| Popis: |
ラット頬部カラゲニン炎症モデルを用いて, その急性期 (1日目) および慢性期 (5日目) に抗菌薬 (PIPC, CTRX) を種々の量で, かつ静脈内一括投与あるいは持続点滴投与して頬部膿瘍内浸出液および周囲肉芽組織への移行性を検討し, 以下の結果を得た。1) PIPCの血清, 浸出液および肉芽組織内濃度のCmaxとAUCは, 用量反応性に上昇したが, T1/2に変化はなかった。2) 血清PIPC濃度のAUC上昇は, 投与量に正比例していたが, 肉芽組織と浸出液のAUCの変化は, 投与量が2倍になると肉芽組織では約1.5倍, 浸出液では約1.3倍の増加率であった。3) 炎症時期別に肉芽組織の抗菌薬AUCをみると, 1日目が5日目の約2倍良好な移行性を示したが, 投与量を増加しても比率は一定であった。4) 点滴静注においても one shot 静注と同様に, 浸出液内抗菌薬濃度は長時間持続したが, 肉芽組織ではピーク以後血清と類似した濃度推移をとった。5) 投与方法別に肉芽組織のAUCをみると, PIPCでは点滴静注の方が高値を示したが, CTRXでは逆に one shot 静注の方がAUCは大きい結果であった。以上の成績より, 炎症組織内抗菌薬濃度は血清と同様の時間的推移をとるが, 投与量の増加は必ずしもそのまま炎症組織内濃度に反映されず, また半減期にも変化がみられなかったことから, 投与間隔に対する配慮も必要と考えられた。また, 投与方法による比較では, 半減期の短い薬剤ほど持続投与の有用性が高く, 半減期の長い薬剤では one shot 静注でも十分な炎症組織内濃度が維持される可能性が示唆された。 / The penetration of antibiotics to the exudate and granulation tussue of buccal abscess induced by carrageenin in rats was examined in the different inflammatory stages (day 1 : acute, day 5 : chronic) to clarify the correlation between inflammatory tissue levels and dosage of PIPC (20, 40, 80mg/kg, i.v.) as well as the difference of antibiotics concentration in tissues by either i.v.or d.i.v.of 20mg/kg PIPC and CTRX. The results were as follows. 1) After i.v. administration of PIPC, Cmax and AUC of PIPC concentrations in the serum, exudate and granulation tissue dose-dependently increased, whereas their T1/2 was not different irrespective of the dosage. 2) AUC of antibiotics concentration in the serum was increased in the same proportion as the dosage increased, whereas its AUC increased 1.5 fold in the granulation tissue and 1.3 fold in the exudate when the dosage was twice as much. 3) AUC in the granulation tissue was bigger on day 1 than day 5, but increased with the same proportion of the dosage regardless of imflammatory stages. 4) Irrespective of i.v. and d.i.v. injection, antibiotics levels in the exudate sustained longer than those of the serum, and the concentrations in granulation tissue were decreased similaly to serum levels after its peak of concentration . 5) AUC of PIPC in the granulation tissue after d.i.v. injection was 1.5-2.0 fold higher than that after i.v., while AUC of CTRX showed the opposite to PIPC. From the above results, the concentrations of granulation tissue correlates well with the serum levels, however, the increase of the dosage did not reflect AUC in the granulation tissue, and T1/2 was not changed. Therefor it was considered that the proper intervals of administion should be made. It was also suggested that in antibiotics with lower protein binding rate like PIPC a continuous administration would be usefull and in antibiotics with higher protein binding rate like CTRX the levels of inflammatory tissue would be maintained well even on one shot i.v.. |
