81
Views
2
CrossRef citations to date
0
Altmetric
Review

The forgotten or underestimated relevance of biopharmaceutical-based assessments for the oral absorption studies of oxime reactivators

, , , , &
Pages 743-752 | Received 07 Mar 2016, Accepted 13 Apr 2016, Published online: 04 May 2016

References

  • Voicu VA, Bajgar J, Medvedovici A, et al. Pharmacokinetics and pharmacodynamics of some oximes and associated therapeutic consequences: a critical review. J Appl Toxicol. 2010;30(8):719–729.
  • Voicu V, Rădulescu FŞ, Medvedovici A. Toxicological considerations of acetylcholinesterase reactivators. Expert Opin Drug Metab Toxicol. 2013;9(1):31–50.
  • Antonijevic B, Stojiljkovic MP. Unequal efficacy of pyridinium oximes in acute organophosphate poisoning. Clin Med Res. 2007;5(1):71–82.
  • Worek F, Wille T, Koller M, et al. Structural requirements for effective oximes-evaluation of kinetic in vitro data with phosphylated human AChE and structurally different oximes. Chem Biol Interact. 2013;203(1):125–128.
  • Voicu V, Rădulescu FŞ, Medvedovici A. Relationships between the antidotal efficacy and structure, PK/PD parameters and bio-relevant molecular descriptors of AChE reactivating oximes: inclusion and integration to biopharmaceutical classification systems. Expert Opin Drug Metab Toxicol. 2015;11(1):95–109.
  • Shih T-M, Kan RK, McDonough JH. In vivo cholinesterase inhibitory specificity of organophosphorus nerve agents. Chem Biol Interact. 2005;157/158:293–303.
  • Skovira JW, O’Donnell JC, Koplovitz I, et al. Reactivation of brain acetylcholinesterase by monoisonitrosoacetone increases the therapeutic efficacy against nerve agents in guinea pigs. Chem Biol Interact. 2010;187(1–3):318–324.
  • Hou T, Wang J. Structure-ADME relationship: still a long way to go? Expert Opin Drug Metab Toxicol. 2008;4(6):759–770.
  • Kennedy T. Managing the drug discovery/development interface. Drug Discov Today. 1997;2(10):436–444.
  • Segall MD, Beresford AP, Gola JM, et al. Focus on success: using a probabilistic approach to achieve an optimal balance of compound properties in drug discovery. Expert Opin Drug Metab Toxicol. 2006;2(2):325–337.
  • Petroianu GA. The history of cholinesterase reactivation: hydroxylamine and pyridinium aldoximes. Pharmazie. 2012;67(10):874–879.
  • Norinder U, Haeberlein M. Computational approaches to the prediction of the blood-brain distribution. Adv Drug Deliv Rev. 2002;54(3):291–313.
  • Pajouhesh H, Lenz GR. Medicinal chemical properties of successful central nervous system drugs. NeuroRx. 2005;2(4):541–553.
  • Seiler P. Interconversion of lipophilicities from hydrocarbon/water systems into n-octanol/water system. Eur J Med Chem. 1974;9:473–479.
  • Lipinski CA, Lombardo F, Dominy BW, et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 1997;23:3–25.
  • Broccatelli F, Larregieu CA, Cruciani G, et al. Improving the prediction of the brain disposition for orally administered drugs using BDDCS. Adv Drug Deliv Rev. 2012;64(1):95–109.
  • Butler JM, Dressman JB. The developability classification system: application of biopharmaceutics concepts to formulation development. J Pharm Sci. 2010;99(12):4940–4954.
  • Kim MK, Shim C-K. The transport of organic cations in the small intestine: current knowledge and emerging concepts. Arch Pharm Res. 2006;29(7):605–616.
  • Veber DF, Johnson SR, Cheng H-Y, et al. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002;45(12):2615–2623.
  • Congreve M, Carr R, Murray C, et al. A ‘rule of three’ for fragment-based lead discovery? Drug Discov Today. 2003;8(19):876–877.
  • Didziapetris R, Japertas P, Avdeef A, et al. Classification analysis of P-glycoprotein substrate specificity. J Drug Target. 2003;11(7):391–406.
  • Gleeson MP. Generation of a set of simple, interpretable ADMET rules of thumb. J Med Chem. 2008;51(4):817–834.
  • Hughes JD, Blagg J, Price DA, et al. Physiochemical drug properties associated with in vivo toxicological outcomes. Bioorg Med Chem Lett. 2008;18(17):4872–4875.
  • Johnson TW, Dress KR, Edwards M. Using the Golden Triangle to optimize clearance and oral absorption. Bioorg Med Chem Lett. 2009;19(19):5560–5564.
  • Doak BC, Over B, Giordanetto F, et al. Oral druggable space beyond the rule of 5: insights from drugs and clinical candidates. Chem Biol. 2014;21(9):1115–1142.
  • Doak BC, Zheng J, Dobritzsch D, et al. How beyond rule of 5 drugs and clinical candidates bind to their targets. J Med Chem. 2016;59(6):2312–2327.
  • Arnott JA, Planey SL. The influence of lipophilicity in drug discovery and design. Expert Opin Drug Discov. 2012;7(10):863–875.
  • Hann MM. Molecular obesity, potency and other addictions in drug discovery. Med Chem Commun. 2011;2:349–355.
  • Voicu VA, de Leon J, Medvedovici AV, et al. New insights on the consequences of biotransformation processes on the distribution and pharmacodynamic profiles of some neuropsychotropic drugs. Eur Neuropsychopharmacol. 2012;22(5):319–329.
  • Clark DE. In silico prediction of blood-brain barrier permeation. Drug Discov Today. 2003;8(20):927–933.
  • Fischer H, Gottschlich R, Seelig A. Blood-brain barrier permeation: molecular parameters governing passive diffusion. J Membr Biol. 1998;165(3):201–211.
  • Ekström F, Pang Y-P, Boman M, et al. Crystal structures of acetylcholinesterase in complex with HI-6, Ortho-7 and obidoxime: structural basis for differences in the ability to reactivate tabun conjugates. Biochem Pharmacol. 2006;72(5):597–607.
  • Okuno S, Sakurada K, Ohta H, et al. Blood-brain barrier penetration of novel pyridinealdoxime methiodide (PAM)-type oximes examined by brain microdialysis with LC-MS/MS. Toxicol Appl Pharmacol. 2008;227(1):8–15.
  • Lobell M, Molnár L, Keserü GM. Recent advances in the prediction of blood-brain partitioning from molecular structure. J Pharm Sci. 2003;92(2):360–370.
  • Hann MM, Keserü GM. Finding the sweet spot: the role of nature and nurture in medicinal chemistry. Nat Rev Drug Discov. 2012;11(5):355–365.
  • Musil K, Florianova V, Bucek P, et al. Development and validation of a FIA/UV-vis method for pK(a) determination of oxime based acetylcholinesterase reactivators. J Pharm Biomed Anal. 2016;117:240–246.
  • Lundy PM, Shih TM. Examination of the role of central cholinergic mechanisms in the therapeutic effects of HI-6 in organophosphate poisoning. J Neurochem. 1983;40(5):1321–1328.
  • Kassa J, Bajgar J. Changes of acetylcholinesterase activity in various parts of brain following nontreated and treated soman poisoning in rats. Mol Chem Neuropathol. 1998;33(3):175–184.
  • Lorke DE, Kalasz H, Petroianu GA, et al. Entry of oximes into the brain: a review. Curr Med Chem. 2008;15(8):743–753.
  • Shih T-M, Skovira JW, O’Donnell JC, et al. Treatment with tertiary oximes prevents seizures and improves survival following sarin intoxication. J Mol Neurosci. 2010;40(1–2):63–69.
  • Shek E, Higuchi T, Bodor N. Improved delivery through biological membranes. 2. Distribution, excretion, and metabolism of N-methyl-1,6-dihydropyridine-2-carbaldoxime hydrochloride, a pro-drug of N-methylpyridinium-2-carbaldoxime chloride. J Med Chem. 1976;19(1):108–112.
  • Shek E, Higuchi T, Bodor N. Improved delivery through biological membranes. 3. Delivery of N-methylpyridinium-2-carbaldoxime chloride through the blood-brain barrier in its dihydropyridine pro-drug form. J Med Chem. 1976;19(1):113–117.
  • Rump S, Faff J, Borkowska G, et al. Central therapeutic effects of dihydroderivative of pralidoxime (pro-2-PAM) in organophosphate intoxication. Arch Int Pharmacodyn Ther. 1978;232(2):321–332.
  • Shih T-M, Guarisco JA, Myers TM, et al. The oxime pro-2-PAM provides minimal protection against the CNS effects of the nerve agents sarin, cyclosarin, and VX in guinea pigs. Toxicol Mech Methods. 2011;21(1):53–62.
  • Shih TM, Koplovitz I, Kan RK, et al. In search of an effective in vivo reactivator for organophosphorus nerve agent-inhibited acetylcholinesterase in the central nervous system. Adv Stud Biol. 2012;4:451–478.
  • Askew BM. Oximes and hydroxamic acids as antidotes in anticholinesterase poisoning. Br J Pharmacol Chemother. 1956;11(4):417–423.
  • Kerns EH, Di L, Carter GT. In vitro solubility assays in drug discovery. Curr Drug Metab. 2008;9(9):879–885.
  • Lorke DE, Petroianu GA. Minireview: does in-vitro testing of oximes help predict their in-vivo action after paraoxon exposure? J Appl Toxicol. 2009;29(6):459–469.
  • Wager TT, Hou X, Verhoest PR, et al. Moving beyond rules: the development of a central nervous system multiparameter optimization (CNS MPO) approach to enable alignment of druglike properties. ACS Chem Neurosci. 2010;1(6):435–449.
  • Korabecny J, Soukup O, Dolezal R, et al. From pyridinium-based to centrally active acetylcholinesterase reactivators. Mini Rev Med Chem. 2014;14(3):215–221.
  • Renou J, Mercey G, Verdelet T, et al. Syntheses and in vitro evaluations of uncharged reactivators for human acetylcholinesterase inhibited by organophosphorus nerve agents. Chem Biol Interact. 2013;203(1):81–84.
  • Wei Z, Liu Y-Q, Zhou X-B, et al. New efficient imidazolium aldoxime reactivators for nerve agent-inhibited acetylcholinesterase. Bioorg Med Chem Lett. 2014;24(24):5743–5748.
  • Kalisiak J, Ralph EC, Cashman JR. Nonquaternary reactivators for organophosphate-inhibited cholinesterases. J Med Chem. 2012;55(1):465–474.
  • Katz FS, Pecic S, Tran TH, et al. Discovery of new classes of compounds that reactivate acetylcholinesterase inhibited by organophosphates. Chembiochem. 2015;16(15):2205–2215.
  • Sakurada K, Matsubara K, Shimizu K, et al. Pralidoxime iodide (2-PAM) penetrates across the blood-brain barrier. Neurochem Res. 2003;28(9):1401–1407.
  • Koepsell H. Role of organic cation transporters in drug-drug interaction. Expert Opin Drug Metab Toxicol. 2015;11(10):1619–1633.
  • Joosen MJ, van der Schans MJ, van Dijk CG, et al. Increasing oxime efficacy by blood-brain barrier modulation. Toxicol Lett. 2011;206(1):67–71.
  • Ligtenstein DA, Kossen SP. Kinetic profile in blood and brain of the cholinesterase reactivating oxime HI-6 after intravenous administration to the rat. Toxicol Appl Pharmacol. 1983;71(2):177–183.
  • Mahar Doan KM, Humphreys JE, Webster LO, et al. Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002;303(3):1029–1037.
  • Zvirblis P, Kondritzer AA. Prophylaxis against sarin poisoning in the rat by oral administration of pralidoxime chloride. J Pharmacol Exp Ther. 1967;157(2):432–434.
  • Quinby GE. Feasibility of prophylaxis by oral pralidoxime. Cholinesterase inactivation by organophosphorus pesticides. Arch Environ Health. 1968;16(6):812–820.
  • Holland P, Parkes DC. Plasma concentrations of the oxime pralidoxime mesylate (P2S) after repeated oral and intramuscular administration. Br J Ind Med. 1976;33(1):43–46.
  • Sidell FR, Groff WA. Toxogonin: oral administration to man. J Pharm Sci. 1971;60(6):860–863.
  • Amidon GL, Lennernäs H, Shah VP, et al. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12(3):413–420.
  • Guidance for industry. Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a Biopharmaceutics Classification System. Bethesda (MD): U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER); Aug 2000.
  • Guidance for industry. Draft guidance, revision 1. Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a Biopharmaceutics Classification System. Bethesda (MD): U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER); May 2015.
  • Benet LZ, Broccatelli F, Oprea TI. BDDCS applied to over 900 drugs. AAPS J. 2011;13(4):519–547.
  • Benet LZ, Larregieu CA. The FDA should eliminate the ambiguities in the current BCS biowaiver guidance and make public the drugs for which BCS biowaivers have been granted. Clin Pharmacol Ther. 2010;88(3):405–407.
  • Wu C-Y, Benet LZ. Predicting drug disposition via application of BCS: transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res. 2005;22(1):11–23.
  • Bevan M. Report on proposal for the inclusion of pralidoxime in the WHO model list of essential medicines. 17th Expert Committee on the Selection and Use of Essential Medicines; 2009 Mar; Geneva.
  • Baggot JD, Buckpitt A, Johnson D, et al. Bioavailability and disposition kinetics of HI-6 in Beagle dogs. Biopharm Drug Dispos. 1993;14(2):93–105.
  • Lemanowicz EF, Sugita ET, Niebergall PJ, et al. Kinetics of absorption and elimination of pralidoxime chloride in dogs. J Pharm Sci. 1979;68(2):141–145.
  • Crook JW, Goodman AI, Colbourn JL, et al. Adjunctive value of oral prophylaxis with the oximes 2-PAM lactate and 2-PAM methanesulfonate to therapeutic administration of atropine in dogs poisoned by inhaled Sarin vapor. J Pharmacol Exp Ther. 1962;136:397–399.
  • Jovanovic D, Maksimovic M, Joksovic D, et al. Oral forms of the oxime HI-6: a study of pharmacokinetics and tolerance after administration to healthy volunteers. Vet Hum Toxicol. 1990;32(5):419–421.
  • Maksimović M, Jovanović D, Kovacević V, et al. Oral kinetics and bioavailability of the cholinesterase reactivator HI-6 after administration of 2 different formulations of tablets to dogs. Toxicol Lett. 1987;39(1):85–91.
  • Kondritzer AA, Zvirblis P, Goodman A, et al. Blood plasma levels and elimination of salts of 2-PAM in man after oral administration. J Pharm Sci. 1968;57(7):1142–1146.
  • Sidell FR, Groff WA, Ellin RI. Blood levels of oxime and symptoms in humans after single and multiple oral doses of 2-pyridine aldoxime methochloride. J Pharm Sci. 1969;58(9):1093–1098.
  • Kuneš M, Květina J, Bureš J, et al. HI-6 oxime (an acetylcholinesterase reactivator): blood plasma pharmacokinetics and organ distribution in experimental pigs. Neuro Endocrinol Lett. 2014;35(S2):191–196.
  • Gibbon SL, Tong H, Miranda PMS, et al. Metabolism of pralidoxime (2-PAM) in man. J Anal Toxicol. 1979;3(1):14–17.
  • Enander I, Sundwall A, Sorbo B. Metabolic studies on N-methylpyridinium-2-aldoxime. I. The conversion to thiocyanate. Biochem Pharmacol. 1961;7:226–231.
  • Garrigue H, Maurizis JC, Madelmont JC, et al. Disposition and metabolism of acetylcholinesterase reactivators 2PAM-I, TMB4 and R665 in rats submitted to organophosphate poisoning. Xenobiotica. 1991;21(5):583–595.
  • Garrigue H, Maurizis JC, Nicolas C, et al. Disposition and metabolism of two acetylcholinesterase reactivators, pyrimidoxime and HI6, in rats submitted to organophosphate poisoning. Xenobiotica. 1990;20(7):699–709.
  • Brown ND, Gray RR, Stermer-Cox MG, et al. Stability study of HI-6 dichloride in various anticholinergic formulations. J Chromatogr. 1984;315:389–394.
  • Khan FA, Campbell AJ, Hoyt B, et al. Oxidative mechanisms for the biotransformation of 1-methyl-1,6-dihydropyridine-2-carbaldoxime to pralidoxime chloride. Life Sci. 2011;89(25–26):911–917.
  • Bajgar J, Fusek J, Kassa J, et al. An attempt to assess functionally minimal acetylcholinesterase activity necessary for survival of rats intoxicated with nerve agents. Chem Biol Interact. 2008;175(1–3):281–285.
  • Petroianu GA, Athauda G, Darvas F, et al. K-oxime (K-27): phosphylation-induced changes in logP. Mil Med Sci Lett. 2014;83:1–7.
  • Petroianu GA, Lorke DE, Athauda G, et al. Pralidoxime and obidoxime: phosphylation induced changes in logP (partition coefficient). J Environ Immunol Toxicol. 2013;1(1):35–40.
  • Luo C, Saxena A, Smith M, et al. Phosphoryl oxime inhibition of acetylcholinesterase during oxime reactivation is prevented by edrophonium. Biochemistry. 1999;38(31):9937–9947.
  • Ashani Y, Bhattacharjee AK, Leader H, et al. Inhibition of cholinesterases with cationic phosphonyl oximes highlights distinctive properties of the charged pyridine groups of quaternary oxime reactivators. Biochem Pharmacol. 2003;66(2):191–202.
  • Kloog Y, Galron R, Balderman D, et al. Reversible and irreversible inhibition of rat brain muscarinic receptors is related to different substitutions on bisquaternary pyridinium oximes. Arch Toxicol. 1985;58(1):37–39.
  • Soukup O, Tobin G, Kumar UK, et al. Characterization of the anticholinergic properties of obidoxime; functional examinations of the rat atria and the urinary bladder. Toxicol Mech Methods. 2010;20(7):428–433.
  • Soukup O, Krůšek J, Kaniaková M, et al. Oxime reactivators and their in vivo and in vitro effects on nicotinic receptors. Physiol Res. 2011;60(4):679–686.
  • Ring A, Strom BO, Turner SR, et al. Bispyridinium compounds inhibit both muscle and neuronal nicotinic acetylcholine receptors in human cell lines. PLoS One. 2015;10(8):e0135811.
  • Soukup O, Kumar UK, Proska J, et al. The effect of oxime reactivators on muscarinic receptors: functional and binding examinations. Environ Toxicol Pharmacol. 2011;31(3):364–370.
  • Voicu VA, Miu C, Jiquidi M, et al. Medicine for control and treatment of toxic effects of organic–phosphoric compounds. RO Patent 79914. 1974.
  • Levine RR, Steinberg GM. Intestinal absorption of pralidoxime and other aldoximes. Nature. 1966;209(5020):269–271.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.