Stetson P L, Shukla U A, Ensminger W D
Upjohn Center for Clinical Pharmacology, University of Michigan Medical School, Ann Arbor 48109.
J Chromatogr. 1989 Feb 17;464(1):163-71. doi: 10.1016/s0021-9673(00)94232-8.
A prerequisite for the prolonged infusion of a drug via a totally implanted drug delivery system is that the drug solution must be sufficiently stable at physiological temperatures to endure the time intervals between drug replacement or pump refills. Consequently, the stability of the chemotherapeutic agents can influence the dosing accuracy and ultimately the achievement of the desired therapeutic goal. The chemical stability of the pharmaceutical preparation Trimetrexate (TMQ) glucuronate, a non-classical, lipophilic antifolate, has been characterized. Incubation of TMQ (prepared in sterile water to a concentration of 5.0 mg/ml) in sterile, amber glass vials at 37 degrees C for 56 days resulted in a degradation rate constant of 0.0134 +/- 0.002 day-1 and a half-life of 51.6 +/- 0.8 days. The major degradation product has been identified as (2,4-diamino-5-methyl-6-carboxaldehyde)quinazoline. Ten percent TMQ degradation would occur by 7.9 days of incubation under these conditions.
通过完全植入式给药系统长时间输注药物的一个前提条件是，药物溶液在生理温度下必须足够稳定，以承受药物更换或泵重新填充之间的时间间隔。因此，化疗药物的稳定性会影响给药准确性，并最终影响预期治疗目标的实现。已对非经典亲脂性抗叶酸药物曲美沙特（TMQ）葡糖醛酸酯制剂的化学稳定性进行了表征。将TMQ（在无菌水中配制成浓度为5.0mg/ml）在无菌琥珀色玻璃瓶中于37℃孵育56天，降解速率常数为0.0134±0.002天⁻¹，半衰期为51.6±0.8天。主要降解产物已鉴定为（2,4-二氨基-5-甲基-6-甲酰基）喹唑啉。在这些条件下孵育7.9天会发生10%的TMQ降解。
