Biopharmaceutical optimization in neglected diseases for paediatric patients by applying the provisional paediatric biopharmaceutical classification system
Por:
del Moral Sanchez, J, Gonzalez-Alvarez, I, Cerda-Revert, A, Gonzalez-Alvarez, M, Navarro-Ruiz, A, Amidon, G and Bermejo, M
Publicada:
1 oct 2018
Resumen:
AimsUnavailability and lack of appropriate, effective and safe formulations are common problems in paediatric therapeutics. Key factors such as swallowing abilities, organoleptic preferences and dosage requirements determine the need for optimization of formulations. The provisional Biopharmaceutics Classification System (BCS) can be used in paediatric formulation design as a risk analysis and optimization tool. The objective of this study was to classify six neglected tropical disease drugs following a provisional paediatric BCS (pBCS) classification adapted to three paediatric subpopulations (neonates, infants and children).
MethodsAlbendazole, benznidazole, ivermectin, nifurtimox, praziquantel and proguanil were selected from the 5th edition of the Model List of Essential Medicines for Children from the World Health Organization. Paediatric drug solubility classification was based on dose number calculation. Provisional permeability classification was based on logP comparison versus metoprolol logP value, assuming passive diffusion absorption mechanisms and no changes in passive membrane permeability between paediatric patients and adults. pBCS classes were estimated for each drug, according to different doses and volumes adapted for each age stage and were compared to the adult classification.
ResultsAll six drugs were classified into provisional pBCS in the three paediatric subpopulations. Three drugs maintained the same classification as for adults, ivermectin and benznidazole changed solubility class from low to high in neonates and proguanil changed from low to high solubility in all age stages.
ConclusionProvisional pBCS classification of these six drugs shows potential changes in the limiting factors in oral absorption in paediatrics, depending on age stage, compared to the adult population. This valuable information will aid the optimization of paediatric dosing and formulations and can identify bioinequivalence risks when comparing different formulations and paediatric populations.
Filiaciones:
del Moral Sanchez, J:
Miguel Hernandez Univ, Inst Mol & Cellular Biol, Avda Univ S-N, Elche 03202, Alicante, Spain
Miguel Hernandez Univ, Dept Pharmacokinet & Pharmaceut Technol, Alicante 03550, Spain
Gonzalez-Alvarez, I:
Miguel Hernandez Univ, Dept Pharmacokinet & Pharmaceut Technol, Alicante 03550, Spain
Cerda-Revert, A:
Miguel Hernandez Univ, Dept Pharmacokinet & Pharmaceut Technol, Alicante 03550, Spain
Gonzalez-Alvarez, M:
Miguel Hernandez Univ, Dept Pharmacokinet & Pharmaceut Technol, Alicante 03550, Spain
:
Gen Univ Hosp Elche, Pharm Serv, Elche 03202, Alicante, Spain
Amidon, G:
Univ Michigan, Coll Pharm, 428 Church St, Ann Arbor, MI 48109 USA
Bermejo, M:
Miguel Hernandez Univ, Dept Pharmacokinet & Pharmaceut Technol, Alicante 03550, Spain
Green Published, Bronze
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