Pediatric Unit, Department of Women's and Children's Health, Azienda Provinciale Per i Servizi Sanitari, Largo Medaglie d'oro 9, Trento, Italy.
Hospital Pharmacy Unit, Azienda Provinciale Per i Servizi Sanitari, Largo Medaglie d'oro 9, Trento, Italy.
Eur J Pharm Biopharm. 2024 Oct;203:114429. doi: 10.1016/j.ejpb.2024.114429. Epub 2024 Aug 7.
sepiapterine reductase deficiency (SRD) is a rare levodopa (L-dopa)-responsive disorder treated with a combination therapy of controlled-release L-dopa and carbidopa. The currently available formulation of controlled-release carbidopa/L-dopa does not entirely meet the requirements for the long-term therapy in pediatric patients. In fact, administration of a manufactured tablet at a dose intended for adults necessitates its adjustment to the child's needs, as the splitting of the tablet into smaller portions or its dilution in water. It's essential to emphasize that tablets must not be crushed, as this can compromise the controlled-release mechanism and affect the efficacy of the medication. At the moment, commercial liquid formulations are not available. Given these limitations, in house drug preparation in hospitals and community pharmacies is a valid option to ensure the proper therapeutic management of these patients.
we described sample preparation, physical and microbiological analyses, taste testing, and tolerability of a 1:10 ratio carbidopa/L-dopa flavored (mint, raspberry, cacao, berries) and unflavored oral formulation (no sweetening agents were added). We also reported long-term follow-up of two pediatric patients with SRD.
we documented the stability for 28 days at 25 °C of the liquid solution. All formulations were well-tolerated, and no adverse events were observed during or after assessing taste and tolerability. The long-term follow up of two patients was characterized by effective symptom control and optimal treatment adherence and compliance.
in-house liquid drug formulations can be a valid option for pediatric patients with SRD. Given the significant impact of taste on medication adherence, the use of flavoring agents in the development of liquid formulations of L-dopa/carbidopa results a very useful strategy to obtain optimal adherence in the pediatric population.
蝶呤还原酶缺乏症（SRD）是一种罕见的左旋多巴（L-dopa）反应性疾病，采用控释左旋多巴和卡比多巴联合治疗。目前可用的控释卡比多巴/L-dopa 制剂不完全满足儿科患者长期治疗的要求。事实上，将成人剂量的控释卡比多巴/L-dopa 片剂给药时，需要根据儿童的需求进行调整，例如将片剂分成更小的部分或在水中稀释。必须强调的是，片剂不能被压碎，因为这会破坏控释机制并影响药物的疗效。目前，商业上的液体制剂不可用。鉴于这些限制，医院和社区药房内部药物制备是确保这些患者得到适当治疗管理的有效选择。
我们描述了样品制备、物理和微生物分析、口味测试以及 1:10 比例的卡比多巴/L-dopa 调味（薄荷、覆盆子、可可、浆果）和未调味口服制剂（未添加甜味剂）的耐受性。我们还报告了两名 SRD 儿科患者的长期随访结果。
我们记录了在 25°C 下 28 天的液体溶液稳定性。所有制剂均耐受良好，在评估口味和耐受性期间或之后均未观察到不良反应。两名患者的长期随访结果表明症状得到有效控制，治疗依从性和顺应性最佳。
内部液体药物制剂可以作为 SRD 儿科患者的有效选择。鉴于口味对药物依从性的重大影响，在开发左旋多巴/卡比多巴的液体制剂时使用调味剂是获得儿科人群最佳依从性的非常有用的策略。
