Relative bioavailability of cyclosporin from conventional and microemulsion formulations in heart-lung transplant candidates with cystic fibrosis

✍ Scribed by K. K. C. Tan; J. A. Uttridge; A. K. Trull; J. Wallwork

• Publisher: Springer
• Year: 1995
• Tongue: English
• Weight: 492 KB
• Volume: 48-48
• Category: Article
• ISSN: 0031-6970
• DOI: 10.1007/bf00198313

✦ Synopsis

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. Cm~x 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 C .... 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 K. K.C. Tan ([])1. j. A. Uttridge 2