シクロスポリンの体内分布の検討－ リンパ系組織への分布－

Abstract

1)対象は生体腎移植の移植前治療として胸管ドレナージによるリンパ球除去を施行した13症例である.CsA 300 mg乃至400 mgを経口投与した場合, 胸管リンパ液中のCsA濃度は血清濃度に比べて著しく高かった.CsA 100 mgを静脈内に投与した場合, 胸管リンパ液中のCsA濃度は全血濃度に比べて低かった.2)腎移植術を施行し, 手術中にリンパ節を採取した20例についてリンパ節組織内のCsA濃度を測定した.リンバ節のCsA濃度は185から7890 ng/ml, 平均3222 ng/gであり, 末梢血からリンパ節への拡散率(CsAリンパ節濃度/末梢血清濃度)は3.9から38.9, 平均17.1であった.拡散率は経口, 静注投与群間に差をみなかった

To clarify the distribution and the kinetics of ciclosporin (CSA) in the lymphatic system, we measured the CSA level of the lymph from the thoracic duct drainage (TDD) and that of the peripheral blood after oral or intravenous administration of CSA in 13 TDD pretreated patients. We also measured the CSA level of the iliac lymph nodes in 20 patients undergoing transplant surgery. The mean CSA level of the lymph was 1, 647 ng/ml in the first 2 hours, 1, 551 mg/dl in the next 10 hours and 254 ng/dl in the last 12 hours in orally administered patients and the mean CSA level of the peripheral blood was 746 ng/ml at 2 hours, 263 ng/ml at 12 hours and 119 ng/ml at 24 hours later. In intravenous administration, the mean CSA level of the lymph was 68 ng/ml, 58 ng/ml and 33 ng/ml and the mean CSA level of the peripheral blood was 452 ng/ml, 105 ng/ml and 88 ng/ml respectively. The mean CSA level of the lymph node was 3, 222 ng/g and the mean diffusion rate from the peripheral blood to the lymph node was 17.1. There was no difference between oral and intravenous administration. These results indicated that (1) there is a second pathway in which orally administered CSA is transported from small bowel to general circulation; via mesenteric lymph duct, thoracic duct and subclavic vein and (2) CSA is selectively uptaken by lymph node. CSA might suppress the activation of T cells in the lymph node and the lymph more effectively than in the peripheral blood.