Personalised dosing of medicines for children

Al-Metwali, Basma Zuheir; Mulla, Hussain

doi:10.1111/jphp.12709

Cited by 28 publications

(24 citation statements)

References 85 publications

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“…Providing patients and clinicians with the least complex warfarin therapy possible would improve the medical errors associated with medication administration and usage and decrease the practical challenges involved in implementing complex therapy protocols in every day clinical settings. 27–30 Furthermore, providing patients with the least complex possible warfarin therapy, including once daily prescriptions and no cut pills can increase protocol adherence, increase TTR and improve patient satisfaction. 28 …”

Section: Discussionmentioning

confidence: 99%

“…Protocol complexity has important implications for patient satisfaction, protocol adherence, cost-effectiveness and potentially clinical outcomes. 27–30 We quantified the degree of complexity by counting the number of demographic, clinical, and genetic variables used to personalize warfarin dose and the number of INR-based thresholds used to adjust the dose. The sum of these two counts was aggregated into a “Complexity Score” for each protocol.…”

Section: Methodsmentioning

confidence: 99%

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Personalized Anticoagulation

Ravvaz

Weissert

Ruff

et al. 2017

Circ Cardiovasc Genet

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Background Clinical trials testing pharmacogenomic-guided (PG-guided) warfarin dosing for patients with atrial fibrillation(AF) have demonstrated conflicting results. Non-vitamin K antagonist oral anticoagulants (NOACs) are expensive and contraindicated for several conditions. A strategy optimizing anticoagulant selection remains an unmet clinical need. Methods and Results Characteristics from 14,206 patients with AF were integrated into a validated warfarin clinical trial simulation framework using iterative Bayesian network modeling and a pharmacokinetic–pharmacodynamic model. Individual dose response for patients was simulated for five warfarin protocols – a fixed-dose protocol, a clinically guided protocol and three increasingly complex PG-guided protocols. For each protocol a complexity score was calculated using the variables predicting warfarin dose and the number of predefined INR thresholds for each adjusted dose. Study outcomes included optimal time in therapeutic range (TTR) ≥65% and clinical events. A combination of age and genotype identified different optimal protocols for various subpopulations. A fixed-dose protocol provided well-controlled INR only in normal responders ≥65, while for normal responders <65 years old, a clinically guided protocol was necessary to achieve well-controlled INR. Sensitive responders ≥65 and <65 and highly sensitive responders ≥65 years old required PG-guided protocols to achieve well-controlled INR. However, highly sensitive responders <65 years old, did not achieve well-controlled INR and had higher associated clinical events rates than other subpopulations. Conclusions Under the assumptions of this simulation, patients with AF can be triaged to an optimal warfarin therapy protocol by age and genotype. Clinicians should consider alternative anticoagulation therapy for patients with suboptimal outcomes under any warfarin protocol.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Personalized Anticoagulation

Ravvaz

Weissert

Ruff

et al. 2017

Circ Cardiovasc Genet

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“…MIPD allows prescribers to determine the starting dose before any TDM sample is taken. When TDM measurements become available, MIPD will combine the information from the PK/PD model and individual patient PK characteristics to further personalize the dosing regimen during treatment [145][146][147]. The main advantages of this approach are that target concentrations can be achieved earlier in the course of the drug therapy when compared with classical TDM, and that it can predict future drug concentrations.…”

Section: Model-informed Precision Dosingmentioning

confidence: 99%

Optimizing the Use of Antibiotic Agents in the Pediatric Intensive Care Unit: A Narrative Review

et al. 2020

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“…Pharmaceuticals are predominantly produced according to a centralized and time-consuming batch processing approach [1]. This supply chain model allows production of only a few dose strengths in large volumes, which for the blockbuster drugs are chosen based on population level information [2]. Challenges may arise if a patient is treated with an active pharmaceutical ingredient (API) with a narrow therapeutic window or a varying pharmacokinetic or pharmacodynamic profile.…”

Section: Introductionmentioning

confidence: 99%

Stencil Printing—A Novel Manufacturing Platform for Orodispersible Discs

et al. 2020

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Stencil printing is a commonly used printing method, but it has not previously been used for production of pharmaceuticals. The aim of this study was to explore whether stencil printing of drug containing polymer inks could be used to manufacture flexible dosage forms with acceptable mass and content uniformity. Formulation development was supported by physicochemical characterization of the inks and final dosage forms. The printing of haloperidol (HAL) discs was performed using a prototype stencil printer. Ink development comprised of investigations of ink rheology in combination with printability assessment. The results show that stencil printing can be used to manufacture HAL doses in the therapeutic treatment range for 6–17 year-old children. The therapeutic HAL dose was achieved for the discs consisting of 16% of hydroxypropyl methylcellulose (HPMC) and 1% of lactic acid (LA). The formulation pH remained above pH 4 and the results imply that the drug was amorphous. Linear dose escalation was achieved by an increase in aperture area of the print pattern, while keeping the stencil thickness fixed. Disintegration times of the orodispersible discs printed with 250 and 500 µm thick stencils were below 30 s. In conclusion, stencil printing shows potential as a manufacturing method of pharmaceuticals.

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Personalised dosing of medicines for children

Cited by 28 publications

References 85 publications

Personalized Anticoagulation

Personalized Anticoagulation

Optimizing the Use of Antibiotic Agents in the Pediatric Intensive Care Unit: A Narrative Review

Stencil Printing—A Novel Manufacturing Platform for Orodispersible Discs

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