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小児病棟における注射薬混合調製では投与量が1製剤単位よりも少ない処方が多数を占め, 正確な薬液の秤取が要求される。凍結乾燥薬においては比例換算により必要量を採取するが, 溶解後に液量が増加する薬剤では過少投与の可能性がある。今回, 液量増加による実投与量への影響を検証した。
①2017年3～4月において調製件数が多い上位7剤(SBT/ABPC, CEZ, CMZ, CAZ, TAZ/PIPC, TEIC, VCM)を検証対象とした。7剤中添付文書に増加液量の記載がある薬剤はTAZ/PIPCのみであった。また, 特に血中濃度のコントロールが必要なTEIC, VCMにおいては製薬会社間での相違を検討するため, 同一成分製品(TEIC5品, VCM2品)についても対象とした。
②生理食塩液10mLで溶解した後の増加液量を測定した。TAZ/PIPCを除き, 最も増加液量の大きい薬剤はSBT/ABPCで約1.57mLであった。
③1バイアルを規定液量に溶解した場合(前秤量)と, 溶解後に規定液量にした場合(後秤量)の薬物濃度を吸光光度計にて測定したところ, 全体的に理論値よりも低い結果となった。これは測定誤差によるものと判断し, 体積の実測から推測される濃度をより正確と考え, 続いての検討を行った。
④前秤量時の液量増加を考慮した投与量を実値, 後秤量時の投与量を理論値として, 溶解方法を検討した。現在は簡便な方法である前秤量にて調製を行っている。10mLで調製する際の投与量の誤差はSBT/ABPC-13.5%, CMZ-11.2%, CAZ-11.2%, CEZ-10.7%, VCM-9.9%, TEIC-6.8%の順であった。4剤は誤差-10%超となり, 過少投与のリスクが大きいと言える。ただし, 今回は手技による影響を最少とすべく10mLで測定したが, 実業務では20mLで計算することが多い。その場合の誤差は最も大きいSBT/ABPCで-7.3%と±10%以内であり, 溶解液量20mL以上では前秤量での調製が許容されると判断した。しかし, 液量減量の際には後秤量が望ましく, 今後の検討が必要である。また, TAZ/PIPCについては3mL増加すると仮定して秤取液量の計算を行っている。これを理論値とした際の誤差は-3.1%であり, 現調製方法で問題ないと考えた。
In the preparation of medications for injection, a single-dose volume for pediatric patients is usually smaller than for adult patients, which requires accurate weighing for medicinal solution. In freeze-dried products, the necessary quantity is obtainable by proportionally adjusting the medications, but underdosing may occur when the liquid volume increases after dissolution. Here, we verified the effect of an increase in liquid volume on the actual drug dose.
①The top 7 most prepared medications in March/April 2017 (SBT/ABPC,CEZ,CMZ,CAZ,TAZ/PIPC,TEIC,and VCM) were verified in this study. Of 7 medication package inserts, only one TAZ/PIPC contained information about the increased amount of liquid after dissolution. Regarding TEIC and VCM that require control of serum medication concentrations, 5 and 2 identical ingredients in TEIC and VCM, respectively, were also included in this study in order to examine differences among pharmaceutical companies.
②We measured the increased amount of liquid after having been dissolved in 10 mL physiological saline. The largest increase in liquid volume except TAZ/PIPC was SBT/ABPC (approximately 1.57 mL).
③Medication concentrations, when one vial was dissolved in the prescribed liquid volume (before weighing or pre-weighing) and when the prescribed liquid volume was reached after dissolution (after weighing or post-weighing), were measured by absorptiometer. Overall, the results were lower than the theoretical values, which was considered to be due to measurement errors ; therefore, we assumed that concentration estimated by the actually measured volume is more accurate, and the following study was conducted.
④A dissolution method was examined based on actual value (defined as drug dose determined by the estimated increase in liquid volume before weighing) and theoretical value (defined as drug dose determined after weighing). Pre-weighing, or in other word, an easy-to-use method, is currently used in preparing medications. Measurement errors of drug dose which occurred in preparing medications by 10 mL physiological saline were 13.5% for SBT/ABPC, 11.2% each for CMZ and CAZ, 10.7% for CEZ, 9.9% for VCM, and 6.8% for TEIC. The risk of underdosing in 4 medications, whose measurement errors exceeded 10%, seems to be high. Although in this study, 10 mL physiological saline was used in preparing medications for minimizing the effects of procedure, 20 mL physiological saline was often used in actual practice. In such a case, the largest measurement error was -7.3% for SBT/ABPC, which falls within the range of ±10% ; therefore, we determined that in more than 20 mL of physiological saline, preparation before weighing is acceptable. However, post-weighing is recommended in a decrease of physiological saline. From this point of view, further studies are needed. In TAZ/PIPC, the amount of liquid is calculated after the increase has been assumed to be 3 mL. When considering this as theoretical value, the measurement error is -3.1% ; therefore, we thought that there is no problem with the current preparation method.