Oxazepam esters. 2. Correlation of hydrophobicity with serum binding, brain penetration, and excretion

G. Maksay, Zsuzsanna Tegyey, László Ötvös

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Pharmacokinetics of a series of prodrug-type oxazepam esters were studied in mice. The effect of hydrophobicity was investigated in relation to serum binding, brain penetration, tissue storage, and excretion. Binding to mouse serum and to human serum albumin was measured by equilibrium dialysis, and the changes in binding free energy were correlated with RM values. Brain-blood partition of the esters did not change parallel with their serum binding. An indirect correlation exists between RM of the esters and oxazepam brain accrual. Brain-blood concentration ratios of oxazepam prove that hydrolysis precedes brain penetration and hydrophobicity might primarily influence the hydrolysis rate. The amount of tissue storage and total excretion rates also correlate with hydrophobicity.

Original languageEnglish
Pages (from-to)1443-1447
Number of pages5
JournalJournal of Medicinal Chemistry
Volume22
Issue number12
Publication statusPublished - 1979

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Oxazepam
Hydrophobicity
Hydrophobic and Hydrophilic Interactions
Brain
Esters
Serum
Hydrolysis
Blood
Tissue
Pharmacokinetics
Dialysis
Prodrugs
Serum Albumin
Free energy

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Oxazepam esters. 2. Correlation of hydrophobicity with serum binding, brain penetration, and excretion. / Maksay, G.; Tegyey, Zsuzsanna; Ötvös, László.

In: Journal of Medicinal Chemistry, Vol. 22, No. 12, 1979, p. 1443-1447.

Research output: Contribution to journalArticle

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