Tan K K, Trull A K, Uttridge J A, Wallwork J
Clinical and Biochemical Pharmacology Unit, Papworth Hospital, Cambridge, UK.
Eur J Clin Pharmacol. 1995;48(3-4):285-9. doi: 10.1007/BF00198313.
Patients with cystic fibrosis absorb cyclosporin poorly and erratically. We have compared the relative bioavailability of cyclosporin from conventional and microemulsion formulations in 5 adult heart-lung transplant candidates with cystic fibrosis. Relative bioavailability was compared at two dose levels (200 mg and 800 mg). A randomized 4-period cross-over study was performed with at least a 7 day washout period between each single dose pharmacokinetic study. Blood cyclosporin concentrations were measured by a selective monoclonal antibody-based radioimmunoassay. The bioavailability of cyclosporin from the microemulsion formulation was 1.84 (95% C.I. 1.05 to 3.22; P = 0.04) and 2.09 (95% C.I. 0.95 to 4.61; P = 0.06) times higher compared with the conventional formulation at 200 mg and 800 mg respectively. Cmax following the microemulsion formulation was 3.38 (C.I. 1.14 to 10.59; P = 0.04) and 2.77 (C.I. 1.48 to 5.19; P = 0.01) times higher compared with the conventional formulation at 200 mg and 800 mg respectively. The higher Cmax following the microemulsion formulation was accompanied by shorter tmax. An enhancement of cyclosporin absorption with the microemulsion formulation was demonstrated in each patient for at least one dose level. We conclude that rate and extent of cyclosporin absorption from the microemulsion formulation is greater compared with the conventional formulation in patients with cystic fibrosis. The potential therapeutic and economic benefits of the microemulsion formulation should be evaluated in cystic fibrosis patients following heart-lung transplantation.
患有囊性纤维化的患者对环孢素的吸收较差且不稳定。我们比较了5名成年囊性纤维化心肺移植候选者使用常规制剂和微乳剂制剂后环孢素的相对生物利用度。在两个剂量水平（200毫克和800毫克）下比较了相对生物利用度。进行了一项随机4期交叉研究，每次单剂量药代动力学研究之间至少有7天的洗脱期。通过基于选择性单克隆抗体的放射免疫测定法测量血中环孢素浓度。在200毫克和800毫克剂量下，微乳剂制剂中环孢素的生物利用度分别比常规制剂高1.84倍（95%置信区间1.05至3.22；P = 0.04）和2.09倍（95%置信区间0.95至4.61；P = 0.06）。微乳剂制剂后的Cmax分别比200毫克和800毫克剂量下的常规制剂高3.38倍（置信区间1.14至10.59；P = 0.04）和2.77倍（置信区间1.48至5.19；P = 0.01）。微乳剂制剂后的较高Cmax伴随着较短的tmax。在每个患者的至少一个剂量水平上都证明了微乳剂制剂可增强环孢素的吸收。我们得出结论，在患有囊性纤维化的患者中，与常规制剂相比，微乳剂制剂中环孢素的吸收速率和程度更大。微乳剂制剂的潜在治疗和经济效益应在心肺移植后的囊性纤维化患者中进行评估。
