Impact of Diffusion Parameters on Drug Thresholds in Tissues

Bibliography link: Nartsissov Ya. R., Mashkovtseva E. V., Boronovskiy S. E. Impact of Diffusion Parameters on Drug Thresholds in Tissues. Doctor.Ru. 2017; 8(137): 28–31.
13 October 00:00

Study Objective: Тo determine the common rules of formation of an area in tissues where the drug concentration exceeds the threshold value.

Study Design: Оpen analytical comparative study.

Materials and Methods: Spatiotemporal gradients were modelled for drug concentration near its source (a blood vessel or an injection site). A universal virtual phantom of a local tissue area was used for modelling. The results are presented as the dependence of the diffusion area size with the concentration exceeding the threshold value, on the combination of physical and chemical parameters of the environment and source density.

Study Results: It has been found out that irrespective of the drug class, the diffusing material gradient significantly drops in the vicinity of the source surface provided that the ratio of the diffusion coefficient to the constant of drug absorption by tissue is less than the square of the mean radius of an elementary source. Growth in phantom source density will cause increase in the area with higher drug concentration. At the same time, increase in the threshold value of the drug in the test area is greatly dependant on the constant drug concentration on the source surface.

Conclusion: In order to reach the therapeutic effect of a drug in a local area it is required not only to raise the dose, but also to use chemical compounds with the optimal combination of diffusive properties.

Ya. R. Nartsissov — Scientific and Research Institute of Cytochemistry and Molecular Pharmacology, Moscow. E-mail:

E. V. Mashkovtseva — Scientific and Research Institute of Cytochemistry and Molecular Pharmacology, Moscow. E-mail:

S. E. Boronovskiy — Scientific and Research Institute of Cytochemistry and Molecular Pharmacology, Moscow. E-mail:

13 October 00:00
  1. Remington G., Agid O., Foussias G., Ferguson L., McDonald K., Powell V. Clozapine and therapeutic drug monitoring: is there sufficient evidence for an upper threshold? Psychopharmacology (Berl.). 2013; 225(3): 505–18. DOI: 10.1007/s00213-012-2922-7.
  2. Kuroki T., Tanaka T. Threshold of application of antidepressant drugs for treatment of depressive disorder. Seishin Shinkeigaku Zasshi = Psychiatria et neurologia Japonica. 2015; 117(4): 269–76.
  3. Нарциссов Я. Р., Бороновский С. Е., Машковцева Е. В. Влияние геометрии ветвления сосудов на уровень трофических нарушений при формировании очага ишемии. Доктор.Ру. Неврология и Психиатрия. 2015; 5 (106): 18–20. [Nartsissov Ya.R., Boronovskii S.E., Mashkovtseva E.V. Vliyanie geometrii vetvleniya sosudov na uroven' troficheskikh narushenii pri formirovanii ochaga ishemii. Doctor.Ru. Nevrologiya i Psikhiatriya. 2015; 5(106): 18–20. (in Russian)]
  4. Nartsissov Y.R. Geometries of vasculature bifurcation can affect the level of trophic damage during formation of a brain ischemic lesion. Biochem. Soc. Trans. 2017; 45(5): 1097–103. DOI: 10.1042/BST20160418.
  5. Нарциссов Я. Р., Тюкина Е. С., Бороновский С. Е., Шешегова Е. В. Моделирование пространственно-временных распределений концентраций метаболитов в фантомах биологических объектов на примере пиальных оболочек головного мозга крыс. Биофизика. 2013; 58 (5): 887–96. [Nartsissov Ya.R., Tyukina E.S., Boronovskii S.E., Sheshegova E.V. Modelirovanie prostranstvenno-vremennykh raspredelenii kontsentratsii metabolitov v fantomakh biologicheskikh ob"ektov na primere pial'nykh obolochek golovnogo mozga krys. Biofizika. 2013; 58(5): 887–96. (in Russian)]
  6. Kakuji Tojo, Akiharu Isowaki. Pharmacokinetic model for in vivo/in vitro correlation of intravitreal drug delivery. Adv. Drug Deliv. Rev. 2001; 52(1): 17–24.
  7. Caldés A., Colom H., Armendariz Y., Garrido M.J., Troconiz I.F., Gil-Vernet S. et al. Population pharmacokinetics of ganciclovir after intravenous ganciclovir and oral valganciclovir administration in solid organ transplant patients infected with cytomegalovirus. Antimicrob. Agents Chemother. 2009; 53(11): 4816–24. DOI: 10.1128/AAC.00085-09.
  8. Weinberg B.D., Patel R.B., Exner A.A., Saidel G.M., Gao J. Modeling doxorubicin transport to improve intratumoral drug delivery to RF ablated tumors. J. Control. Release. 2007; 124(1–2): 11–9. DOI: 10.1016/j.jconrel.2007.08.023.
  9. Meulemans A., Paycha F., Hannoun P., Vulpillat M. Measurement and clinical and pharmacokinetic implications of diffusion coefficients of antibiotics in tissues. Antimicrob. Agents Chemother. 1989; 33(8): 1286–90.
  10. Spika J.S., Davis D.J., Martin S.R., Beharry K., Rex J., Aranda J.V. Interaction between chloramphenicol and acetaminophen. Arch. Dis. Child. 1986; 61(11): 1121–4.
  11. Lau A. Pharmacokinetics of metronidazole in hospitalized patients. Int. J. Clin. Pharmacol. Ther. Toxicol. 1986; 24(12): 643–5.
  12. Pruijn F.B., Sturman J.R., Sarath Liyanage H.D., Hicks K.O., Hay M.P., Wilson W.R. Extravascular transport of drugs in tumor tissue: effect of lipophilicity on diffusion of tirapazamine analogues in multicellular layer cultures. J. Med. Chem. 2005; 48(4): 1079–87.
  13. Xiaodong Zhou, Brian W. Pogue, Bin Chen, Tayyaba Hasanb. Analysis of effective molecular diffusion rates for verteporfin in subcutaneous versus orthotopic dunning prostate tumors. Photochem. Photobiol. 2004; 79(4): 323–31.
  14. Houle J.M., Andrew Strong A. Clinical pharmacokinetics of verteporfin. J. Clin. Pharmacol. 2002; 42(5): 547–57.
  15. Siepmann J., Siepmann F. Modeling of diffusion controlled drug delivery. J. Control. Release. 2012; 161(2): 351–62. DOI: 10.1016/j.jconrel.2011.10.006.
  16. Garciá-Suástegui W.A., Ramos-Chávez L.A., Rubio-Osornio M., Calvillo-Velasco M., Atzin-Méndez J.A., Guevara J. et al. The role of CYP2E1 in the drug metabolism or bioactivation in the brain. Oxid. Med. Cell. Longev. 2017; 2017: article ID 4680732, 14 pages. DOI: 10.1155/2017/4680732.
  17. Brown W.A., Rosdolsky M. The clinical discovery of imipramine. Am. J. Psychiatry. 2015; 172(5): 426–9. DOI: 10.1176/appi.ajp.2015.14101336.
Новости мировой медицины! Свежие статьи из журнала! Будьте в курсе!

Похожие статьи

Similar article
19 April 00:00, Interview
Doctor.Ru Pediatrics. Vol. 20, No. 3 (2021)
19 April 00:00, Paediatrics
A.V. Aksenov, E.A. Ivanovskaya
Successful Use of Tocilizumab in a Child with Systemic Juvenile Idiopathic Arthritis
Doctor.Ru Pediatrics. Vol. 20, No. 3 (2021)