Pharmacokinetic Cross-Over Study of Pharmacy-Compounded Chenodeoxycholic Acid Capsules Compared to Authorized...

Purpose: The Amsterdam UMC pharmacy has been compounding chenodeoxycholic acid (CDCA) capsules for Dutch cerebrotendinous xanthomatosis patients since 2018. However, limited data are available on the pharmacokinetics and bioequivalence of therapeutic CDCA formulations. Methods: An open-label, single-center, randomized, two-period, two-sequence, cross-over study was conducted in 12 healthy volunteers to compare the pharmacokinetic profile of pharmacy-compounded CDCA capsules to that of the authorized CDCA product. Results: Both formulations reached peak plasma concentrations (t_max) at approximately 1 h post-dose. The mean AUC_(0-6h) values were 262.4 (±69.4) µmol∙min/L for the compounded capsules and 248.0 (±78.1) µmol∙min/L for the authorized capsules, with a 90% confidence interval (CI) for the AUC_(0-6h) ratio of 0.89-1.30, exceeding the accepted bioequivalence range of 0.80-1.25. The mean C_max for the compounded formulation (2.96 ± 0.91 µmol/L) was significantly lower than that of the comparator product (4.42 ± 1.36 µmol/L; p = 0.0040), with a 90% CI for the C_max ratio of 0.57-0.80, also outside the bioequivalence range. Conclusions: Overall, the pharmacy-compounded and authorized capsules demonstrate a comparable AUC_(0-6h) and t_max. Bioequivalence could not be demonstrated, primarily due to high variation, a significantly lower C_max, and an AUC_(0-6h) ratio outside the accepted limits. These findings indicate that the compounded formulation results in reduced systemic peak exposure compared with the authorized product. However, given the high variation, a larger sample size would be needed to further investigate bioequivalence in future studies.