ritonavir and pitavastatin

Dyslipidemia as a risk factor of cardiovascular disease is common especially in HIV-infected patients who are using protease inhibitors (PIs) including atazanavir. Pitavastatin has less drug-drug interactions and demonstrable efficacy in decreasing lipid levels in non HIV-infected individuals.. This study was a randomized, double-blind, crossover study comparing the safety and efficacy of pitavastatin vs placebo in HIV-infected patients with dyslipidemia and receiving atazanavir/ritonavir (ATV/r). Patients were randomized to receive either placebo or pitavastatin for 12 weeks. The follow-up visits were every 4 weeks until the end of the study.. A total of 12 HIV-infected patients were enrolled to each study group. Of all, 14 (58%) patients were men and mean (standard deviation, SD) age was 48.1 (1.8) years. At 12 weeks of treatment with pitavastatin compared to placebo; mean [95% confidence interval (CI)] total cholesterol (TC) was 207 (187.3, 226.8) mg/dL vs 246.3 (226.5, 266) mg/dL (p <0.001); mean (95% CI) triglyceride (TG) was 351.3 (193.2, 509.4) mg/dL vs 279.1 (121, 437.2) mg/dL (p = 0.269); mean (95% CI) high density lipoprotein (HDL) was 45.3 (40.4, 50.2) mg/dL vs 44.2 (39.3, 49.1) mg/dL (p = 0.354); and mean (95% CI) low density lipoprotein (LDL) was 113.2 (100.4, 126) mg/dL vs 145.6 (132.8, 158.4) mg/dL (p <0.001). Mean liver enzyme and median creatine phosphokinase levels were not statistically significant between patients receiving placebo and pitavastatin.. Pitavastatin decreases TC and LDL level at 12 weeks significantly and shows indifferent in hepatotoxicity and creatine phosphokinase levels compared to those of placebo. Thus, pitavastatin can be a good option of lipid-lowering agent in HIV-infected patients who are receiving ATV/r.. ClinicalTrials.gov NCT02442700.

Topics: Adult; Atazanavir Sulfate; Cholesterol; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Dyslipidemias; Female; Follow-Up Studies; HIV Infections; HIV Protease Inhibitors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Lipoproteins, LDL; Male; Middle Aged; Quinolines; Ritonavir; Treatment Outcome; Triglycerides

The treatment of hyperlipidaemia in human immunodeficiency virus (HIV)-infected patients has become increasingly important. However, treatment options are limited because of the drug-drug interaction between certain statins and HIV medications metabolized by cytochrome P450 (CYP) enzymes.. The primary objective was to investigate the steady-state pharmacokinetics of pitavastatin when co-administered with darunavir/ritonavir. The secondary objective was to investigate the steady-state pharmacokinetics of both darunavir and ritonavir when co-administered with pitavastatin.. This was a single-centre, open-label, multi-dose, fixed-sequence study in HIV seronegative healthy volunteers. Pitavastatin 4 mg was administered once daily on days 1-5 and on days 12-16, and darunavir 800 mg/ritonavir 100 mg once daily on days 6-16. Pharmacokinetic blood sampling was performed on days 5, 11 and 16. No significant interaction was concluded if the 90 % confidence intervals (CIs) of the geometric mean ratios (GMRs) for total exposure [i.e. the area under the plasma concentration-time curve over a dosing interval at steady state (AUC(0-τ))] and for peak exposure [i.e. the maximum plasma concentration (C(max))] of the two treatments were within the 80-125 % range.. Twenty-eight subjects (mean age 30.5 years) were enrolled, and pharmacokinetic data were available for 27 subjects. For pitavastatin, the GMRs and 90 % CIs for the AUC(0-τ) and C(max) ratios with co-administration were 0.74 (0.69-0.80) and 0.96 (0.84-1.09), respectively. For both darunavir and ritonavir, the 90 % CIs for the AUC(0-τ) and C max ratios were within 80-125 % with pitavastatin co-administration. No significant safety issues were reported.. Darunavir/ritonavir decreased total exposure to pitavastatin by 26 %, while peak exposures were similar. Pitavastatin did not influence the pharmacokinetics of darunavir or ritonavir. There is limited interaction between pitavastatin and darunavir/ritonavir.

Topics: Administration, Oral; Adolescent; Adult; Darunavir; Female; Healthy Volunteers; Humans; Male; Middle Aged; Quinolines; Ritonavir; Sulfonamides; Young Adult

The drug-drug interactions between pitavastatin and darunavir/ritonavir (DRV/r) as well as pitavastatin and efavirenz (EFV) were examined in an open-label, parallel-arm, pharmacokinetic (PK) study in HIV-uninfected healthy volunteers.. Subjects received a pitavastatin dose of 2 mg for 4 days, followed by either EFV 600 mg (n = 14) or DRV/r 800/100 mg (n = 14) daily for 10 days, and pitavastatin 2 mg coadministered with EFV 600 mg or DRV/r 800/100 mg for 4 days. Full PK profiles were determined for pitavastatin and its lactone metabolite on days 4 and 18 and for EFV or DRV on days 14 and 18.. In the EFV arm, the geometric mean area under the concentration time curve (AUC0-τ) and Cmax of pitavastatin were 85.3 ng·h·mL and 15.6 ng/mL, respectively, when given alone, versus 76 ng·h·mL and 18.8 ng/mL when coadministered with EFV. The geometric mean ratio for pitavastatin with EFV versus alone was 0.89 [90% confidence interval (CI): 0.73 to 1.09] for AUC0-τ and 1.20 (90% CI: 0.79 to 1.83) for Cmax. In the DRV/r arm, AUC0-τ and Cmax were 62.8 ng·h·mL and 24.0 ng/mL, respectively, when pitavastatin was administered alone, versus 56.9 ng·h·mL and 23.2 ng/mL when coadministered with DRV/r. The geometric mean ratio for pitavastatin with DRV/r versus alone was 0.91 (90% CI: 0.78 to 1.06) for AUC0-τ and 0.93 (90% CI: 0.72 to 1.19) for Cmax.. There were no significant PK interactions between pitavastatin and EFV or DRV/r. No significant safety issues or lipid changes were noted.

Topics: Adolescent; Adult; Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Darunavir; Drug Interactions; Female; HIV Protease Inhibitors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Quinolines; Ritonavir; Sulfonamides; Young Adult

Pitavastatin, a statin recently approved in the United States, has a potential benefit of reduced risk of cytochrome P450 (CYP)-mediated drug-drug interaction due to minimal metabolism by the CYP system. The primary objective was to investigate pharmacokinetic (PK) effects of lopinavir/ritonavir 400 mg/100 mg twice daily on pitavastatin 4 mg when coadministered.. This was an open-label one-arm study.. Pitavastatin 4 mg was administered once daily (days 1-5 and days 20-24). Lopinavir/ritonavir 400 mg/100 mg was administered twice daily (days 9-24). Plasma samples for PK assessments were collected on days 5, 19, and 24. Plasma concentrations of analytes were determined by liquid chromatography with tandem mass spectrometric detection methods.. PK data were available for 23 of 24 subjects enrolled. For pitavastatin, area under the concentration time curve (AUC0-τ) and maximum concentration (C(max)) were 136.8 ± 52.9 ng·h(-1)·mL(-1) and 58.6 ± 30.4 ng/mL, respectively, when given alone, versus 113.9 ± 53.8 ng·h(-1)·mL(-1) and 58.2 ± 32.7 ng/mL when combined with lopinavir/ritonavir. The geometric mean ratio for AUC(0-τ) for pitavastatin with lopinavir/ritonavir versus pitavastatin alone was 80.0 (90% confidence interval: 73.4 to 87.3) and C(max) was 96.1 (90% confidence interval: 83.6 to 110.4). Median T(max) of pitavastatin was approximately 0.5 hours for both treatments. The PK effect of pitavastatin on lopinavir/ritonavir was minimal. No significant safety issues were reported.. The effect on exposures when pitavastatin and lopinavir/ritonavir are coadministered was minimal. Concomitant use of pitavastatin and lopinavir/ritonavir was safe and well tolerated in healthy adult volunteers.

Topics: Adolescent; Adult; Antiviral Agents; Drug Interactions; Female; Human Experimentation; Humans; Hydroxymethylglutaryl CoA Reductases; Lopinavir; Male; Middle Aged; Quinolines; Ritonavir; United States; Young Adult