Bührer M, Frey F J, Frey B M
Zieglerspital Berne, Switzerland.
Br J Clin Pharmacol. 1991 Jan;31(1):111-3. doi: 10.1111/j.1365-2125.1991.tb03868.x.
The concentration-time curves of prednisolone in cerebrospinal fluid (CSF) and plasma were measured following an equimolar i.v. bolus dose of prednisolone phosphate (five patients) and prednisolone phthalate (four patients). Independent of the prodrug administered, the value of the AUC (0.360 min) in CSF was more than three times lower than the corresponding value in plasma. The AUCs of unbound prednisolone in plasma were higher after prednisolone phosphate, than after prednisolone phthalate (68.1 +/- 15.7 vs 19.0 +/- 5.2 micrograms ml-1 min, P less than 0.001). Similarly, the AUCs of prednisolone were higher in the CSF after prednisolone phosphate, than after prednisolone phthalate (17.6 +/- 2.8 vs 3.3 +/- 1.0 micrograms ml-1 min, P less than 0.0001). The results indicate that the concentrations of prednisolone in CSF are much lower than the unbound concentrations in plasma and that therapeutic inequivalence should be expected when the two prodrugs are given in equimolar doses.
在静脉注射等摩尔剂量的磷酸泼尼松龙（5例患者）和邻苯二甲酸泼尼松龙（4例患者）后，测定了脑脊液（CSF）和血浆中泼尼松龙的浓度-时间曲线。无论给予何种前药，脑脊液中AUC（0.360分钟）的值比血浆中相应值低三倍多。磷酸泼尼松龙给药后血浆中游离泼尼松龙的AUC高于邻苯二甲酸泼尼松龙给药后（68.1±15.7对19.0±5.2微克·毫升⁻¹·分钟，P＜0.001）。同样，磷酸泼尼松龙给药后脑脊液中泼尼松龙的AUC高于邻苯二甲酸泼尼松龙给药后（17.6±2.8对3.3±1.0微克·毫升⁻¹·分钟，P＜0.0001）。结果表明，脑脊液中泼尼松龙的浓度远低于血浆中游离浓度，并且当给予等摩尔剂量的两种前药时，应预期治疗等效性的差异。
