Management of drug-to-drug interactions between cyclosporine A and the protease-inhibitor lopinavir/ritonavir in liver-transplanted HIV-infected patients
✍ Scribed by Martin Vogel; Esther Voigt; Hans-Christoph Michaelis; Thomas Sudhop; Martin Wolff; Andreas Türler; Tilman Sauerbruch; Jürgen Kurt Rockstroh; Ulrich Spengler
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 147 KB
- Volume
- 10
- Category
- Article
- ISSN
- 1527-6465
- DOI
- 10.1002/lt.20165
No coin nor oath required. For personal study only.
✦ Synopsis
Highly active antiretroviral therapy (HAART) has improved the life expectancy of HIV-infected patients, allowing orthotopic liver transplantation as a reasonable treatment option for selected patients with terminal liver disease. Both non-nucleoside reverse transcriptase inhibitors and protease inhibitors, key elements of HAART, give rise to substantial drug-to-drug interactions with immunosuppressive drugs such as tacrolimus and cyclosporine A. After studying 12-hour pharmacokinetic profiles in 3 HIV-positive patients after liver transplantation, we describe how dosing of cyclosporine A can be adjusted to maintain effective immunosuppressive drug levels on a daily dosing schedule when ritonavir-boosted indinavir or lopinavir-based antiretroviral therapy is given. To avoid toxic drug levels, we used an orally available cyclosporine A formulation prepared from the commercial available intravenous solution, which enabled dose adjustments in 1-mg increments. Under ritonavir-boosted HAART, cyclosporine A levels showed markedly altered absorption/elimination characteristics with more or less constant blood-levels throughout the dosing interval and prolonged elimination half-lives up to 38 hours. To obtain equivalent areas under the curve of cyclosporine A, daily doses were reduced to 5 -20% of the individual standard doses given before initiation of ritonavir-boosted HAART. Because of the flat absorption/elimination profiles under ritonavir-boosted HAART cyclosporine A, dosing could be reliably monitored long term by measuring cyclosporine A trough-levels. (Liver