Pharmacokinetics and pharmacodynamics of ritodrine hydrochloride administered orally and intramuscularly to female healthy volunteers

Arzneimittelforschung. 2010;60(8):510-8. doi: 10.1055/s-0031-1296320.

Abstract

Ritodrine hydrochloride ((R,S)-4-hydroxy-alpha-[1-[2-((4-hydroxyphenyl)ethyl]amino)ethyl]benzenemethanol, CAS 26652-09-5) is a direct-acting sympathomimetic agent with a predominant beta-adrenergic activity and a selective action on beta2-receptors. A clinical trial was carried out to investigate the pharmacokinetics, pharmacodynamics and safety of ritodrine hydrochloride administered at the doses of 10, 20 and 30 mg p.o. and 10 mg by i. m. route. A four-way randomised crossover design was adopted on 12 healthy female volunteers with a wash-out of at least 14 days. Concentrations of ritodrine and of the pool of ritodrine in plasma and concentrations of the pool of ritodrine in urine of volunteers were bioassayed with tandem mass spectrometry. The following pharmacokinetic parameters were calculated, using the non-compartmental model: Cmax, AUC0-t, AUC0-INF, t1/2, Vd/f, and Aet after each administration. The distribution volume of ritodrine proved to be about 3 times higher than that of the pool of ritodrine after i. m. injection, confirming the good permeability of ritodrine that massively enters tissue compartments. Statistical analyses of pharmacokinetic parameters ascertained that the p. o. absorption of ritodrine hydrochloride was linearly related with the doses administered in the 10-30 mg range. The pharmacodynamic parameters evaluated complied with the mechanism of action of this drug.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / pharmacokinetics*
  • Adrenergic beta-Agonists / pharmacology*
  • Adult
  • Area Under Curve
  • Blood Pressure / drug effects
  • Cross-Over Studies
  • Female
  • Half-Life
  • Heart Rate / drug effects
  • Humans
  • Injections, Intramuscular
  • Middle Aged
  • Ritodrine / administration & dosage
  • Ritodrine / pharmacokinetics*
  • Ritodrine / pharmacology*
  • Ultrasonography, Doppler, Color
  • Young Adult

Substances

  • Adrenergic beta-Agonists
  • Ritodrine