Paul-Ehrlich-Institut (Federal Institute for Vaccines and Biomedicines), Paul-Ehrlich-Straße 7, 63225, Langen, Germany.
Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Henkestrasse 9-11, 91054, Erlangen, Germany.
Arch Toxicol. 2019 Oct;93(10):2787-2796. doi: 10.1007/s00204-019-02561-z. Epub 2019 Sep 14.
Aluminium (Al) toxicokinetics after intramuscular (IM) injection of Al-adjuvanted vaccines is unknown. Since animal data are required for modeling and extrapolation, a rat study was conducted measuring Al in plasma and tissues after IM injection of either plain Al-hydroxide (pAH) or Al-phosphate (pAP) adjuvant (Al dose 1.25 mg), single human doses of three Al-adjuvanted vaccines (V1, V2, and V3; Al doses 0.5-0.82 mg), or vehicle (saline). A significant increase in Al plasma levels compared to controls was observed after pAP (AUC, mean ± SD: 2424 ± 496 vs. 1744 ± 508 µg/L*d). Percentage of Al dose released from injected muscle until day 80 was higher after pAP (66.9%) and AP-adjuvanted V3 (85.5%) than after pAH and AH-adjuvanted V1 (0 and 22.3%, resp.). Estimated absolute Al release was highest for pAP (836.8 µg per rat). Al concentration in humerus bone was increased in all groups, again strongest in the pAP group [3.35 ± 0.39 vs. 0.05 ± 0.06 µg/g wet weight (ww)]. Extrapolated amounts in whole skeleton corresponded to 5-12% of the released Al dose. Very low brain Al concentrations were observed in all groups (adjuvant group means 0.14-0.29 µg/g ww; control 0.13 ± 0.04 µg/g ww). The results demonstrate systemically available Al from marketed vaccines in rats being mainly detectable in bone. Al release appears to be faster from AP- than AH-adjuvants. Dose scaling to human adults suggests that increase of Al in plasma and tissues after single vaccinations will be indistinguishable from baseline levels.
肌肉内注射（IM）含铝佐剂疫苗后铝的毒代动力学尚不清楚。由于需要动物数据进行建模和外推，因此进行了一项大鼠研究，在 IM 注射普通氢氧化铝（pAH）或磷酸铝（pAP）佐剂（铝剂量 1.25mg）、三种含铝佐剂疫苗（V1、V2 和 V3；铝剂量 0.5-0.82mg）或载体（生理盐水）的单次人体剂量后，测量血浆和组织中的铝。与对照组相比，pAP 后观察到铝血浆水平显著升高（AUC，均值±标准差：2424±496 比 1744±508μg/L*d）。pAP（66.9%）和 AP 佐剂 V3（85.5%）从注射肌肉中释放的铝剂量百分比高于 pAH 和 AH 佐剂 V1（0 和 22.3%）。pAP 释放的估计绝对铝量最高（每只大鼠 836.8μg）。所有组的肱骨骨中铝浓度均增加，pAP 组最强[3.35±0.39 比 0.05±0.06μg/g 湿重（ww）]。整个骨骼中推算的量相当于释放的铝剂量的 5-12%。所有组的脑铝浓度都非常低（佐剂组平均值 0.14-0.29μg/g ww；对照组 0.13±0.04μg/g ww）。结果表明，大鼠体内可检测到市售疫苗中的系统性铝主要存在于骨骼中。AP 佐剂释放的铝似乎比 AH 佐剂更快。剂量外推至成人提示单次接种后血浆和组织中铝的增加将与基线水平无法区分。
