IMPROVED DOSE LINEARITY OF CYCLOSPORINE PHARMACOKINETICS FROM A MICROEMULSION FORMULATION
IMPROVED DOSE LINEARITY OF CYCLOSPORINE PHARMACOKINETICS FROM A MICROEMULSION FORMULATION
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DOI：
10.1023/a:1018923912135
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发表时间：
1994-02-01
影响因子：
3.7
通讯作者：
KUTZ, K
中科院分区：
文献类型：
--
作者：
MUELLER, EA;KOVARIK, JM;KUTZ, K
在200至800 mg剂量范围内，将微乳制剂（Sandimmune Neoral）中环孢素的药代动力学剂量比例和相对生物利用度与市售制剂（Sandimmune）进行了比较。在一项有48名健康志愿者参与的开放随机研究中，单次口服给药为软明胶胶囊。全血环孢素浓度通过特异性单克隆放射免疫测定法测定。与Sandimmune相比，在所有研究剂量水平下，Sandimmune Neoral的环孢素吸收率（最大浓度）和全身利用度（曲线下面积）均更高。Sandimmune的曲线下面积以低于剂量比例的方式增加，而Sandimmune Neoral的曲线下面积与线性药代动力学一致。由于这种差异，无法进行相对生物利用度的总体评估。与Sandimmune相比，Sandimmune Neoral的环孢素相对生物利用度范围为174 - 239%，取决于剂量水平。以Sandimmune Neoral给药后，环孢素暴露的口服生物利用度和剂量线性改善，应有助于在临床环境中更准确地进行剂量滴定。
The pharmacokinetic dose proportionality and relative bioavailability of cyclosporine from a microemulsion formulation (Sandimmune Neoral) were compared to those of the commercial formulation (Sandimmune) over the dosage range 200 to 800 mg. Single oral administrations were given as soft gelatin capsules in an open randomized study with 48 healthy volunteers. Whole-blood cyclosporine concentrations were determined by a specific monoclonal radioimmunoassay. In comparison to Sandimmune, the absorption rate (maximum concentration) and systemic availability (area under the curve) of cyclosporine were greater for Sandimmune Neoral at all dose levels investigated. The area under the curve for Sandimmune increased in a less than proportional manner with respect to dose, whereas that for Sandimmune Neoral was consistent with linear pharmacokinetics. Because of this difference, no global assessment of relative bioavailability could be performed. The relative bioavailability of cyclosporine from Sandimmune Neoral ranged from 174 to 239% compared to Sandimmune, depending on the dose level. The improvements in oral bioavailability and dose linearity of cyclosporine exposure after administration as Sandimmune Neoral should facilitate more accurate dosage titration in the clinical setting.