Preliminary human pharmacokinetics of triletide.

Six healthy volunteers were administered a single 1 g dose of triletide, orally, and blood concentrations of the parent drug determined by high pressure liquid chromatography over a 10-hour period. Analysis of both individual and pooled data indicated that triletide was well absorbed after oral administration, with a lag time of 0.3 hours and the blood peak was reached after about 1.1 to 1.3 hours. Metabolization to desmethyl, desacetyl, desmethyl-desacetyl and hydroxylated derivatives plays a major role in the biotransformation of the drug and thus in its disappearance from blood, the distribution half-life being about 1 hour. Elimination half-life ranged about 5 hours, thus suggesting a dosage schedule of 3-times daily for loading, while for maintenance a twice-daily schedule appears also suitable. The existence of deep compartments and, therefore, risks of accumulation appear to be excluded.