Related Experiment Videos
Comparative Pharmacokinetics of Trientine Dihydrochloride Capsules: A Randomized, Open-Label, Reference-Controlled,
Christian J Hartmann1, Frank Tacke2, Isabelle Mohr3
1University Clinic Duesseldorf, Institute of Clinical Neuroscience and Medical Psychology, Heinrich-Heine-University Duesseldorf, Moorenstrasse 5, 40225, Duesseldorf, Germany.
Background And Objectives:
Trientine dihydrochloride (TETA-2HCl) is an oral copper chelator used for Wilson disease. Because available formulations differ in marketed strength and may have formulation-specific pharmacokinetic properties, this study compared a 250 mg test capsule and a 300 mg reference capsule administered under fasting conditions.
Methods:
This randomized, open-label, balanced, two-treatment, two-period, two-sequence crossover study enrolled 36 healthy adults. Plasma samples collected over 48 h after single-dose administration were analyzed for parent trientine and N1-acetyltriethylenetetramine using validated liquid chromatography (LC)-tandem mass spectrometry (MS/MS). The primary comparative pharmacokinetic evaluation was based on parent trientine Cmax and AUC0-t at the administered strengths. Dose-normalized and metabolite analyses were supportive.
Results:
Thirty-five participants were included in the pharmacokinetic and statistical analyses. Parent trientine was absorbed more rapidly after the test formulation, with median Tmax values of 1.25 versus 2.25 h. At the administered strengths, test/reference geometric least-squares mean ratios (90% confidence intervals) were 114.96% (104.40-126.60) for Cmax and 109.36% (98.40-121.55) for AUC0-t. Dose-normalized ratios were 137.95% (125.28-151.92) and 131.24% (118.08-145.86), respectively, indicating higher exposure per milligram for the test formulation. Metabolite findings were supportive and did not determine the primary comparative conclusion. No serious adverse events occurred; five mild adverse events were reported during post-study safety assessment.
Conclusions:
At the administered strengths, AUC0-t was similar between the formulations, whereas the upper confidence limit for Cmax slightly exceeded 125.00%. Faster absorption and higher dose-normalized exposure with the test formulation indicate formulation-dependent pharmacokinetic differences and support cautious use of bioequivalence terminology outside the specific regulatory assessment context.