Dalton J T, Zhou D, Mukherjee A, Young D, Tolley E A, Golub A L, Meyer M C
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis 38163, USA.
Pharm Res. 1999 Feb;16(2):288-95. doi: 10.1023/a:1018840827910.
To examine the stability and systemic absorption of aminolevulinic acid (ALA) in dogs during intravesical administration.
Nine dogs received an intravesical dose of ALA either with no prior treatment, after receiving ammonium chloride for urinary acidification, or after receiving sodium bicarbonate for urinary alkalinization. Urine and blood samples collected during and after administration were monitored for ALA using an HPLC assay developed in our laboratories. Concentrations of pyrazine 2,5-dipropionic acid, the major ALA degradation product, and radiolabeled inulin, a nonabsorbable marker for urine volume, were also determined.
Less than 0.6% of intravesical ALA doses was absorbed into plasma. Urine concentrations decreased to 37% of the initial concentration during the 2 hour instillation. Decreases in urinary ALA and radiolabeled inulin concentrations were significantly correlated, indicating that urine dilution accounted for over 80% of observed decreases in urinary ALA. ALA conversion to pyrazine 2,5-dipropionic acid was negligible.
These studies demonstrate that ALA is stable and poorly absorbed into the systemic circulation during intravesical instillation. Future studies utilizing intravesical ALA for photodiagnosis of bladder cancer should include measures to restrict fluid intake as a means to limit dilution and maximize ALA concentrations during instillation.
研究氨基乙酰丙酸（ALA）在犬膀胱内给药期间的稳定性及全身吸收情况。
9只犬分别在未进行预处理、接受氯化铵使尿液酸化或接受碳酸氢钠使尿液碱化后接受膀胱内给予的ALA剂量。使用我们实验室开发的高效液相色谱法（HPLC）测定给药期间及给药后采集的尿液和血液样本中的ALA。还测定了主要的ALA降解产物吡嗪2,5 - 二丙酸的浓度以及放射性标记的菊粉（一种尿液体积的不可吸收标记物）的浓度。
膀胱内给予的ALA剂量中，吸收进入血浆的比例不到0.6%。在2小时滴注期间，尿液浓度降至初始浓度的37%。尿液中ALA和放射性标记菊粉浓度的降低显著相关，表明尿液稀释占观察到的尿液中ALA降低的80%以上。ALA转化为吡嗪2,5 - 二丙酸的量可忽略不计。
这些研究表明，在膀胱内滴注期间，ALA是稳定的，且全身吸收较差。未来利用膀胱内给予ALA进行膀胱癌光诊断的研究应包括限制液体摄入的措施，以此作为在滴注期间限制稀释并使ALA浓度最大化的一种手段。
