Relative Bioavailability of Orally Dispersible Tablet Formulations of Levo‐ and Racemic Praziquantel: Two Phase I Studies
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.12601 |
| _version_ | 1811228366039154688 |
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| author | Wilhelmina Maria Bagchus Deon Bezuidenhout Eleanor Harrison‐Moench Elly Kourany‐Lefoll Peter Wolna Oezkan Yalkinoglu |
| author_facet | Wilhelmina Maria Bagchus Deon Bezuidenhout Eleanor Harrison‐Moench Elly Kourany‐Lefoll Peter Wolna Oezkan Yalkinoglu |
| author_sort | Wilhelmina Maria Bagchus |
| collection | DOAJ |
| description | 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). |
| first_indexed | 2024-04-12T09:56:29Z |
| format | Article |
| id | doaj.art-936d038baeca4aaf9835448040d0e918 |
| institution | Directory Open Access Journal |
| issn | 1752-8054 1752-8062 |
| language | English |
| last_indexed | 2024-04-12T09:56:29Z |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj.art-936d038baeca4aaf9835448040d0e9182022-12-22T03:37:40ZengWileyClinical and Translational Science1752-80541752-80622019-01-01121667610.1111/cts.12601Relative Bioavailability of Orally Dispersible Tablet Formulations of Levo‐ and Racemic Praziquantel: Two Phase I StudiesWilhelmina Maria Bagchus0Deon Bezuidenhout1Eleanor Harrison‐Moench2Elly Kourany‐Lefoll3Peter Wolna4Oezkan Yalkinoglu5Quantitative Pharmacology Merck Institute for Pharmacometrics (an affiliate of Merck KGaA, Darmstadt, Germany) Lausanne SwitzerlandMerck KGaA Modderfontein South AfricaQuantitative Pharmacology Merck KGaA Darmstadt GermanyGlobal Health Institute Ares Trading S.A. Coinsins SwitzerlandGlobal Biostatistics Merck KGaA Darmstadt GermanyQuantitative Pharmacology Merck KGaA Darmstadt GermanyOrally 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).https://doi.org/10.1111/cts.12601 |
| spellingShingle | Wilhelmina Maria Bagchus Deon Bezuidenhout Eleanor Harrison‐Moench Elly Kourany‐Lefoll Peter Wolna Oezkan Yalkinoglu Relative Bioavailability of Orally Dispersible Tablet Formulations of Levo‐ and Racemic Praziquantel: Two Phase I Studies Clinical and Translational Science |
| title | Relative Bioavailability of Orally Dispersible Tablet Formulations of Levo‐ and Racemic Praziquantel: Two Phase I Studies |
| title_full | Relative Bioavailability of Orally Dispersible Tablet Formulations of Levo‐ and Racemic Praziquantel: Two Phase I Studies |
| title_fullStr | Relative Bioavailability of Orally Dispersible Tablet Formulations of Levo‐ and Racemic Praziquantel: Two Phase I Studies |
| title_full_unstemmed | Relative Bioavailability of Orally Dispersible Tablet Formulations of Levo‐ and Racemic Praziquantel: Two Phase I Studies |
| title_short | Relative Bioavailability of Orally Dispersible Tablet Formulations of Levo‐ and Racemic Praziquantel: Two Phase I Studies |
| title_sort | relative bioavailability of orally dispersible tablet formulations of levo and racemic praziquantel two phase i studies |
| url | https://doi.org/10.1111/cts.12601 |
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