Pharmacokinetic-pharmacodynamic correlation and brain penetration of sec-butylpropylacetamide, a new CNS drug possessing unique activity against status epilepticus

Molecular Pharmaceutics

Volumn 13, Issue 7, 2016, Pages 2492-2496

  Mawasi, Hafiz ^a   Bibi, David ^a   Shekh Ahmad, Tawfeeq ^a   Shaul, Chanan ^a,b   Blotnik, Simcha ^b   Bialer, Meir ^a,c  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^b HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^c HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

benzodiazepine resistant status epilepticus; new antiepileptic drugs; pharmacokinetic and pharmacodynamic analysis; various parenteral routes of administration

Indexed keywords

ACETAMIDE DERIVATIVE; SEC BUTYLPROPYLACETAMIDE; UNCLASSIFIED DRUG; VALPROIC ACID DERIVATIVE; AMIDE; ANTICONVULSIVE AGENT; BENZODIAZEPINE DERIVATIVE; CENTRAL NERVOUS SYSTEM AGENTS; SEC-BUTYL-PROPYLACETAMIDE; VALPROIC ACID;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTICONVULSANT ACTIVITY; AREA UNDER THE CURVE RATIO; ARTICLE; BRAIN; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG PENETRATION; EPILEPTIC STATE; INTERMETHOD COMPARISON; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PHARMACODYNAMICS; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; RAT; STEREOISOMERISM; VOLUME OF DISTRIBUTION; ANALOGS AND DERIVATIVES; ANIMAL; DRUG EFFECTS; INTRAPERITONEAL DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; MASS FRAGMENTOGRAPHY; METABOLISM; STATUS EPILEPTICUS;

ADMINISTRATION, INTRAVENOUS; AMIDES; ANIMALS; ANTICONVULSANTS; BENZODIAZEPINES; BRAIN; CENTRAL NERVOUS SYSTEM AGENTS; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; INJECTIONS, INTRAPERITONEAL; RATS; STATUS EPILEPTICUS; VALPROIC ACID;

EID: 84979022657     PISSN: 15438384     EISSN: 15438392     Source Type: Journal    
DOI: 10.1021/acs.molpharmaceut.6b00221     Document Type: Article

References (24)

1. Trinka, E.; Cock, H.; Hesdorffer, D.; Rossetti, A. O.; Scheffer, I. E.; Shinnar, S.; Shorvon, S.; Lowenstein, D. H. A definition and classification of status epilepticus-Report of the ILAE Task Force on Classification of Status Epilepticus Epilepsia 2015, 56, 1515-1523 10.1111/epi.13121
2. Trinka, E.; Höfler, J.; Leitinger, M.; Rohracher, A.; Kalss, G.; Brigo, F. Pharmacologic treatment of status epilepticus Expert Opin. Pharmacother. 2016, 17, 513-534 10.1517/14656566.2016.1127354
3. White, H. S.; Alex, A. B.; Pollock, A. et al. A new derivative of valproic acid amide possesses a broad-spectrum antiseizure profile and unique activity against status epilepticus and organophosphate neuronal damage Epilepsia 2012, 53, 134-146 10.1111/j.1528-1167.2011.03338.x
4. Pouliot, W.; Bialer, M.; Hen, N. et al. A comparative electrographic analysis of the effect of sec-butyl-propylacetamide on pharmacoresistant status epilepticus Neuroscience 2013, 231, 145-156 10.1016/j.neuroscience.2012.11.005
5. Bialer, M.; Yagen, B. Valproic acid-Second generation Neurotherapeutics 2007, 4, 130-137 10.1016/j.nurt.2006.11.007
6. Bialer, M. Chemical properties of antiepileptic drugs (AEDs) Adv. Drug Delivery Rev. 2012, 64, 887-895 10.1016/j.addr.2011.11.006
7. Bialer, M.; White, H. S. Key factors in the discovery and development of new antiepileptic drugs (AEDs) Nat. Rev. Drug Discovery 2010, 9, 68-83 10.1038/nrd2997
8. Bialer, M.; Johannessen, S. I.; Levy, R. H. et al. Progress report on new antiepileptic drugs: A summary of the Eleventh Eilat Conference (EILAT XI) Epilepsy Res. 2013, 103, 2-30 10.1016/j.eplepsyres.2012.10.001
9. Bialer, M.; Johannessen, S. I.; Levy, R. H. et al. Progress report on new antiepileptic drugs: A summary of the Twelfth Eilat Conference (EILAT XII) Epilepsy Res. 2015, 111, 85-141 10.1016/j.eplepsyres.2015.01.001
10. Shekh-Ahmad, T.; Hen, N.; McDonough, J. H. et al. Valnoctamide and sec-Butylpropylacetamide (SPD) for acute seizures and status epilepticus Epilepsia 2013, 54 (Suppl. s6) 99-102 10.1111/epi.12290
11. Hen, N.; Shekh-Ahmad, T.; Yagen, B. et al. Stereoselective Pharmacodynamic and Pharmacokinetic Analysis of sec-Butylpropylacetamide (SPD), a New CNS-Active Derivative of Valproic Acid with Unique Activity against Status Epilepticus J. Med. Chem. 2013, 56, 6467-6477 10.1021/jm4007565
12. Shekh-Ahmad, T.; Hen, N.; Yagen, B. et al. Stereoselective anticonvuslant and pharmacokinetic analysis of valnoctamide, a CNS-active derivative of valproic acid with low teratogenic potential Epilepsia 2014, 55, 353-361 10.1111/epi.12480
13. Shekh-Ahmad, T.; Mawasi, H.; McDonough, J. H. et al. The potential of Valnoctamide and sec-Butylpropylacetamide (SPD) for acute seizures and status epilepticus (SPD) and valnoctamide and their individual stereoisomers in status epilepticus Epilepsy Behav. 2015, 49, 298-302 10.1016/j.yebeh.2015.04.012
14. Bar-Klein, G.; Swissa, E.; Kamintsky, L. et al. sec-Butylpropylacetamide (SPD) and two of its stereoisomers rapidly terminate paraoxon-induced status epilepticus in rats Epilepsia 2014, 55, 1953-1958 10.1111/epi.12838
15. Tjolsen, A.; Berge, O. G.; Hunskaar, J. et al. The formalin test: An evaluation of the method Pain 1992, 51, 5-17 10.1016/0304-3959(92)90003-T
16. Kaufmann, D.; Bates, E. A.; Yagen, B. et al. sec-Butylpropylacetamide (SPD) has antimigraine properties Cephalalgia 2015, 10.1177/0333102415612773
17. Mawasi, H.; Shekh-Ahmad, T.; Finnell, R. H. et al. Pharmacodynamic and pharmacokinetic analysis of CNS-active constitutional isomers of valnoctamide and sec-butylpropylacetamide-amide derivatives of valproic acid Epilepsy Behav. 2015, 46, 72-78 10.1016/j.yebeh.2015.02.040
18. Blotnik, S.; Bergman, F.; Bialer, M. The disposition of valpromide, valproic acid and valnoctamide in brain, liver, plasma and urine of rats Drug Metab. Dispos. 1996, 24, 560-564
19. Blotnik, S.; Bergman, F.; Bialer, M. The disposition of valproyl glycinamide and valproyl glycine in rats Pharm. Res. 1997, 14, 873-878 10.1023/A:1012143631873
20. Blotnik, S.; Bergman, F.; Bialer, M. Disposition of tetramethylcyclopropane analogues of valpromide in the brain, liver, plasma and urine of rats Eur. J. Pharm. Sci. 1998, 6, 93-98 10.1016/S0928-0987(97)00081-X
21. Spampanato, J.; Dudek, E. F. Valnoctamide enhances phasic inhibition: A potential target mechanism for the treatment of benzodiazepine-refractory status epilepticus Epilepsia 2014, 55, e94-e98 10.1111/epi.12702
22. Meador, K. J.; Baker, G. A.; Browning, N. et al. Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs N. Engl. J. Med. 2009, 360, 1597-1605 10.1056/NEJMoa0803531
23. Tomson, T.; Battino, D.; Bonizzoni, E. et al. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry Lancet Neurol. 2011, 10, 609-6017 10.1016/S1474-4422(11)70107-7
24. European Medicines Agency (EMA) website. http://www.ema.europa.eu/ema/index.jsp?curl=pages/news-and-events/news/2014/10/ws-detail-002186.jsp&mid=WC0b01ac058004d5c1 (accessed Nov 21, 2014).