acetaminophen cleared(dependent on liver metabolism) more slowly from plasma in humans than it did in rats. The data presented here illustrate how pharmacokinetic data in combination with a simple PBPK model can be used to assist evaluations of the pharmacological/toxicological potential of new drug substances and for estimating human radiation exposures from radio‐labeled drugs when planning human studies. |
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| AbstractList | The aim of the current study was to extrapolate the pharmacokinetics of drug substances orally administered in humans from rat pharmacokinetic data using tolbutamide and acetaminophen as model compounds. Adjusted animal biomonitoring equivalents from rat studies based on reported plasma concentrations were scaled to human biomonitoring equivalents using known species allometric scaling factors. In this extrapolation, in vitro metabolic clearance data were obtained using liver preparations. Rates of tolbutamide elimination were roughly similar in rat and human liver microsome experiments, but acetaminophen elimination by rat liver microsomes and cytosolic preparations showed a tendency to be faster than those in humans. Using a simple physiologically based pharmacokinetic(PBPK) model, estimated human plasma concentrations of tolbutamide and acetaminophen were consistent with reported concentrations. Tolbutamide cleared in a roughly similar manner in humans and rats, but medical-dose levels of acetaminophen cleared(dependent on liver metabolism) more slowly from plasma in humans than it did in rats. The data presented here illustrate how pharmacokinetic data in combination with a simple PBPK model can be used to assist evaluations of the pharmacological/toxicological potential of new drug substances and for estimating human radiation exposures from radio‐labeled drugs when planning human studies. |
| Author | NISHIYAMA, Sayako YAMAZAKI, Hiroshi SUGIYAMA, Yuichi KUNIKANE, Eriko MURAYAMA, Norie IKEDA, Toshihiko CHIBA, Koji SHIMIZU, Makiko |
| Author_xml | – sequence: 1 fullname: YAMAZAKI, Hiroshi organization: Association for Promoting Drug Development – sequence: 1 fullname: KUNIKANE, Eriko organization: Showa Pharmaceutical University – sequence: 1 fullname: CHIBA, Koji organization: Yokohama College of Pharmacy – sequence: 1 fullname: NISHIYAMA, Sayako organization: Showa Pharmaceutical University – sequence: 1 fullname: MURAYAMA, Norie organization: Showa Pharmaceutical University – sequence: 1 fullname: IKEDA, Toshihiko organization: Yokohama College of Pharmacy – sequence: 1 fullname: SUGIYAMA, Yuichi organization: RIKEN – sequence: 1 fullname: SHIMIZU, Makiko organization: Showa Pharmaceutical University |
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| CitedBy_id | crossref_primary_10_2131_jts_46_371 crossref_primary_10_1021_acs_chemrestox_0c00009 crossref_primary_10_1080_00498254_2017_1288945 crossref_primary_10_1021_acs_chemrestox_8b00307 crossref_primary_10_1080_00498254_2018_1482576 |
| Cites_doi | 10.1080/004982598239614 10.1002/jps.10005 10.1007/BF02974064 10.1016/j.yrtph.2013.01.008 10.1006/taap.1995.1183 10.1038/clpt.2010.206 10.3390/ijerph7093406 10.1023/A:1015927004752 10.1007/s11095-008-9607-2 10.1002/jps.22646 10.1016/j.yrtph.2014.06.028 10.1016/j.yrtph.2014.08.010 10.1016/j.yrtph.2015.03.010 10.1016/j.yrtph.2010.06.008 10.1016/j.etap.2015.02.011 10.1055/s-2005-864099 10.1093/toxsci/kfn190 10.1080/00498250802668863 |
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Pharmacol., 70, 214-21(2014 11) Takano, R., Murayama, N., Horiuchi, K., Kitajima, M., Kumamoto, M., Shono, F. and Yamazaki, H., Blood concentrations of acrylonitrile in humans after oral administration extrapolated from in vivo rat pharmacokinetics, in vitro human metabolism, and physiologically based pharmacokinetic modeling, Regul. Toxicol. Pharmacol., 58, 252-8(2010 7) Tsukada, A., Suemizu, H., Murayama, N., Takano, R., Shimizu, M., Nakamura, M. and Yamazaki, H., Plasma concentrations of melengestrol acetate in humans extrapolated from the pharmacokinetics established in in vivo experiments with rats and chimeric mice with humanized liver and physiologically based pharmacokinetic modeling, Regul. Toxicol. Pharmacol., 65, 316-24(2013 9) Suemizu, H., Sota, S., Kuronuma, M., Shimizu, M. and Yamazaki, H., Pharmacokinetics and effects on serum cholinesterase activities of organophosphorus pesticides acephate and chlorpyrifos in chimeric mice transplanted with human hepatocytes, Regul. 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P. and Shimada, T., Relationship between CYP2C9 and 2C19 genotypes and tolbutamide methyl hydroxylation and S-mephenytoin 4′-hydroxylation activities in livers of Japanese and Caucasian populations, Pharmacogenetics, 7, 103-13(1997 4) Tozuka, Z., Kusuhara, H., Nozawa, K., Hamabe, Y., Ikushima, I., Ikeda, T. and Sugiyama, Y., Microdose study of 14C-acetaminophen with accelerator mass spectrometry to examine pharmacokinetics of parent drug and metabolites in healthy subjects, Clin. Pharmacol. Ther., 88, 824-30(2010 19) Amidon, G. L., Sinko, P. J. and Fleisher, D., Estimating human oral fraction dose absorbed:a correlation using rat intestinal membrane permeability for passive and carrier-mediated compounds, Pharm. Res., 5, 651-4(1988 3) Ikeda, T., Aoyama, S., Tozuka, Z., Nozawa, K., Hamabe, Y., Matsui, T., Kainuma, M., Hasegawa, S., Maeda, K. and Sugiyama, Y., Microdose pharmacogenetic study of 14C-tolbutamide in healthy subjects with accelerator mass spectrometry to examine the effects of CYP2C9＊3 on its pharmacokinetics and metabolism, Eur. J. Pharm. Sci., 49, 642-8(2013 11 12 13 14 15 16 17 18 19 1 2 3 4 5 6 7 8 9 20 10 21 |
| References_xml | – reference: 21) Yamazaki, H., Mori, Y., Toyoshi, K., Nagai, H., Koda, A. and Konishi, Y., A comparative study of the mutagenic activation of N-nitrosopropylamines by various animal species and man:evidence for a cytochrome P-450 dependent reaction, Jpn. J. Cancer. Res., 77, 107-17(1986) – reference: 14) Emoto, C., Murayama, N., Rostami-Hodjegan, A. and Yamazaki, H., Utilization of estimated physicochemical properties as an integrated part of predicting hepatic clearance in the early drug-discovery stage:Impact of plasma and microsomal binding, Xenobiotica, 39, 227-35(2009) – reference: 12) Yamazaki, H., Horiuchi, K., Takano, R., Nagano, T., Shimizu, M., Kitajima, M., Murayama, N. and Shono, F., Human blood concentrations of cotinine, a biomonitoring marker for tobacco smoke, extrapolated from nicotine metabolism in rats and humans and physiologically based pharmacokinetic modeling, Int. J. Environ. Res. Public Health, 7, 3406-21(2010) – reference: 9) Suemizu, H., Sota, S., Kuronuma, M., Shimizu, M. and Yamazaki, H., Pharmacokinetics and effects on serum cholinesterase activities of organophosphorus pesticides acephate and chlorpyrifos in chimeric mice transplanted with human hepatocytes, Regul. Toxicol. Pharmacol., 70, 468-73(2014) – reference: 15) Poulin, P. and Theil, F. P., Prediction of pharmacokinetics prior to in vivo studies. 1. Mechanism-based prediction of volume of distribution, J. Pharm. Sci., 91, 129-56(2002) – reference: 22) McLanahan, E. D., El-Masri, H. A., Sweeney, L. M., Kopylev, L. Y., Clewell, H. J., Wambaugh, J. F. and Schlosser, P. M., Physiologically based pharmacokinetic model use in risk assessment ― why being published is not enough, Toxicol. Sci., 126, 5-15(2012) – reference: 10) Yamazaki, H., Inoue, K. and Shimada, T, Roles of two allelic variants(Arg144Cys and Ile359Leu) of cytochrome P4502C9 in the oxidation of tolbutamide and warfarin by human liver microsomes, Xenobiotica, 28, 103-15(1998) – reference: 18) Edwards, S. W. and Preston, R. J., Systems biology and mode of action based risk assessment, Toxicol. Sci., 106, 312-8(2008) – reference: 20) Arold, G., Donath, F., Maurer, A., Diefenbach, K., Bauer, S., Henneicke-von Zepelin, H. H., Friede, M. and Roots, I., No relevant interaction with alprazolam, caffeine, tolbutamide, and digoxin by treatment with a low-hyperforin St John’s wort extract, Planta. Med., 71, 331-7(2005) – reference: 23) Miyaguchi, T., Suemizu, H., Shimizu, M., Shida, S., Nishiyama, S., Takano, R., Murayama, N. and Yamazaki, H., Human urine and plasma concentrations of bisphenol A extrapolated from pharmacokinetics established in in vivo experiments with chimeric mice with humanized liver and semi-physiological pharmacokinetic modeling, Regul. Toxicol. Pharmacol., 72, 71-6(2015) – reference: 11) Takano, R., Murayama, N., Horiuchi, K., Kitajima, M., Kumamoto, M., Shono, F. and Yamazaki, H., Blood concentrations of acrylonitrile in humans after oral administration extrapolated from in vivo rat pharmacokinetics, in vitro human metabolism, and physiologically based pharmacokinetic modeling, Regul. Toxicol. Pharmacol., 58, 252-8(2010) – reference: 24) Adachi, K., Suemizu, H., Murayama, N., Shimizu, M. and Yamazaki, H., Human biofluid concentrations of mono(2-ethylhexyl)phthalate extrapolated from pharmacokinetics in chimeric mice with humanized liver administered with di(2-ethylhexyl)phthalate and physiologically based pharmacokinetic modeling, Environ. Toxicol. Pharmacol., 39, 1067-1073(2015) – reference: 17) Gargas, M. L., Andersen, M. E., Teo, S. K. O., Batra, R., Fennell, T. R. and Kedderis, G. L., A physiologically based dosimetry description of acrylonitrile and cyanoethylene oxide in the rat, Toxicol. Appl. Pharmacol., 134, 185-94(1995) – reference: 5) Tozuka, Z., Aoyama, S., Nozawa, K., Akita, S., Oh-Hara, T., Adachi, Y. and Ninomiya, S., Comprehensive quantitative and qualitative liquid chromatography-radioisotope-mass spectrometry analysis for safety testing of tolbutamide metabolites without standard samples, J. Pharm. Sci., 100, 4024-36(2011) – reference: 6) Yamashita, M., Suemizu, H., Murayama, N., Nishiyama, S., Shimizu, M. and Yamazaki, H., Human plasma concentrations of herbicidal carbamate molinate extrapolated from the pharmacokinetics established in in vivo experiments with chimeric mice with humanized liver and physiologically based pharmacokinetic modeling, Regul. Toxicol. Pharmacol., 70, 214-21(2014) – reference: 19) Amidon, G. L., Sinko, P. J. and Fleisher, D., Estimating human oral fraction dose absorbed:a correlation using rat intestinal membrane permeability for passive and carrier-mediated compounds, Pharm. Res., 5, 651-4(1988) – reference: 2) Kirschner, A. S., Ice, R. D. and Beierwaltes, W. H., Radiation dosimetry of 131I-19-iodocholesterol:the pitfalls of using tissue concentration data - reply, J. Nucl. Med., 16, 247-8(1975) – reference: 3) Ikeda, T., Aoyama, S., Tozuka, Z., Nozawa, K., Hamabe, Y., Matsui, T., Kainuma, M., Hasegawa, S., Maeda, K. and Sugiyama, Y., Microdose pharmacogenetic study of 14C-tolbutamide in healthy subjects with accelerator mass spectrometry to examine the effects of CYP2C9＊3 on its pharmacokinetics and metabolism, Eur. J. Pharm. Sci., 49, 642-8(2013) – reference: 7) Tsukada, A., Suemizu, H., Murayama, N., Takano, R., Shimizu, M., Nakamura, M. and Yamazaki, H., Plasma concentrations of melengestrol acetate in humans extrapolated from the pharmacokinetics established in in vivo experiments with rats and chimeric mice with humanized liver and physiologically based pharmacokinetic modeling, Regul. Toxicol. Pharmacol., 65, 316-24(2013) – reference: 4) Tozuka, Z., Kusuhara, H., Nozawa, K., Hamabe, Y., Ikushima, I., Ikeda, T. and Sugiyama, Y., Microdose study of 14C-acetaminophen with accelerator mass spectrometry to examine pharmacokinetics of parent drug and metabolites in healthy subjects, Clin. Pharmacol. Ther., 88, 824-30(2010) – reference: 16) Kato, M., Shitara, Y., Sato, H., Yoshisue, K., Hirano, M., Ikeda, T. and Sugiyama, Y., The quantitative prediction of CYP-mediated drug interaction by physiologically based pharmacokinetic modeling, Pharm. Res., 25, 1891-901(2008) – reference: 8) Inoue, K., Yamazaki, H., Imiya, K., Akasaka, S., Guengerich, F. P. and Shimada, T., Relationship between CYP2C9 and 2C19 genotypes and tolbutamide methyl hydroxylation and S-mephenytoin 4′-hydroxylation activities in livers of Japanese and Caucasian populations, Pharmacogenetics, 7, 103-13(1997) – reference: 13) Shim, C-K. and Suh, M-K., Multiple plasma peaks of acetaminophen and ranitidine after simultaneous oral administration to rats, Arch. Pharm. Res., 15, 246-50(1992) – reference: 1) Stabin, M. G., Steps in Dose Calculations. In:Fundamentals of Nuclear Medicine Dosimetry, (Ed. Stabin MG), pp.77-118, Springer，New York(2008) – ident: 8 doi: 10.1080/004982598239614 – ident: 13 doi: 10.1002/jps.10005 – ident: 11 doi: 10.1007/BF02974064 – ident: 5 doi: 10.1016/j.yrtph.2013.01.008 – ident: 1 – ident: 15 doi: 10.1006/taap.1995.1183 – ident: 2 doi: 10.1038/clpt.2010.206 – ident: 10 doi: 10.3390/ijerph7093406 – ident: 17 doi: 10.1023/A:1015927004752 – ident: 19 – ident: 14 doi: 10.1007/s11095-008-9607-2 – ident: 3 doi: 10.1002/jps.22646 – ident: 4 doi: 10.1016/j.yrtph.2014.06.028 – ident: 7 doi: 10.1016/j.yrtph.2014.08.010 – ident: 20 doi: 10.1016/j.yrtph.2015.03.010 – ident: 9 doi: 10.1016/j.yrtph.2010.06.008 – ident: 21 doi: 10.1016/j.etap.2015.02.011 – ident: 6 – ident: 18 doi: 10.1055/s-2005-864099 – ident: 16 doi: 10.1093/toxsci/kfn190 – ident: 12 doi: 10.1080/00498250802668863 |
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| Title | Human Plasma Concentrations of Tolbutamide and Acetaminophen Extrapolated from in vivo Animal Pharmacokinetics Using in vitro Human Hepatic Clearances and Simple Physiologically Based Pharmacokinetic Modeling for Radio-labeled Microdose Clinical Studies |
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