Metabolism of an oral tryptophan load. I: Effects of dose and pretreatment with tryptophan

Abstract

1 The metabolism of three oral doses of L-tryptophan (50, 25 and 10 mg/kg) in healthy young males has been investigated. 2 There was a linear relationship between both peak and area under curve of the total plasma tryptophan concentrations whilst the relationship between these parameters and plasma free tryptophan was hyperbolic. 3 Before the tryptophan load about 85% of plasma tryptophan was bound to albumin. As plasma tryptophan concentrations increased there was a hyperbolic increase in free tryptophan. Scatchard analysis revealed 1.4 binding sites/molecule albumin with a dissociation constant (Kd) of 57.9 microM. Following administration of L-tryptophan (50 mg/kg) twice daily for 7 days there was no alteration in the number of binding sites but the dissociation constant (Kd) had decreased to 30.9 microM. 4 L-Tryptophan (50 mg/kg twice daily for 7 days) markedly increased both basal plasma total and free tryptophan. However following a further load the total tryptophan curve was comparable to that seen after acute administration. The plasma free tryptophan curve was lowered relative to that seen after an acute dose. 5 Increasing the tryptophan dose shortened the plasma half-life and decreased the volume of distribution and the rate of clearance. Longer term tryptophan administration had no significant effect on plasma half-life or volume of distribution but did decrease the rate of plasma clearance. 6 The plasma kynurenine concentration increased with increasing tryptophan dose and basal concentrations increased markedly after longer term tryptophan administration. 7 Tryptophan administration either acutely or chronically produced little change in urinary tryptophan or 5-hydroxyindole acetic acid excretion. Urinary kynurenine and indole acetic acid excretion increased with increasing doses of tryptophan. 8 Data are discussed in relation to the administration of L-tryptophan for the treatment of depression.