Relative Bioavailability of Orally Dispersible Tablet Formulations of Levo‐ and Racemic Praziquantel: Two Phase I Studies

Autor: Wilhelmina Maria Bagchus, Deon Bezuidenhout, Eleanor Harrison‐Moench, Elly Kourany‐Lefoll, Peter Wolna, Oezkan Yalkinoglu
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Clinical and Translational Science, Vol 12, Iss 1, Pp 66-76 (2019)
Druh dokumentu: article
ISSN: 1752-8062
1752-8054
DOI: 10.1111/cts.12601
Popis: Orally dispersible tablet (ODT) formulations of levo praziquantel (L‐PZQ) and racemic PZQ (rac‐PZQ) are being developed to treat schistosomiasis in preschool‐aged children. Two crossover studies (N = 32 and 36, respectively) assessed the relative bioavailability of these ODTs vs. Cysticide in adults. Bioavailability for L‐PZQ of ODT rac‐PZQ and Cysticide at 40 mg/kg was comparable (L‐PZQ area under the concentration‐time curve from zero to infinity (AUC0–∞) test/reference ratio (90% confidence interval (CI)): 96% (84–111%)), whereas relative bioavailability of ODT L‐PZQ 20 mg/kg was ~40% that of Cysticide 40 mg/kg (test/reference: 40% (35–46%)). AUC0‐∞ and peak plasma concentration (Cmax) were highly variable in both studies. For both ODTs, L‐PZQ AUC0–∞ showed greater than dose‐proportional increase over the ranges tested and a significant food effect. Safety was comparable among formulations. The lower bioavailability of ODT L‐PZQ, as well as the high variability and nondose‐proportionality of pharmacokinetic (PK) parameters, highlighted the need for a dedicated pediatric dose‐finding study for the selection of the most appropriate formulation and dose (L‐PZQ ODT or rac‐PZQ ODT).
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