Jose Manuel Del Moral Sanchez1,2, Isabel Gonzalez-Alvarez2, Aaron Cerda-Revert2, Marta Gonzalez-Alvarez2, Andres Navarro-Ruiz3, Gordon L Amidon4, Marival Bermejo2. 1. Institute of Molecular and Cellular Biology of Miguel Hernandez University, Avda de la Universidad s/n, 03202, Elche (Alicante), Spain. 2. Department of Pharmacokinetics and Pharmaceutical Technology, Miguel Hernandez University, San Juan de Alicante, 03550, Alicante, Spain. 3. Pharmacy Service, General University Hospital of Elche, 03202, Elche (Alicante), Spain. 4. University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI, 48109-1065, USA.
Abstract
AIMS: Unavailability 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). METHODS: Albendazole, 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 log P comparison versus metoprolol log P 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. RESULTS: All 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. CONCLUSION: Provisional 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.
AIMS: Unavailability 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). METHODS:Albendazole, 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 log P comparison versus metoprolol log P 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. RESULTS: All 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. CONCLUSION: Provisional 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.
Authors: Nehal A Kasim; Marc Whitehouse; Chandrasekharan Ramachandran; Marival Bermejo; Hans Lennernäs; Ajaz S Hussain; Hans E Junginger; Salomon A Stavchansky; Kamal K Midha; Vinod P Shah; Gordon L Amidon Journal: Mol Pharm Date: 2004-01-12 Impact factor: 4.939
Authors: Leonie Hussaarts; Kim van der Weijde; Pierre Dome; Elly Kourany-Lefoll; Jutta Reinhard-Rupp; Remco de Vrueh Journal: PLoS Negl Trop Dis Date: 2017-02-23
Authors: Jose Manuel Del Moral Sanchez; Isabel Gonzalez-Alvarez; Aaron Cerda-Revert; Marta Gonzalez-Alvarez; Andres Navarro-Ruiz; Gordon L Amidon; Marival Bermejo Journal: Br J Clin Pharmacol Date: 2018-07-17 Impact factor: 4.335