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Abstract

The metabolic disposition of laudanosine in dog, rabbit, and man.

P C Canfell, N Castagnoli, M R Fahey, P J Hennis and R D Miller
Drug Metabolism and Disposition November 1986, 14 (6) 703-708;
P C Canfell
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N Castagnoli
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M R Fahey
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P J Hennis
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R D Miller
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Abstract

This paper summarizes the results of studies of the metabolic fate of laudanosine, a major degradation product of atracurium. Intravenous bolus doses of laudanosine (1-3 mg/kg) were administered to eight dogs and two rabbits anesthetized with halothane, and urine and bile samples were collected for up to 6 hr. Urine samples also were collected from two surgical patients given repetitive doses of atracurium. Metabolites were isolated from all samples using C18-Sep Paks. Treatment of the isolates with beta-glucuronidase followed by purification of the hydrolysate by preparative liquid chromatography provided metabolite fractions which were characterized by analytical liquid chromatography and capillary gas chromatography combined with nitrogen-phosphorus and/or electron ionization-mass spectrometric detection. Reference compounds were employed as chromatographic retention time markers. O-Trimethylsilyl, O-tert-butyldimethylsilyl, and N-trifluoroacetyl derivatives of the metabolites and reference compounds were used for gas chromatographic and mass spectrometric analysis. In all three species, the following metabolites of laudanosine were identified: pseudocodamine (4'-desmethyllaudanosine), pseudolaudanine (6-desmethyllaudanosine), laudanine (3'-desmethyllaudanosine), codamine (7-desmethyllaudanosine), N-norlaudanosine, N-norpseudocodamine, and N-norpseudolaudanine.

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Drug Metabolism and Disposition
Vol. 14, Issue 6
1 Nov 1986
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Abstract

The metabolic disposition of laudanosine in dog, rabbit, and man.

P C Canfell, N Castagnoli, M R Fahey, P J Hennis and R D Miller
Drug Metabolism and Disposition November 1, 1986, 14 (6) 703-708;

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Abstract

The metabolic disposition of laudanosine in dog, rabbit, and man.

P C Canfell, N Castagnoli, M R Fahey, P J Hennis and R D Miller
Drug Metabolism and Disposition November 1, 1986, 14 (6) 703-708;
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