Lipophilicities of baclofen ester prodrugs correlate with affinities to the ATP-dependent efflux pump P-glycoprotein: Relevance for their permeation across the blood-brain barrier?

Pharmaceutical Research

Volumn 20, Issue 5, 2003, Pages 772-778

  Leisen, Christiane ^a   Langguth, Peter ^b   Herbert, Bernd ^a   Dressler, Cornelia ^a   Koggel, Annette ^b   Spahn Langguth, Hilde ^a  

^a MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

^b JOHANNES GUTENBERG UNIVERSITY   (Germany)

Author keywords

Baclofen; Octanol water distribution coefficient; P glycoprotein; Prodrug; Radioligand binding assay

Indexed keywords

4 AMINOBUTYRIC ACID DERIVATIVE; ADENOSINE TRIPHOSPHATE; BACLOFEN; BACLOFEN 1 PROPYL ESTER; BACLOFEN 2 PROPYL ESTER; BACLOFEN BUTYL ESTER; BACLOFEN ETHYL ESTER; BACLOFEN METHYL ESTER; ESTER; GLYCOPROTEIN P; OCTANOL; PRODRUG; UNCLASSIFIED DRUG; WATER;

ARTICLE; BINDING AFFINITY; BLOOD BRAIN BARRIER; BRAIN TISSUE; CONCENTRATION RESPONSE; CONTROLLED STUDY; CORRELATION ANALYSIS; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG DISTRIBUTION; DRUG HYDROLYSIS; DRUG PROTEIN BINDING; HUMAN; HUMAN CELL; HYPOTHESIS; IC 50; LIPOPHILICITY; MEMBRANE TRANSPORT; PHYSICAL CHEMISTRY; PRIORITY JOURNAL;

ADENOSINE TRIPHOSPHATE; ANIMALS; BACLOFEN; BLOOD-BRAIN BARRIER; CACO-2 CELLS; ESTERS; HUMANS; MALE; P-GLYCOPROTEIN; PRODRUGS; RATS; RATS, WISTAR;

EID: 0242584997     PISSN: 07248741     EISSN: None     Source Type: Journal    
DOI: 10.1023/A:1023437603555     Document Type: Article

References (24)

1. H. Müller, J. Zierski, D. Dralle, O. Hoffmann, and G. Michaelis. Intrathecal baclofen in spasticity. In: H. Müller, J. Zierski, and R. D. Penn (eds.) Local-Spinal Therapy of Spasticity, Springer Verlag Berlin, Heidelberg, New York, 1988 pp. 155-214.
2. H. Müller, J. Zierski, D. Dralle, D. Krauβ, and E. Mutschler. Pharmacokinetics of intrathecal baclofen. In: H. Müller, J. Zierski, and R. D. Penn (eds.) Local-Spinal Therapy of Spasticity, Springer Verlag Berlin, Heidelberg, New York, 1988 pp. 223-226.
3. Y. Kido, I. Tamai, H. Uchino, F. Suzuki, Y. Sai, and A. Tsuji. Molecular and functional identification of large neutral amino acid transporters LAT1 and LAT2 and their pharmacological relevance at the blood-brain barrier. J. Pharm. Pharmacol. 53:497-503 (2001).
4. H. Matsuo, S. Tsukada, T. Nakata, A. Chairoungdua, D. K. Kim, S. H. Cha, J. Inatomi, H. Yorifuji, J. Fukuda, H. Endou, and Y. Kanai. Expression of a system L neutral amino acid transporter at the blood-brain barrier. NeuroReport 11:3507-3511 (2000).
5. I. Tamai and A. Tsuji. Transporter-mediated permeation of drugs across the blood-brain barrier. J. Pharm. Sci. 89:1371-1388 (2000).
6. I. A. Simpson, N. M. Appel, M. Hokari, J. Oki, G. D. Holman, F. Maher, E. M. Koehler-Stec, S. J. Vannucci, and Q. R. Smith. Blood-brain barrier glucose transporter: effects of hypo- and hyperglycemia revisited. J. Neurochem. 72:238-247 (1999).
7. P. Jolliet-Riant and J. P. Tillement. Drug transfer across the blood-brain barrier and improvement of brain delivery. Fundament. Clin. Pharmacol. 13:16-26 (1999).
8. R. J. Boado, J. Y. Li, M. Nagaya, C. Zhang, and W. M. Pardridge. Selective expression of the large neutral amino acid transporter at the blood-brain barrier. Proc. Natl. Acad. Sci. USA 96:12079-12084 (1999).
9. E. M. Cornford, S. Hyman, and B. E. Swartz. The human brain GLUT1 transporter: ultrastructural localization of the blood-brain barrier endothelia. J. Cereb. Blood Flow Metab. 14:106-112 (1994).
10. M. F. Fromm. P-glycoprotein: a defense mechanism limiting oral bioavailability and CNS accumulation of drugs. Int. J. Clin. Pharmacol. Ther. 38:69-74 (2000).
11. J. Bart, H. J. Groen, N. H. Hendrikse, W. T. van der Graaf, W. Vaalburg, and E. G. de Vries. The blood-brain barrier and oncology: new insights into function and modulation. Cancer Treat. Rev. 26:449-462 (2000).
12. P. L. Golden and W. M. Pardridge. Brain microvascular P-glycoprotein and a revised model of multidrug resistance in brain. Cell. Mol. Neurobiol. 20:165-181 (2000).
13. M. Sugawara, W. Huang, Y. J. Fei, F. H. Leibach, V. Ganapathy, and M. E. Ganapathy. Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2. J. Pharm. Sci. 89:781-789 (2000).
14. R. Niemi, P. Turhanen, J. Vepsalainen, H. Taipale, and T. Jarvinen. Bisphosphonate prodrugs: synthesis and in vitro evaluation of alkyl and acylmethoxy esters of etidronic acid as bioreversible prodrugs of etidronate. Eur. J. Pharm. Sci. 11:173-180 (2000).
15. L. Mizen and G. Burton. The use of esters as prodrugs for oral delivery of beta-lactam antibiotics. Pharm. Biotech. 11:11345-11365 (1998).
16. Y. Deguchi, H. Hayashi, S. Fujii, T. Naito, Y. Yokoyama, S. Yamada, and R. Kimura. Improved brain delivery of a nonsteroidal anti-inflammatory drug with a synthetic glyceride ester: a preliminary attempt at a CNS drug delivery system for the therapy of Alzheimer's disease. J. Drug Target. 8:371-381 (2000).
17. B. Herber. Brain distribution of drugs - Correlation with lipophilicity and dependence on the administration route. PhD thesis, Martin-Luther-University Halle-Wittenberg, Halle/S., Department of Pharmacy (2002)
18. S. Döppenschmitt, H. Spahn-Langguth, C. G. Regardh, and P. Langguth. The role of P-glycoprotein mediated secretion in absorptive drug fluxes. J. Pharm. Sci. 88:1067-1072 (1999).
19. R. C. Baselt, D. Yoshikawa, and J. Chang, and J. Li. Improved long-term stability of blood cocaine in evacuated collection tubes. J. Forensic Sci. 38:935-937 (1993).
20. L. Sachs. Applied Statistics. Springer-Verlag, Berlin, Heidelberg, New York, 1978.
21. M. J. Moll-Navarro, M. Merino, V. G. Casabo, A. Nacher, and A. Polache. Interaction of taurine on baclofen intestinal absorption: a nonlinear mathematical treatment using differential equations to describe kinetic inhibition models. J. Pharm. Sci. 85:1248-1254 (1996).
22. J. B. M. M. van Bree, C. D. Heijligers-Feijen, A. G. de Boer, M. Danhof, and D. D. Breimer. Stereoselective transport of baclofen across the blood-brain barrier in rats as determined by the unit impulse response methodology. Pharm. Res. 8:259-262 (1991).
23. Y. Deguchi, K. Inabe, K. Tomiyasu, K. Nozawa, S. Yamada, and R. Kimura. Study on brain interstitial fluid distribution and blood-brain barrier transport of baclofen in rats by microdialysis. Pharm. Res. 12:1838-1844 (1995).
24. A. Koggel. Influence of secretory transporters on the intestinal permeability of cationic drugs. PhD. thesis, Johannes Gutenberg-University Mainz, Department of Pharmacy (2002).