Dataset Information

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

ABSTRACT: 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).

SUBMITTER: Bagchus WM

PROVIDER: S-EPMC6342245 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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

Bagchus Wilhelmina Maria WM Bezuidenhout Deon D Harrison-Moench Eleanor E Kourany-Lefoll Elly E Wolna Peter P Yalkinoglu Oezkan O

Clinical and translational science 20181221 1

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 (AUC<sub>0-∞</sub> ) test/reference ratio (90% ...[more]

PMID: 30536632

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Project description:Background and objectiveVenetoclax is an approved BCL-2 inhibitor, currently under evaluation in different hematological malignancies in adult and pediatric populations. Venetoclax is available as 10, 50, and 100 mg tablets. To provide an alternative to patients who find taking the commonly prescribed 100 mg tablet a challenge, the interchangeability of lower-strength tablets with the 100 mg tablet was investigated. Additionally, newly developed oral suspension powder formulations to facilitate dosing in pediatrics were evaluated.MethodsPharmacokinetic data from 80 healthy female participants from three phase I studies were utilized to evaluate the bioavailability of (1) 10 and 50 mg tablets relative to a 100 mg tablet; (2) 0.72 and 7.2% (drug to total weight) oral powder formulations relative to the 100 mg tablet; and (3) oral powder formulations administered using different vehicles (apple juice, apple sauce, and yogurt) relative to water under fed conditions.ResultsBioavailability assessments at a 100 mg dose of venetoclax demonstrated bioequivalence across the 10, 50, and 100 mg tablet strengths. Oral powder formulations met the bioequivalence criteria (0.80-1.25) with respect to area under the concentration-time curve to time of the last measurable concentration (AUCt) and to infinite time (AUC∞) but exhibited a slightly lower maximum plasma concentration (Cmax). Exposure-response analyses were utilized to demonstrate that the lower Cmax observed with the powder formulations is not clinically meaningful. The delivery vehicles tested did not affect the bioavailability of venetoclax oral powder formulations.ConclusionsThe smaller-sized tablets (10 and 50 mg) and the newly developed oral powder formulations of venetoclax can be used interchangeably with the 100 mg tablets to improve the patients' experience, while maintaining adequate exposure. CLINICAL TRIALS IDENTIFIERS: NCT01682616, 11 September 2012; NCT02005471, 9 December 2013; NCT02242942, 17 September 2014; NCT02203773, 30 July 2014; NCT02287233, 10 November 2014; NCT02993523, 15 December 2016; NCT03069352, 3 March 2017.

Dataset Information

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

Publications

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

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