Bailey Damian Miles, Stacey Benjamin S, Gumbleton Mark
1 Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales , Mid-Glamorgan, United Kingdom .
2 School of Pharmacy and Pharmaceutical Sciences, Cardiff University , Cardiff, United Kingdom .
High Alt Med Biol. 2018 Jun;19(2):141-148. doi: 10.1089/ham.2017.0121. Epub 2018 Apr 5.
Bailey, Damian Miles, Benjamin S. Stacey, and Mark Gumbleton. A systematic review and meta-analysis reveals altered drug pharmacokinetics in humans during acute exposure to terrestrial high altitude-clinical justification for dose adjustment? High Alt Med Biol. 19:141-148, 2018.
While physiological responses during acute ascent to terrestrial high altitude (HA) have the potential to alter the pharmacokinetics (PKs) that define absorption and disposition of medicinal drugs, there have been no systematic reviews and meta-analyses performed to date.
We conducted a systematic literature search in June 2017 using NCBI PubMed, EMBASE, Web of Science, and Ovid MEDLINE databases to identify relevant observational studies. Studies were deemed eligible based on the following criteria: (1) participants: healthy, nonacclimatized male or female lowlanders (born and bred at sea level) and (2) environment: exposure to low altitude (LA, ≤600 m), followed by terrestrial high altitude (HA, ≤24 hours to ≥2500 m), the time course specifically selected to avoid interpretive complications associated with erythrocytosis. All PK parameters were standardized to be in the same units and the weighted standardized mean difference (SMD) calculated using a combination of fixed and random effects models with heterogeneity evaluated using χ and I statistics.
Of 20,840 studies reviewed, 6 prospective cohort studies (n = 75) qualified for inclusion, with participants exposed to a mean altitude of 4025 (mean) ± 380 (SD) m. We observed increases for absorption half-life (SMD: 0.40, 95% CI: 0.01-0.80, p = 0.04], elimination half-life (SMD: 0.89, 95% CI: 0.30-1.48, p = 0.003), and erythrocyte binding (SMD: 0.52, 95% CI: 0.16-0.88, p = 0.004) and reduction in clearance (SMD: -0.56, 95% CI: -1.13 to 0.00, p = 0.05).
Collectively, these findings reveal impairments in both oral absorption and corresponding clearance of the, although limited, sample of drugs at HA that may potentially require closer patient monitoring and dose adjustments to maintain therapeutic efficacy and avoid incidental toxicity.
贝利，达米安·迈尔斯，本杰明·S·斯泰西，以及马克·冈布尔顿。一项系统评价和荟萃分析显示，人类在急性暴露于陆地高海拔环境期间药物药代动力学发生改变——剂量调整的临床依据？《高海拔医学与生物学》。2018年第19卷，第141 - 148页。
虽然急性上升至陆地高海拔（HA）期间的生理反应有可能改变定义药物吸收和处置的药代动力学（PKs），但迄今为止尚未进行系统评价和荟萃分析。
我们于2017年6月使用美国国立医学图书馆（NCBI）的PubMed、EMBASE、科学网和Ovid MEDLINE数据库进行了系统的文献检索，以识别相关的观察性研究。根据以下标准，研究被视为合格：（1）参与者：健康、未适应环境的男性或女性低地居民（出生并成长于海平面）；（2）环境：先暴露于低海拔（LA，≤600米），随后暴露于陆地高海拔（HA，≤24小时至≥2500米），特意选择该时间进程以避免与红细胞增多症相关的解释复杂性。所有PK参数均标准化为相同单位，并使用固定效应模型和随机效应模型相结合的方法计算加权标准化均值差（SMD），使用χ²和I²统计量评估异质性。
在审查的20,840项研究中，有6项前瞻性队列研究（n = 75）符合纳入标准，参与者暴露于平均海拔4025（均值）±380（标准差）米的环境。我们观察到吸收半衰期增加（SMD：0.40，95%置信区间：0.01 - 0.80，p = 0.04）、消除半衰期增加（SMD：0.89，95%置信区间：0.30 - 1.48，p = 0.003）、红细胞结合增加（SMD：0.52，95%置信区间：0.
