Pharmacokinetics of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4- nitro-3-trifluoromethyl-phenyl)-propionamide in rats, a non-steroidal selective androgen receptor modulator

J. D. Kearbey, D. Wu, W. Gao, Duane Miller, J. T. Dalton

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

1. S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3- trifluoromethyl-phenyl)-propionamide (also known as S-4) is a non-steroidal selective androgen receptor modulator demonstrating tissue-selective androgenic and anabolic effects. The purpose of the present study was to examine the systemic pharmacokinetics, elimination and oral bioavailability of S-4 in rats. 2. Thirty-five male Sprague-Dawley rats weighing approximately 250 g were randomly assigned to one of seven treatment groups. Intravenous doses of 0.5, 1, 10, and 30 mg kg-1 were given via a jugular catheter. Oral doses of 1, 10 and 30 mg kg-1 were administered via gavage. Plasma concentrations were determined using a validated high-performance liquid chromatography or by a high-performance liquid chromatography/ mass spectrometry method. 3. Clearances ranged between 1.0 and 2.1 ml min-1 kg -1 and varied with dose. The volume of distribution was approximately 0.448 l kg-1 in all treatment groups. Oral bioavailability was also dose dependent, with the lower doses showing complete oral bioavailability. The half-life of S-4 over the dose range tested was between 2.6 and 5.3 h. 4. It was demonstrated that S-4 is rapidly absorbed, slowly cleared, and has a moderate volume of distribution in rats. The pharmacokinetics and oral bioavailability of S-4 indicate that it is an excellent candidate for clinical development.

Original languageEnglish (US)
Pages (from-to)273-280
Number of pages8
JournalXenobiotica
Volume34
Issue number3
DOIs
StatePublished - Mar 1 2004

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Pharmacokinetics
Androgen Receptors
Modulators
Biological Availability
Rats
High performance liquid chromatography
High Pressure Liquid Chromatography
Anabolic Agents
Catheters
Weighing
Mass spectrometry
Sprague Dawley Rats
Half-Life
Mass Spectrometry
Neck
Tissue
Plasmas
(S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide)

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

Cite this

Pharmacokinetics of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4- nitro-3-trifluoromethyl-phenyl)-propionamide in rats, a non-steroidal selective androgen receptor modulator. / Kearbey, J. D.; Wu, D.; Gao, W.; Miller, Duane; Dalton, J. T.

In: Xenobiotica, Vol. 34, No. 3, 01.03.2004, p. 273-280.

Research output: Contribution to journalArticle

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