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

• Published in: Antiviral therapy Vol. 12; no. 7; pp. 1127 - 1132
• Main Authors: VAN DER LEE, Manon, SANKATSING, Raaj, DE GROOT, Eric, KOOPMANS, Peter, STROES, Erik, REISS, Peter, BURGER, David, SCHIPPERS, Emile, VOGEL, Martin, FÄTKENHEUER, Gerd, VAN DER VEN, Andre, KROON, Frank, ROCKSTROH, Jürgen, WYEN, Christoph, BÄUMER, Anselm
• Format: Journal Article
• Language: English
• Published: London International Medical Press 01.01.2007
• Subjects: Adolescent; Adult; Aged; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - pharmacokinetics; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Drug Therapy, Combination; Fluorobenzenes - administration & dosage; Fluorobenzenes - pharmacokinetics; Fluorobenzenes - therapeutic use; HIV Infections - drug therapy; HIV Infections - virology; Human viral diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypercholesterolemia - chemically induced; Hypercholesterolemia - drug therapy; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Lopinavir; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Pilot Projects; Pyrimidines - administration & dosage; Pyrimidines - pharmacokinetics; Pyrimidines - therapeutic use; Pyrimidinones - administration & dosage; Pyrimidinones - pharmacokinetics; Pyrimidinones - therapeutic use; Ritonavir - administration & dosage; Ritonavir - pharmacokinetics; Ritonavir - therapeutic use; Rosuvastatin Calcium; Sulfonamides - administration & dosage; Sulfonamides - pharmacokinetics; Sulfonamides - therapeutic use; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Pharmacokinetic pharmacodynamic relationship; Antiretroviral agent; Ritonavir; Lipids; Rosuvastatin; Antiviral; Hyperlipemia; Drug interaction; Dyslipemia; Human; Immunopathology; Drug combination; Enzyme; Lopinavir; Enzyme inhibitor; Metabolic diseases; AIDS; Statin derivative; Immune deficiency; Infection; Peptidases; Viral disease; Hydrolases; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases; Pharmacokinetics; Protease inhibitor; Antilipemic agent
• ISSN: 1359-6535; 2040-2058
• DOI: 10.1177/135965350701200711

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. 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. 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. 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.