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Abstract

Hepatic and extrahepatic metabolism of salbutamol in anesthetized rabbits.

S Perreault, L Dumont, V Villiere, H Ong, A Adam and P du Souich
Drug Metabolism and Disposition May 1993, 21 (3) 485-491;
S Perreault
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L Dumont
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V Villiere
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H Ong
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A Adam
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P du Souich
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Abstract

Orally administered salbutamol undergoes an extensive first-pass effect. This study investigated the roles of the intestine (INT), liver (HEP), and lung (LUN) in salbutamol extraction. Salbutamol was administered to five groups of anesthetized rabbits by the following routes: intraduodenal (ID) (800 micrograms/kg), intraportal (IP), (60 micrograms/kg), intrajugular (IV) (60 micrograms/kg), endotracheal (ET) (60 micrograms/kg), and intraarterial (IA) (60 micrograms/kg). Multiple blood samples were drawn and the areas under salbutamol plasma concentrations-time curves (AUCs) were calculated. Since IA salbutamol administration generated 100% bioavailability (F), AUCIA was used as a reference for comparison. Salbutamol F values for the ID, IP, IV, and ET routes were 0.013, 0.15, 0.53, and 0.53, respectively. The ratio of the AUC of salbutamol administered before the organ (ID, IP, IV, or ET) to the AUC estimated when given after the organ (IP, IV, and IA) allowed assessment of the extraction ratio (E) of INT, HEP, and LUN, respectively. EINT was 0.92, EHEP was 0.71, and ELUN was 0.47. The mean ratio of the AUC of the metabolite (AUCM) over the AUC of the parent compound was 704 +/- 77 for the ID, compared with 83 +/- 12 for the IP, 11 +/- 1 for the IV, 1.7 +/- 0.3 for the ET routes, and 4 +/- 1 for the IA routes. On the other hand, when the AUCM was normalized by the dose, this ratio was INT = HEP > LUN, suggesting that the ability of INT to conjugate salbutamol is not very important.(ABSTRACT TRUNCATED AT 250 WORDS)

 

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Drug Metabolism and Disposition
Vol. 21, Issue 3
1 May 1993
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Abstract

Hepatic and extrahepatic metabolism of salbutamol in anesthetized rabbits.

S Perreault, L Dumont, V Villiere, H Ong, A Adam and P du Souich
Drug Metabolism and Disposition May 1, 1993, 21 (3) 485-491;

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Abstract

Hepatic and extrahepatic metabolism of salbutamol in anesthetized rabbits.

S Perreault, L Dumont, V Villiere, H Ong, A Adam and P du Souich
Drug Metabolism and Disposition May 1, 1993, 21 (3) 485-491;
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