L-システインが引き起こす注射用メロペネムとアミノ酸輸液製剤の配合変化

After meropenem hydrate (MEPM) injection and amino acid infusions are mixed, the MEPM residual ratio sequentially decreases. This incompatibility is probably due to the nucleophilic attack on the β-lactam ring of MEPM by L-cysteine (L-Cys) present in the amino acid infusion. This study aims to identify the influence of L-Cys on the reaction between MEPM injection and amino acid infusions through an initial incompatibility test between MEPM and L-Cys at pH 4 to 8, followed by an incompatibility test between MEPM injection (MEPM plus additives) and 18 types of amino acid infusions. In the MEPM and L-Cys incompatibility test, as the pH increased, the MEPM decomposition speed was observed to increase after mixing of the two components. This reaction progressed as a secondary reaction, the linear relationship between pH and the logarithm of secondary reaction speed constant, k₂, was established (ln k₂ = 1.632 × pH － 15.631, r² = 0.998). In the incompatibility test between MEPM injection and amino acid infusions, as the concentration of L-Cys increased, the MEPM residual ratio was observed to decrease. At 10 and 30 minutes after the mixture of components, a strong correlation was observed between the estimated MEPM residual ratio from the reaction velocity and the measured value (10 minutes: r² = 0.985, RMSE: 5.44％; 30 minutes: r² = 0.986，RMSE: 4.55％). The results above indicate that the residual ratio of MEPM obtained through the L-Cys incompatibility test matches the measured residual ratio of MEPM using the MEPM injection and amino acid infusions. Therefore, L-Cys has been identified as the main cause of incompatibility between MEPM injection and amino acid infusions.