Kees Brinkman, MD, PhD; Frans Huysmans, MD, PhD; David M. Burger, PharmD, PhD
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Brinkman K, Huysmans F, Burger DM. Pharmacokinetic Interaction between Saquinavir and Cyclosporine. Ann Intern Med. 1998;129:914-915. doi: 10.7326/0003-4819-129-11_Part_1-199812010-00022
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Published: Ann Intern Med. 1998;129(11_Part_1):914-915.
TO THE EDITOR:
An HIV-positive kidney transplant recipient who was receiving cyclosporine and prednisone started zidovudine and lamivudine therapy shortly after kidney function had stabilized. When protease inhibitors became available, saquinavir was added; levels of both drugs were monitored.
Without saquinavir, the cyclosporine trough levels in this patient were stable at a dosage of 150 mg twice daily (150 to 200 µg/L). Within 3 days after saquinavir therapy began at a dosage of 1200 mg three times daily, the patient reported fatigue, headache, and gastrointestinal discomfort and the trough level of cyclosporine tripled to 580 µg/L. After cyclosporine and saquinavir dosages were decreased to 75 mg twice daily and 600 mg three times daily, respectively, the symptoms subsided. Time curve analysis showed that an area under the concentration-time curve (AUC0−12) seen with 75 mg of cyclosporine during treatment with saquinavir was 90% of the AUC0−12 seen with 150 mg of cyclosporine alone (Figure 1, top). Meanwhile, saquinavir showed an AUC0−12 4.3 times higher than the average value of five control patients who were receiving an identical saquinavir dosage of 600 mg twice daily without cyclosporine (Figure 1, bottom) and 11.1 times higher than the AUC0−12 reported in the literature (0.47 h per mg/L) .
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