Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Calculation of a First-In-Man Dose of 7-O-Succinyl Macrolactin A Based on Allometric Scaling of Data from Mice, Rats, and Dogs

  • Noh, Keumhan (College of Pharmacy, Yeungnam University) ;
  • Kang, Wonku (College of Pharmacy, Chung-Ang University)
  • Received : 2016.08.24
  • Accepted : 2017.01.09
  • Published : 2017.11.01
Download PDF
⟨ Previous Next ⟩

Abstract

7-O-Succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anti-cancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice. Pharmacokinetic parameters were estimated via both noncompartmental and compartmental analysis, and were correlated with body weight and/or the potential maximum life-span. The clearance and distribution volume of SMA in humans were predicted, and a first-in-man dose proposed. A two-compartment model best described the time courses of SMA plasma concentrations after a saturation elimination process was applied to fit the dataset obtained from rats. Incorporation of the maximum potential life-span during allometric scaling was required to improve the estimation of human clearance. The SMA clearance and the distribution volume in the steady state, in a 70-kg adult male, were estimated to be 30.6 L/h and 19.5 L, respectively. To meet the area under the curve (AUC) required for anti-tumour activity, a dose of 100 mg (~1.5 mg/kg) was finally proposed as the first dose for a 70-kg human. Although toxicological profiles derived from non-clinical studies must be considered before any final decision is made, our work will facilitate clinical studies on SMA.

Keywords

References

  1. Bauer, R. (2011) NONMEM User's guide, introduction to NONMEM 7.2.0. ICON Development Solutions, Maryland.
  2. Bergstrand, M., Hooker, A. C., Wallin, J. E. and Karlsson, M. O. (2011) Prediction-corrected visual predictive checks for diagnosing nonlinear mixed-effects models. AAPS J. 13, 143-151. https://doi.org/10.1208/s12248-011-9255-z
  3. Boxenbaum, H. (1982) Interspecies scaling, allometry, physiological time, and the ground plan of pharmacokinetics. J. Pharmacokinet. Biopharm. 10, 201-227. https://doi.org/10.1007/BF01062336
  4. Boxenbaum, H. (1983) Evolutionary biology, animal behavior, fourth-dimensional space, and the raison d'etre of drug metabolism and pharmacokinetics. Drug Metab. Rev. 14, 1057-1097. https://doi.org/10.3109/03602538308991421
  5. Boxenbaum, H. and Ronfeld, R. (1983) Interspecies pharmacokinetic scaling and the Dedrick plots. Am. J. Physiol. 245, R768-R775.
  6. Brown, R. P., Delp, M. D., Lindstedt, S. L., Rhomberg, L. R. and Beliles, R. P. (1997) Physiological parameter values for physiologically based pharmacokinetic models. Toxicol. Ind. Health 13, 407-484. https://doi.org/10.1177/074823379701300401
  7. Chiou, W.L. (1978) Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for the calculation of the area under the plasma level--time curve. J. Pharmacokinet. Biopharm. 6, 539-546. https://doi.org/10.1007/BF01062108
  8. Cosson, V. F., Fuseau, E., Efthymiopoulos, C. and Bye, A. (1997) Mixed effect modeling of sumatriptan pharmacokinetics during drug development. I: Interspecies allometric scaling. J. Pharmacokinet. Biopharm. 25, 149-167. https://doi.org/10.1023/A:1025728028890
  9. Davies, B. and Morris, T. (1993) Physiological parameters in laboratory animals and humans. Pharm. Res. 10, 1093-1095. https://doi.org/10.1023/A:1018943613122
  10. Dedrick, R., Bischoff, K. B. and Zaharko, D. S. (1970) Interspecies correlation of plasma concentration history of methotrexate (NSC-740). Cancer Chemother. Rep. 54, 95-101.
  11. Food and Drug Administration (2005) Guidance for industry: estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER).
  12. Jung, J. W., Kim, J. M., Kwon, M. H., Kim, D. H. and Kang, H. E. (2014) Pharmacokinetics of macrolactin A and 7-O-succinyl macrolactin A in mice. Xenobiotica 44, 547-554. https://doi.org/10.3109/00498254.2013.861542
  13. Kang, Y., Park, S., Kim, H. Y., Kim, D. H. and Kim, J. A. (2012) Inhibitory effects of macrolactin A and 7-O-succinyl macrolactin A on angiogenesis and cancer cell invasion. In Experimental Biology. San Diego Convent ion Center, San Diego.
  14. Keizer, R. J., Karlsson, M. O. and Hooker, A. (2013) Modeling and simulation workbench for NONMEM: tutorial on pirana, PsN, and Xpose. CPT Pharmacometrics Syst. Pharmacol. 2, e50. https://doi.org/10.1038/psp.2013.24
  15. Kelley, S. K., Harris, L. A., Xie, D., Deforge, L., Totpal, K., Bussiere, J. and Fox, J. A. (2001) Preclinical studies to predict the disposition of Apo2L/tumor necrosis factor-related apoptosis-inducing ligand in humans: characterization of in vivo efficacy, pharmacokinetics, and safety. J. Pharmacol. Exp. Ther. 299, 31-38.
  16. Khor, S. P., McCarthy, K., DuPont, M., Murray, K. and Timony, G. (2000) Pharmacokinetics, pharmacodynamics, allometry, and dose selection of rPSGL-Ig for phase I trial. J. Pharmacol. Exp. Ther. 293, 618-624.
  17. Kim, D. H., Kim, H. K., Kim, K. M., Kim, C. K., Jeong, M. H., Ko, C. Y., Moon, K. H. and Kang, J. S. (2011) Antibacterial activities of macrolactin A and 7-O-succinyl macrolactin A from Bacillus polyfermenticus KJS-2 against vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. Arch. Pharm. Res. 34, 147-152. https://doi.org/10.1007/s12272-011-0117-0
  18. Kim, E. and Kang, W. (2013) Pharmacokinetics of uridine following ocular, oral and intravascular administration in rabbits. Biomol. Ther. (Seoul) 21, 170-172. https://doi.org/10.4062/biomolther.2012.103
  19. Kim, E., Shin, B., Kwon, K. I., Bang, J. S. and Kang, W. (2014) Simultaneous determination of 7-O-succinyl macrolactin A and its active major metabolite, macrolactin A in dog plasma using high-performance liquid chromatography with UV detection. J. Sep. Sci. 37, 2833-2836. https://doi.org/10.1002/jssc.201400438
  20. Kim, J. M., Jung, J. W., Kim, D. H., Kang, J. S., Kim, C. G. and Kang, H. E. (2013) A simple and sensitive HPLC-UV determination of 7-O-succinyl macrolactin A in rat plasma and urine and its application to a pharmacokinetic study. Biomed. Chromatogr. 27, 273-279.
  21. Kim, K. M., Lee, J. Y., Kim, C. K. and Kang, J. S. (2009) Isolation and characterization of susurfactin produced by Bacillus polyfermenticus KJS-2. Arch. Pharm. Res. 32, 711-715. https://doi.org/10.1007/s12272-009-1509-2
  22. Li, J. J. and Corey, E. J. (2013) Drug discovery: practices, processes, and perspectives. Wiley & Sons, Inc.
  23. Lin, Y. S., Nguyen, C., Mendoza, J. L., Escandon, E., Fei, D., Meng, Y. G. and Modi, N. B. (1999) Preclinical pharmacokinetics, interspecies scaling, and tissue distribution of a humanized monoclonal antibody against vascular endothelial growth factor. J. Pharmacol. Exp. Ther. 288, 371-378.
  24. Lindbom, L., Pihlgren, P. and Jonsson, E. N. (2005) PsN-Toolkit--a collection of computer intensive statistical methods for non-linear mixed effect modeling using NONMEM. Comput. Methods Programs Biomed. 79, 241-257. https://doi.org/10.1016/j.cmpb.2005.04.005
  25. Mahmood, I. (2007) Application of allometric principles for the prediction of pharmacokinetics in human and veterinary drug development. Adv. Drug Deliv. Rev. 59, 1177-1192. https://doi.org/10.1016/j.addr.2007.05.015
  26. Mahmood, I. and Balian, J. D.(1996a) Interspecies scaling: predicting clearance of drugs in humans. Three different approaches. Xenobiotica 26, 887-895. https://doi.org/10.3109/00498259609052491
  27. Mahmood, I. and Balian, J. D. (1996b) Interspecies scaling: predicting pharmacokinetic parameters of antiepileptic drugs in humans from animals with special emphasis on clearance. J. Pharm. Sci. 85, 411-414. https://doi.org/10.1021/js950400y
  28. Mordenti, J. (1986) Man versus beast: pharmacokinetic scaling in mammals. J. Pharm. Sci. 75, 1028-1040. https://doi.org/10.1002/jps.2600751104
  29. Noh, K., Kim, D. H., Shin, B. S., Yun, H. Y., Kim, E. and Kang, W. (2014) Simultaneous determination of 7-O-succinyl macrolactin A and its metabolite macrolactin A in rat plasma using liquid chromatography coupled to tandem mass spectrometry. J. Pharm. Biomed. Anal. 98, 85-89. https://doi.org/10.1016/j.jpba.2014.05.009
  30. Noh, K., Nepal, M. R., Jeong, K. S., Kim, S. A., Um, Y. J., Seo, C. S., Kang, M. J., Park, P. -H., Kang, W., Jeong, H. G. and Jeong, T. C. (2015) Effects of baicalin on oral pharmacokinetics of caffeine in rats. Biomol. Ther. (Seoul) 23, 201-206. https://doi.org/10.4062/biomolther.2014.134
  31. Noh, K., Oh, D. G., Nepal, M. R., Jeong, K. S., Choi, Y., kang, M. J., Kang, W., Jeong, H. G. and Jeong, T. C. (2016) Pharmacokinetic interaction of chrysin with caffeine in rats. Biomol. Ther. (Seoul) 24, 446-452. https://doi.org/10.4062/biomolther.2015.197
  32. Obach, R. S., Baxter, J. G., Liston, T. E., Silber, B. M., Jones, B. C. MacIntyre, F., Rance, D. J. and Wastall, P. (1997) The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. J. Pharmacol. Exp. Ther. 283, 46-58.
  33. Park, S., Regmi, S. C., Park, S. Y., Lee, E. K., Chang, J. H., Ku, S. K., Kim, D. H. and Kim, J. A. (2014) Protective effect of 7-O-succinyl macrolactin A against intestinal inflammation is mediated through PI3-kinase/Akt/mTOR and $NF-{\kappa}B$ signaling pathways. Eur. J. Pharmacol. 735, 184-192. https://doi.org/10.1016/j.ejphar.2014.04.024
  34. Parke, J., Holford, N. H. and Charles, B. G. (1999) A procedure for generating bootstrap samples for the validation of nonlinear mixed-effects population models. Comput. Methods Programs Biomed. 59, 19-29. https://doi.org/10.1016/S0169-2607(98)00098-4
  35. Paxton, J. W., Kim, S. N. and Whitfield, L. R. (1990) Pharmacokinetic and toxicity scaling of the antitumor agents amsacrine and CI-921, a new analogue, in mice, rats, rabbits, dogs, and humans. Cancer Res. 50, 2692-2697.
  36. Post, T. M., Freijer, J. I., Ploeger, B. A. and Danhof, M. (2008) Extensions to the visual predictive check to facilitate model performance evaluation. J. Pharmacokinet. Pharmacodyn. 35, 185-202. https://doi.org/10.1007/s10928-007-9081-1
  37. Regmi, S. C., Park, S. Y., Kim, S. J., Banskota, S., Shah, S., Kim, D. H. and Kim, J. A. (2015) The anti-tumor activity of succinyl macrolactin A is mediated through the ${\beta}$-catenin destruction complex via the suppression of tankyrase and PI3K/Akt. PLoS ONE 10, e0141753. https://doi.org/10.1371/journal.pone.0141753

Cited by

  1. Estimation of an Appropriate Human Dose of Boesenbergia pandurata Extracts Based on Allometric Scaling Data of Panduratin A in Mice, Rats, and Dogs vol.23, pp.4, 2020, https://doi.org/10.1089/jmf.2019.4564