[Pharmacokinetics and metabolite pattern of clenbuterol in the rat]

Arzneimittelforschung. 1976;26(7a):1435-41.
[Article in German]

Abstract

Pharmacokinetics and metabolite pattern of the beta-sympathomimetic 4-amino-alpha-[tert.-butylamino)methyl]-3,5-dichlorobenzyl alcohol hydrochloride (clenbuterol, NAB 365) have been investigated in the rat. After a single i.v. dose of 2 mg/kg 14C-NAB 365 up to 10 min p.a. the blood level falls very steeply and 15 min p.a. there is an increase to be observed. A maximum blood level of 0.85 mug eq. NAB 365/ml is achieved. Then a biphasic elimination of radioactivity from the blood occurs. After a single oral dose of 2 mg/kg the maximum blood level of 0.5 mug/ml is attained 2 h p.a. Again a biphasic elimination occurs. 26 h is the half-life of the slower of two elimination processes for i.v. and p.o. administration, respectively. Elimination predominantly takes place via the kidneys. After i.v. administration 85% and after p.o. administration 80% of the radioactivity applied are eliminated in urine and faeces. The main portion of radioactivity had been eliminated by 48 h p.a. As can be seen from the urinary radioactivity absorption is complete. Following i.v. dosing the excretion is slightly faster than after p.o. administration. Whole-body autoradiography and the distribution of radioactivity in the organs show a relatively slow absorption after p.o. dosing. In the pregnant mouse the placenta barrier is passed but the fetuses contain far less radioactivity than the mother animal. Clenbuterol is metabolized in the rat. 70% of the radioactivity represents the unchanged parent compound in urine (38% of the administered radioactivity). 8 metabolites have been established in urine (extracts). Faeces radioactivity mainly contains unchanged clenbuterol and only traces of metabolites. The metabolite pattern of the maximum plasma level (2 h after p.o. administration) and the metabolite pattern of the collected urines are identical. 38% of the administered radioactivity represent unchanged NAB 365 in the urine, whereas there are 45% in the plasma.

Publication types

  • English Abstract

MeSH terms

  • Administration, Oral
  • Animals
  • Autoradiography
  • Biotransformation
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / metabolism*
  • Butylamines / administration & dosage
  • Butylamines / metabolism*
  • Female
  • Injections, Intravenous
  • Kinetics
  • Male
  • Maternal-Fetal Exchange
  • Mice
  • Pregnancy
  • Rats

Substances

  • Bronchodilator Agents
  • Butylamines