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Dose-Dependent Intestinal Absorption and Significant Intestinal Excretion (Exsorption) of the β-Blocker Pafenolol in the Rat

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Abstract

The elimination of [3H]pafenolol and metabolites was investigated in fasted and fed rats. Separate groups received intravenous doses (0.3 and 3.0 µmol/kg) and oral doses (1 and 25 µmol/kg). After iv administration of pafenolol, the excretion of unchanged drug into urine and feces was about 50 and 25–30% of the given dose, respectively. The predominating mechanism for the excretion of pafenolol into feces was intestinal excretion (exsorption) directly from blood into gut lumen, since only about 3% of a given iv dose was recovered as pafenolol in the bile. When the oral dose was raised from 1 to 25 µmol/kg, the mean (±SD) bioavailability, calculated from urine data, increased from 14 ± 9 to 30 ± 11% (P < 0.05) in the starved rats and from 14 ± 3 to 16 ± 3% in the fed animals. In parallel, the fraction absorbed from the gut (f a) increased from 19 ± 9 to 31 ± 10% in the starved rats and from 16 ± 4 to 19 ± 5% in the fed animals, respectively. This indicates that the low bioavailability is due primarily to poor intestinal uptake.

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Authors and Affiliations

  1. Department of Biopharmaceutics and Pharmacokinetics, University of Uppsala, BMC, Box 580, S-751 23, Uppsala, Sweden

    Hans Lennernäs

  2. Department of Pharmacokinetics and Drug Metabolism, Cardiovascular Research, Astra Hässle AB, Mölndal, Sweden

    Carl-Gunnar Regårdh

Authors
  1. Hans Lennernäs
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  2. Carl-Gunnar Regårdh
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Lennernäs, H., Regårdh, CG. Dose-Dependent Intestinal Absorption and Significant Intestinal Excretion (Exsorption) of the β-Blocker Pafenolol in the Rat. Pharm Res 10, 727–731 (1993). https://doi.org/10.1023/A:1018916017723

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