Bioavailability and Related Pharmacokinetics in Man of Orally Administered L‐5‐Hydroxytryptophan in Steady State

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Abstract
The bioavailability of orally administered L-5-hydroxytryptophan [5-HTP] in steady state was investigated at 4 increasing multiple dose levels in 5 patients suffering from various myoclonic disorders. An L-aromatic amino acid decarboxylase inhibitor was co-administered in all the experiments. The disposition pharmacokinetics of the amino acid were established in the same patients in preceding i.v. single dose experiments. The finding of a direct proportionality between the size of the oral dose level of L-5-HTP and the corresponding areas under the plasma concentration curves within a dosage interval at steady state strongly indicates dose independent, linear pharmacokinetics of the compound. The systemic availability of L-5-HTP exhibited an interindividual range of 47-84%, with a mean value of 69.2% .+-. 4.7 SEM [standard error of the mean]. The absorption took place at a rather slow rate as judged from times of 1.8-3.3 h elapsing from administration of the compound until occurrence of the maximum measured plasma concentrations. Transitory nausea and vomiting were recognized in few instances during the gradual building up of increasing steady state levels of L-5-HTP in the patients, and the importance of a slow initiation of therapeutical treatment with the amino acid is emphasized.