Pharmacokinetics and pharmacodynamics of combined use of lopinavir/ritonavir and rosuvastatin in HIV-infected patients.

Pharmacokinetics and pharmacodynamics of combined use of lopinavir/ritonavir and rosuvastatin in HIV-infected patients. Research Abstract Details 

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Pharmacokinetics and pharmacodynamics of combined use of lopinavir/ritonavir and rosuvastatin in HIV-infected patients. Abstract Text:

Manon van der Lee,Raaj Sankatsing,Emile Schippers,Martin Vogel,Gerd ,Andre van der Ven,Frank Kroon, Rockstroh,Christoph Wyen,Anselm ,Eric de Groot,Peter Koopmans,Erik Stroes,Peter Reiss,David Burger,Manon van der Lee,Raaj Sankatsing,Emile Schippers,Martin Vogel,Gerd ,Andre van der Ven,Frank Kroon, Rockstroh,Christoph Wyen,Anselm ,Eric de Groot,Peter Koopmans,Erik Stroes,Peter Reiss,David Burger,

BACKGROUND: Lopinavir/ritonavir-containing antiretroviral therapy can cause hyperlipidaemia. However, most statins are contraindicated due to drug-drug interactions. Rosuvastatin undergoes minimal metabolism by CYP450, so no CYP450-based interaction with lopinavir/ritonavir is expected. This study explored the lipid-lowering effect of rosuvastatin and assessed the effect of lopinavir/ritonavir on the pharmacokinetics of rosuvastatin and vice versa. METHODS: HIV-infected patients on lopinavir/ritonavir (viral load < 400 copies/ml) with total cholesterol (TC) > 6.2 mmol/l were treated with rosuvastatin for 12 weeks, starting on 10 mg once daily. If fasting target values (TC < 5.0 mmol/l, high-density lipoprotein-cholesterol > 1.0 mmol/l, low-density lipoprotein-cholesterol [LDL-c] < 2.6 mmol/l and triglycerides < 2.0 mmol/l) were not reached, rosuvastatin was escalated to 20 mg or 40 mg at week 4 and 8, respectively. Plasma lopinavir/ritonavir trough levels (C(min)) were determined at week 0, 4, 8 and 12 and rosuvastatin C(min), at week 4, 8 and 12. RESULTS: Twenty-two patients completed the study. Mean reductions in TC and LDL-c from baseline to week 4 (on rosuvastatin 10 mg once a day) were 27.6% and 31.8%, respectively. Lopinavir/ritonavir concentrations were not influenced by rosuvastatin (P = 0.44 and 0.26, repeated-measures analysis). Median (interquartile range) rosuvastatin C(min) for 10 mg, 20 mg and 40 mg once daily were 0.97 (0.70-1.5), 2.5 (1.3-3.3) and 5.5 (3.3-8.8) ng/ml, respectively. CONCLUSIONS: Rosuvastatin appeared to be an effective statin in hyperlipidaemic HIV-infected patients. Lopinavir/ritonavir levels were not affected by rosuvastatin, but rosuvastatin levels unexpectedly appeared to be increased 1.6-fold compared with data from healthy volunteers. Until safety and efficacy have been confirmed in larger studies, the combination of rosuvastatin and lopinavir/ritonavir should be used with caution.

Pharmacokinetics and pharmacodynamics of combined use of lopinavir/ritonavir and rosuvastatin in HIV-infected patients. Publishing Authors By Initials

M van der Lee,R Sankatsing,E Schippers,M Vogel,G ,A van der Ven,F Kroon,J Rockstroh,C Wyen,A ,E de Groot,P Koopmans,E Stroes,P Reiss,D Burger,M van der Lee,R Sankatsing,E Schippers,M Vogel,G ,A van der Ven,F Kroon,J Rockstroh,C Wyen,A ,E de Groot,P Koopmans,E Stroes,P Reiss,D Burger,

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Pharmacokinetics and pharmacodynamics of combined use of lopinavir/ritonavir and rosuvastatin in HIV-infected patients. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Antiviral therapy

VOLUME: 12

Page Numbers: 1127-32

Journal Abbreviation: Antivir. Ther. (Lond.)

ISSN: 1359-6535

DAY: 16

MONTH: 11

YEAR: 2007

Pharmacokinetics and pharmacodynamics of combined use of lopinavir/ritonavir and rosuvastatin in HIV-infected patients. Information

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LANGUAGE: eng

NlmUniqueID: 9815705

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AFFILIATION: Department of Clinical Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. m.vanderlee@akf.umcn.nl

Country: England

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MEDLINETA: Antivir Ther

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