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Abstract

Pharmacokinetic analysis of enterohepatic circulation of buprenorphine and its active metabolite, norbuprenorphine, in rats.

M Ohtani, H Kotaki, K Uchino, Y Sawada and T Iga
Drug Metabolism and Disposition January 1994, 22 (1) 2-7;
M Ohtani
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H Kotaki
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K Uchino
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Y Sawada
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T Iga
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Abstract

The pharmacokinetic characteristics of buprenorphine (BN) and its active metabolite, norbuprenorphine (NBN), was investigated using rats. The elimination half-life (t1/2), total body clearance (CLtot), and steady-state volume of distribution (Vdss) of BN (0.6 mg/kg iv dose) in the intact rat were 2.8 hr, 23.3 ml/min/kg, and 4.2 liters/kg, respectively, and those of NBN (0.6 mg/kg iv dose) were 0.9 hr, 35.0 ml/min/kg, and 2.0 liters/kg. Within 24 hr after administration of BN (0.6 mg/kg dose) to the bile-fistula rat, 74.1% of dose was excreted in the bile as BN glucuronide (BN-Glu) and 18.5% as NBN glucuronide (NBN-Glu), and in urine < 3.2% as BN-Glu. After administration of NBN to the bile-fistula rat, 85.1% and 9.1% of the dose were excreted as NGN-Glu in bile and urine, respectively. The existence of the enterohepatic circulation (EHC) of BN and NBN was confirmed by using paired rats: the donor and recipient rats. Within 24 hr after administration of BN (0.6 mg/kg dose) to the donor rat, 58.8% of the dose was reexcreted as NBN-Glu in bile of the recipient and 25.1% as BN-Glu. Based on the results of in vitro metabolism, it was suggested that this increase in the proportion of NBN-Glu in bile observed after one enterohepatic cycling of BN may be due to the first-pass metabolism in the liver. BN was detected in the plasma of the recipient rat after administration of BN, to the donor rat.(ABSTRACT TRUNCATED AT 250 WORDS)

 

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Drug Metabolism and Disposition
Vol. 22, Issue 1
1 Jan 1994
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Abstract

Pharmacokinetic analysis of enterohepatic circulation of buprenorphine and its active metabolite, norbuprenorphine, in rats.

M Ohtani, H Kotaki, K Uchino, Y Sawada and T Iga
Drug Metabolism and Disposition January 1, 1994, 22 (1) 2-7;

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Abstract

Pharmacokinetic analysis of enterohepatic circulation of buprenorphine and its active metabolite, norbuprenorphine, in rats.

M Ohtani, H Kotaki, K Uchino, Y Sawada and T Iga
Drug Metabolism and Disposition January 1, 1994, 22 (1) 2-7;
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