Tishler P V, Gordon B J
Methods Find Exp Clin Pharmacol. 1983;5(3):185-91.
We studied the ability of a commercial charcoal hemoperfusion cartridge (Hemosorba Hemoperfusion Cartridge, Asahi Medical Company) to adsorb the porphyrin precursors delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) in vitro. For measurement of clearances or decreases in concentration of porphyrin precursor, indices of adsorptivity, solutions of porphyrin precursor were circulated from a reservoir through the cartridge and back to the reservoir. For determination of change in concentration of porphyrin precursor with time, the concentration of material in the reservoir was determined periodically. Clearances of porphyrin precursor were determined from their concentration in both the reservoir (maintained nearly constant by the periodic addition of solute) and the cartridge effluent. Clearances were independent of the nature of the medium (saline, 0.1 M phosphate buffer, pH 7.4, or human plasma), time (through 2 hr) and initial concentration of porphyrin precursor (3.0-10.3 mg/L for ALA, 1.5-3.6 mg/L for PBG). ALA clearances (ml/min) were 106 +/- 22, while maximal PBG clearances were never ascertained (greater than or equal to 310). The concentration of porphyrin precursor decreased rapidly during perfusion: about 82% and 98% of ALA and PBG, respectively, were removed in 5 minutes. Neither the clearances nor the concentration decreases were affected by the simultaneous presence in the solution of hematin (initial concentration of 50 mg/L), which itself had a clearance of 10.7 +/- 12.6 and only a modest concentration change with time (60-68% decrease in 40 min). Hemosorba cartridges adsorbed 650 mg ALA and 85 mg PBG without any appreciable change in adsorptivity. Hemoperfusion may be an appropriate adjunctive therapy, in combination with infusions of hematin, of particularly severe or refractory acute porphyric crises.
我们研究了一种商用活性炭血液灌流柱(旭化成医疗公司的血液吸附灌流柱)在体外吸附卟啉前体δ-氨基乙酰丙酸(ALA)和卟胆原(PBG)的能力。为了测量卟啉前体的清除率或浓度降低情况、吸附性指标,将卟啉前体溶液从储液器循环通过灌流柱再回到储液器。为了测定卟啉前体浓度随时间的变化,定期测定储液器中物质的浓度。根据储液器(通过定期添加溶质使其浓度几乎保持恒定)和灌流柱流出液中卟啉前体的浓度来确定其清除率。清除率与介质性质(生理盐水、0.1 M pH 7.4的磷酸盐缓冲液或人血浆)、时间(长达2小时)以及卟啉前体的初始浓度(ALA为3.0 - 10.3 mg/L,PBG为1.5 - 3.6 mg/L)无关。ALA的清除率(ml/min)为106±22,而PBG的最大清除率尚未确定(≥310)。灌流过程中卟啉前体浓度迅速下降:5分钟内分别约82%的ALA和98%的PBG被清除。溶液中同时存在血晶素(初始浓度为50 mg/L)时,清除率和浓度降低情况均未受影响,血晶素本身的清除率为10.7±12.6,且随时间浓度变化不大(40分钟内降低60 - 68%)。血液吸附灌流柱吸附了650 mg ALA和85 mg PBG,吸附性无明显变化。血液灌流结合血晶素输注可能是治疗特别严重或难治性急性卟啉危象的一种合适辅助疗法。