Kinetics and metabolism of 2,2-diethylallylacetamide in dog and man

  • H. Uehleke
  • Maria Brinkschulte-Freitas
Article

Summary

In dogs, slow intravenous injection of 100 mg of diethylallylacetamide (DA) resulted in maximal blood levels of 10–14 μg/ml, and a rapid phase of elimination during 90 min with a half life of 45 min, followed by a slower elimination rate with a half life of 80–90 min.

After oral application of 30 mg DA/kg to female beagle dogs, maximal blood levels of 14 μg/ml were observed after 90–120 min. The blood concentrations declined with a mean half life of 5 h.

In human volunteers, oral doses of 250 mg DA, or rectal application of 300 mg DA produced highest mean blood levels of 4.8 μg/ml (orally), and 5.4 μg/ml (rectally) after 180 min. The mean blood half life was 7.2 h (orally), and 9.2 h (rectal application). Undesirable effects such as nausea, vomiting, and disorientation began to appear at blood levels above 5 μg/ml.

In the urine of dogs and human volunteers, only 2–3% of unchanged DA was recovered, and less than 1% of 2,2-diethyl-4,5-dihydroxypentanoic acid-γ-lactone (DA-lactone) was identified. Acid hydrolysis of the human urine liberated a total of 14–16% of DA-lactone. This percentage was not increased by splitting the urinary conjugates with glucuronidase and glusulase. Small amounts of 2,2-diethylallylacetic acid, 2,2-diethyl-4-one-pentanoic acid, and 2,2-diethyl-4,5-dihydroxypentanamide were detected.

The new metabolites described were synthetized and fully characterized.

Key words

Diethylallylacetamide Pharmacokinetics Diethylallylacetamide metabolites 2,2-Diethyl-4,5-dihydroxypentanoic acid gamma lactone 2,2-Diethylallylacetic acid 

Abbreviations used in the text

AIA

allylisopropylacetamide

DA

2,2-diethylallylacetamide (2,2-diethyl-4-penteneamide)

DA-acid

2,2-diethylallylacetic acid (2,2-diethyl-4-pentenoic acid)

DA-lactone

2,2-diethyl-4,5-dihydroxypentanoic acid-γ-lactone

DA-glycol

2,2-diethyl-4,5-dihydroxypentanamide

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Copyright information

© Springer-Verlag 1978

Authors and Affiliations

  • H. Uehleke
    • 1
  • Maria Brinkschulte-Freitas
    • 1
  1. 1.Pharmakologisches Institut der Universität TübingenTübingenGermany

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