A two-period crossover study on the plasma creatine phosphokinase (CPK) using six male rabbits after intramuscular administration of each 1 ml of 25% (w/v) of sulpyrine (SP) and propylene glycol (PG) neutral pH solutions was carried out to assess the local toxicity of the solutions.
The individual ratio of total CPK liberated (PG/SP) in six rabbits were I.50; 2.43;3.89; 7.16; 1.75 and 1.82 respectively. The analysis of variance revealed a significant difference in the treatment (p < 0.01), in subject and in subject/group (p < 0.05); where-as the variation of different treatment period was insignificant. The results imply that there is large intersubject variability in the liberation of CPK after administration. Macroscopic examination on the injected muscle was carried out to three rabbits for a separate study after four days of intramuscular administration of SP and PG. There was no macroscopic lesion at injection sites, only a tiny hemorrhagic spot of needle puncture in one rabbit was observed.
The results suggest a two-period crossover study using the serial analysis of plasma CPK may be more sensitive and discriminating method than conventional morphological examination in assessing local toxicity of intramuscular solutions. 以二期性交叉實驗法考察肌注25%propylene glycol (PG)及sulpyrine (SP)的中性溶液於六隻家兔後血漿中肌肉型CPK活性的經時變化，使用藥物動力學方法加以解析。
肌注後CPK之總釋離量比(PG/SP)各分別為: 1.50 ； 2.43 ； 3.89 ； 7.16 ； 1.75及1.82。變異數分析結果，處理效應(p<0.01)，個體差，個體/組差(P<0.05)皆明顯地不同。但實驗之前期及後期之時間別沒有有意之差異。此結果表示對同一處置所引起的CPK釋離量有相當大的個體差異。故統計解析宜使用無毋數統計檢定法較適合。
肌注後有極顯著之血漿中CPK活性的昇高(正常值之十倍以上)而且持續三天左右。然而在切開檢視皆未發現任何可視之組織傷害。據此可推論，血漿中肌肉型CPK的活性變化的考察法實比傳統的組織檢查法更靈敏，能評估肌注液的局部毒性，值得應用於臨床前(pre-clinical phase)之處方開發及設計。
因為PG溶液常被使用於肌注液的調製，各種濃度的PG溶液可作為肌注液的局部毒性的對照品。
關聯:
嘉南學報 15 : p.A68-A77 轉載 Journal of the Taiwan pharmacutical association 39(4) 1988
