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Titolo:
Biotransformation of theophylline in cirrhotic rats induced by biliary obstruction
Autore:
Park, EJ; Ko, GN; Kim, JB; Sohn, DH;
Indirizzi:
Wonkwangouthv, Coll Pharm, Med Resources Res Ctr, Iksan 570749, Cheonbuk, S Wonkwang Univ Iksan Cheonbuk South Korea 570749 Iksan 570749, Cheonbuk, S
Titolo Testata:
ARCHIVES OF PHARMACAL RESEARCH
fascicolo: 1, volume: 22, anno: 1999,
pagine: 60 - 67
SICI:
0253-6269(199902)22:1<60:BOTICR>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-LIVER-MICROSOMES; HEPATIC-FIBROSIS; METABOLISM; DISEASE; PHARMACOKINETICS; CLEARANCE; CYTOCHROME-P-450; DISPOSITION; PROPEPTIDE; INDUCTION;
Keywords:
theophylline; pharmacokinetics; biliary obstruction; liver cirrhosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Sohn, DH WonkwangnUniv, Coll Pharm, Med Resources Res Ctr, 344-2 Shinyong Dong, Iksa Wonkwang Univ 344-2 Shinyong Dong Iksan Cheonbuk South Korea 570749
Citazione:
E.J. Park et al., "Biotransformation of theophylline in cirrhotic rats induced by biliary obstruction", ARCH PH RES, 22(1), 1999, pp. 60-67

Abstract

The object of this work was to study the pharmacokinetic differences and the cause of these differences in cirrhotic rats induced by biliary obstruction when aminophylline (8 mg/kg as theophylline, i.v.) was administered. The concentrations of theophylline and its major metabolite (1,3-dimethyluricacid) in plasma were determined by HPLC. In addition, formation of 1,3-dimethyluric acid from theophylline in microsomes and the changes in the activity of drug metabolizing enzymes, which are suggested to be involved in theophylline metabolism, were determined. In cirrhotic rats, the systemic clearance of theophylline was reduced to 30% of the control value while AUC (area under the plasma concentration-time curve) and (t(1/2))(beta) were increased 1.3 fold and 3.5 fold, respectively. The formation of 1,3-dimethyluricacid was decreased to 30% of the control value in microsomes of cirrhotic rat liver. In cirrhotic rat liver, activities of aniline hydroxylase (CYP2E1 related), erythromycin-N-demethylase (CYP3A related), and methoxyresorufin-O-demethylase (CYP1A2 related), which were reported to be related with theophylline metabolism, were decreased to 67%, 53%, and 76% that of normal rat liver, respectively. From the results, it can be concluded that in cirrhotic rats induced by biliary obstruction, the total body clearance of theophylline is markedly reduced and it may be due to decreased activity of drugmetabolizing enzymes in liver.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 05:57:08