加巴喷丁和曲马多在儿童慢性疼痛患者中的剂量原理。

IF 2.9 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Paul Healy, Luka Verrest, Mariagrazia Felisi, Adriana Ceci, Oscar Della Pasqua
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引用次数: 0

摘要

尽管标签外使用,加巴喷丁和曲马多在儿科患者中的疗效和安全性(3 月至0-8)约35 mg/L*小时(1200 mg/天成人剂量当量)。曲马多的中位稳态浓度在200和300之间 2-5次给药后达到ng/mL mg/kg,但浓度表现出较高的个体间变异性。模拟场景显示,考虑到两种药物的安全性,需要滴定步骤来探索治疗相关的剂量范围。加巴喷丁可按7-63至5-45的剂量静脉注射使用 mg/kg,用于接受加巴喷丁称重的患者
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Dose rationale for gabapentin and tramadol in pediatric patients with chronic pain.

Dose rationale for gabapentin and tramadol in pediatric patients with chronic pain.

Dose rationale for gabapentin and tramadol in pediatric patients with chronic pain.

Despite off-label use, the efficacy and safety of gabapentin and tramadol in pediatric patients (3 months to <18 years old) diagnosed with chronic pain has not been characterized. However, generating evidence based on randomized clinical trials in this population has been extremely challenging. The current investigation illustrates the use of clinical trial simulations (CTSs) as a tool for optimizing doses and protocol design for a prospective investigation in pediatric patients with chronic pain. Pharmacokinetic (PK) modeling and CTSs were used to describe the PKs of gabapentin and tramadol in the target population. In the absence of biomarkers of analgesia, systemic exposure (AUC, Css) was used to guide dose selection under the assumption of a comparable exposure-response (PKPD) relationship for either compound between adults and children. Two weight bands were identified for gabapentin, with doses titrated from 5 to 63 mg/kg. This yields gabapentin exposures (AUC0-8 ) of approximately 35 mg/L*h (1200 mg/day adult dose equivalent). For tramadol, median steady state concentrations between 200 and 300 ng/mL were achieved after doses of 2-5 mg/kg, but concentrations showed high interindividual variability. Simulation scenarios showed that titration steps are required to explore therapeutically relevant dose ranges taking into account the safety profile of both drugs. Gabapentin can be used t.i.d. at doses between 7-63 and 5-45 mg/kg for patients receiving gabapentin weighing <15 and ≥15 kg, respectively, whereas a t.i.d. regimen with doses between 1 and 5 mg/kg can be used for tramadol in patients who are not fast metabolisers.

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来源期刊
Pharmacology Research & Perspectives
Pharmacology Research & Perspectives Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics
CiteScore
5.30
自引率
3.80%
发文量
120
审稿时长
20 weeks
期刊介绍: PR&P is jointly published by the American Society for Pharmacology and Experimental Therapeutics (ASPET), the British Pharmacological Society (BPS), and Wiley. PR&P is a bi-monthly open access journal that publishes a range of article types, including: target validation (preclinical papers that show a hypothesis is incorrect or papers on drugs that have failed in early clinical development); drug discovery reviews (strategy, hypotheses, and data resulting in a successful therapeutic drug); frontiers in translational medicine (drug and target validation for an unmet therapeutic need); pharmacological hypotheses (reviews that are oriented to inform a novel hypothesis); and replication studies (work that refutes key findings [failed replication] and work that validates key findings). PR&P publishes papers submitted directly to the journal and those referred from the journals of ASPET and the BPS
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