Relative bioavailability of orally dispersible/disintegrating tablet formulations of levo‐ and racemic praziquantel: Two Phase I studies

Abstract

Orally dispersible tablet (ODT) formulations of L‐ and racemic praziquantel (PZQ) are being developed to treat schistosomiasis in preschool‐aged children. Two cross‐over studies (N=32 and 36 resp.) assessed the relative bioavailability of these ODTs versus Cysticide^® in adults.

Bioavailability for L‐PZQ of ODT rac‐PZQ and Cysticide‐^® at 40mg/kg was comparable (L‐PZQ AUC_0‐∞ test/reference ratio [90%CI]: 96% [84%‐111%]), while relative bioavailability of ODT L‐PZQ 20mg/kg was ≈40% that of Cysticide^® 40mg/kg (test/reference: 40% [35%‐46%]). AUC_0∞ and C_max were highly variable in both studies.

For both ODTs, L‐PZQ AUC_0∞ 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 non‐dose‐proportionality of pharmacokinetic 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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