PULMONARY AND BLOOD ENZYME-KINETICS AS PREDICTORS OF PULMONARY METABOLISM OF ESTERS

被引：5

作者：

DICKINSON, PA ^{[1
]}

TAYLOR, G ^{[1
]}

机构：

[1] UNIV WALES COLL CARDIFF,WELSH SCH PHARM,CARDIFF CF1 3XF,S GLAM,WALES

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 1995年 / 116卷 / 02期

关键词：

ESTER; LUNG; BLOOD; ENZYME KINETICS; 4-BIPHENYLACETIC ACID;

D O I：

10.1016/0378-5173(94)00297-I

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The enzymatic hydrolysis of four aliphatic esters of biphenylacetic acid by rat lung homogenate and blood was investigated. The log V-max/K-m ratios derived in both tissues were parabolically related to lipophilicity, similar trends were also observed for log V-max values against lipophilicity. K-m values could not be related to lipophilicity. The pulmonary and blood intrinsic clearances were linearly related, suggesting blood could be used to predict the pulmonary metabolism of esters. Pulmonary extraction ratios, predicted from the intrinsic clearance using the 'well-stirred' model, were negligible.

引用

页码：231 / 236

页数：6

共 17 条

[1]

ANDERSSON P, 1984, J PHARM PHARMACOL, V36, P763, DOI 10.1111/j.2042-7158.1984.tb04868.x

[2]

BRAZZELL RK, 1982, J PHARM SCICICC, V11, P1274

[3]

CHICCARELLI FS, 1980, ARZNEIMITTEL-FORSCH, V30-1, P728

[4] STRUCTURE METABOLISM RELATIONSHIPS IN THE HYDROLYSIS OF NICOTINATE ESTERS BY RAT-LIVER AND BRAIN SUBCELLULAR-FRACTIONS [J].

DURRER, A ;

WALTHER, B ;

RACCIATTI, A ;

BOSS, G ;

TESTA, B .

PHARMACEUTICAL RESEARCH, 1991, 8 (07) :832-839

[5] STRUCTURE-ACTIVITY CORRELATIONS IN METABOLISM OF DRUGS [J].

HANSCH, C ;

LIEN, EJ ;

HELMER, F .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1968, 128 (02) :319-&

[6]

KAWAGUCHI T, 1985, CHEM PHARM BULL, V33, P301

[7] NATURE AND ROLE OF XENOBIOTIC METABOLIZING ESTERASES IN RAT-LIVER, LUNG, SKIN AND BLOOD [J].

MCCRACKEN, NW ;

BLAIN, PG ;

WILLIAMS, FM .

BIOCHEMICAL PHARMACOLOGY, 1993, 45 (01) :31-36

[8] RELATIONSHIP OF APPARENT SYSTEMIC CLEARANCE TO INDIVIDUAL ORGAN CLEARANCES - EFFECT OF PULMONARY CLEARANCE AND SITE OF DRUG ADMINISTRATION AND MEASUREMENT [J].

MEHVAR, R .

PHARMACEUTICAL RESEARCH, 1991, 8 (03) :306-312

[9]

MISTRY M, 1987, DRUG METAB DISPOS, V15, P710

[10] PRODRUGS AS DRUG DELIVERY SYSTEMS .68. CHEMICAL AND PLASMA-CATALYZED HYDROLYSIS OF VARIOUS ESTERS OF BENZOIC-ACID - A REFERENCE SYSTEM FOR DESIGNING PRODRUG ESTERS OF CARBOXYLIC-ACID AGENTS [J].

NIELSEN, NM ;

BUNDGAARD, H .

INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1987, 39 (1-2) :75-85

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