Management of drug‐to‐drug interactions between cyclosporine A and the protease‐inhibitor lopinavir/ritonavir in liver‐transplanted HIV‐infected patients.
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Study Design
The pharmacokinetic interaction between lopinavir/ritonavir and cyclosporine was investigated in 3 HIV+ patients after liver transplant; cyclosporine pharmacokinetics were available in 2/3 patients prior to starting lopinavir/ritnavir and in all three patients 3-6 weeks after starting lopinavir/ritonavir.
Study Results
Prior to lopinavir/ritonavir, cyclosporine pharmacokinetic showed typical absorption and elimination characteristics (Tmax ~1 h, half-life 4-6 h) and were comparable to those obtained in HIV- subjects. Following the addition of LPV/RTV (400/100 mg twice daily), a marked alteration in the cyclosporine pharmacokinetic plasma profile was observed - absorption/elimination curves were flattened and there was little variation in concentrations over the 12 h profile. Tmax was delayed, Cmax reduced and half-life prolonged up to 38 h. To maintain target cyclosporine trough concentrations (75-125 ng/ml), dose reductions to 5-20% of the original dose were required.
Study Conclusions
Coadministration may result in increased plasma concentrations of cyclosporine. Therapeutic concentration monitoring is recommended for immunosuppressants when coadministered with boosted protease inhibitors.
References
Vogel M, Voight E, Michaelis HC, Sudhop T, Wolff M, Turler A, Spengler U. Management of drug‐to‐drug interactions between cyclosporine a and the protease‐inhibitor lopinavir/ritonavir in liver‐transplanted hiv‐infected patients. Liver Transplantation. 2004; 7: 939-944.
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