Oral testosterone in oil: pharmacokinetic effects of 5alpha reduction by finasteride or dutasteride and food intake in men

J Androl. 2006 Jan-Feb;27(1):72-8. doi: 10.2164/jandrol.05058.

Abstract

Oral administration of 400 mg of testosterone (T) in oil, when combined with the 5alpha reductase inhibitor dutasteride (D), elevates serum T in medically castrated men to the normal range. In this study, we sought to determine the impact of 1) finasteride (F) and 2) food intake on the serum T and dihydrotestosterone (DHT) levels observed after the oral administration of T in oil. Therefore, we conducted a pharmacokinetic study of oral T in oil, alone or with D or F, in the fasting and fed states in normal men whose endogenous T production was suppressed by the GnRH antagonist acyline. After acyline administration, 7 healthy men (mean age 31 +/- 8 years) were sequentially administered five 400-mg doses of oral T in sesame oil once daily. The first dose of oral T (T-alone) in oil was given while fasting without F or D. The second (fasting) and third (fed) doses were administered after pretreatment with F (T + F). Four days later, the fourth (fasting) and fifth (fed) doses were administered after pretreatment with D (T + D). Blood samples for measurement of serum T and DHT were obtained before T dosing and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after each administration. In the fasting state, 24-hour area-under-the-curve of serum T after oral T administration was significantly greater with coadministration of either D or F compared with T-alone (126 +/- 36 nmol-h/L [T-alone] vs 287 +/- 98 nmol-h/L [T + F] vs 236 +/- 82 nmol-h/L [T + D]; P < .05 for T + F and T + D vs T-alone). Administration of the T with food nonsignificantly decreased serum T levels compared with fasting administration. The administration of oral T in oil combined with either F or D results in serum T levels adequate to treat men with testicular failure. Additional studies of the combination of oral T in oil with 5alpha-reductase inhibitors as a novel form of oral T therapy are warranted.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 5-alpha Reductase Inhibitors*
  • Administration, Oral
  • Adolescent
  • Adult
  • Area Under Curve
  • Azasteroids / administration & dosage*
  • Diet*
  • Dutasteride
  • Enzyme Inhibitors / administration & dosage*
  • Finasteride / administration & dosage*
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors
  • Humans
  • Male
  • Middle Aged
  • Oils
  • Testosterone / administration & dosage*
  • Testosterone / blood
  • Testosterone / pharmacokinetics

Substances

  • 5-alpha Reductase Inhibitors
  • Azasteroids
  • Enzyme Inhibitors
  • Oils
  • Gonadotropin-Releasing Hormone
  • Testosterone
  • Finasteride
  • Dutasteride