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Abstract

Disposition and pharmacokinetics of naltrexone after intravenous and oral administration in rhesus monkeys.

R H Reuning, S B Ashcraft, J N Wiley and B E Morrison
Drug Metabolism and Disposition November 1989, 17 (6) 583-589;
R H Reuning
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S B Ashcraft
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J N Wiley
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B E Morrison
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Abstract

The purposes of this investigation were to determine the disposition of naltrexone (NTX) in monkeys and assess the role of first-pass metabolism and enterohepatic cycling in the disposition process. Concentrations of naltrexone and three metabolites were determined in plasma and urine as a function of time after po and iv NTX administration in six monkeys. Urinary recovery of NTX and metabolites 0-48 hr after iv administration (10 mg/kg) totaled 52% of the dose. Recovery in feces was minimal. Total urinary excretion of NTX and metabolites after po administration was 89% of that after iv administration, suggestive of good absorption of NTX from solution. However, the area under the plasma level-time curve for NTX after po administration was only 3.6% of that after iv administration, indicating a very high first-pass effect. The calculated extraction ratio was 0.96-0.99. Analysis of plasma level-time and urinary excretion rate-time data for NTX, conjugated NTX, beta-naltrexol, and conjugated beta-naltrexol after iv administration revealed that 1) the decline of plasma levels or urinary excretion rates with time for the conjugated metabolites was parallel to the decline for the apparent precursor; 2) the decline of plasma levels or urinary excretion rates for beta-naltrexol was slower than for naltrexone; and 3) there is evidence for a pronounced enterohepatic cycling of conjugated NTX and conjugated beta-naltrexol that influences the plasma level-time profile of these conjugates and the unconjugated compounds as well.

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Drug Metabolism and Disposition
Vol. 17, Issue 6
1 Nov 1989
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Abstract

Disposition and pharmacokinetics of naltrexone after intravenous and oral administration in rhesus monkeys.

R H Reuning, S B Ashcraft, J N Wiley and B E Morrison
Drug Metabolism and Disposition November 1, 1989, 17 (6) 583-589;

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Abstract

Disposition and pharmacokinetics of naltrexone after intravenous and oral administration in rhesus monkeys.

R H Reuning, S B Ashcraft, J N Wiley and B E Morrison
Drug Metabolism and Disposition November 1, 1989, 17 (6) 583-589;
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