BACKGROUND: To evaluate the potential drug-drug interaction between raltegravir and pravastatin. METHODS: This was an open-label, randomized, 3-period, cross-over, single-centre trial in 24 healthy volunteers. Subjects received the following treatments: pravastatin 40 mg every day for 4 days, raltegravir 400 mg twice a day for 4 days, and pravastatin 40 mg every day + raltegravir 400 mg twice a day for 4 days. The treatments were separated by washout periods of 10 days. On day 4 of each treatment period, blood samples for pharmacokinetics were collected throughout a 24-hour period. RESULTS:Geometric mean ratios (90% confidence interval) for pravastatin + raltegravir versus pravastatin alone were 0.96 (0.83 to 1.11) for AUC0-24 and 1.04 (0.85 to 1.26) for Cmax. The mean low-density lipoprotein cholesterol decrease after 4 days of pravastatin was 0.42 mmol/L both in the presence and the absence of raltegravir. The geometric mean ratio (90% confidence interval) AUC0-12, Cmax, and C12 for raltegravir + pravastatin versus raltegravir alone were 1.13 (0.77 to 1.65), 1.31 (0.81 to 2.13), and 0.59 (0.39 to 0.88), respectively. CONCLUSIONS:Raltegravir did not influence the pharmacokinetics or the short-term lipid-lowering effects of pravastatin, whereas pravastatin increased the Cmax but decreased the C12 of raltegravir. The effects of pravastatin on raltegravir pharmacokinetics are not likely to be clinically relevant.
RCT Entities:
BACKGROUND: To evaluate the potential drug-drug interaction between raltegravir and pravastatin. METHODS: This was an open-label, randomized, 3-period, cross-over, single-centre trial in 24 healthy volunteers. Subjects received the following treatments: pravastatin 40 mg every day for 4 days, raltegravir 400 mg twice a day for 4 days, and pravastatin 40 mg every day + raltegravir 400 mg twice a day for 4 days. The treatments were separated by washout periods of 10 days. On day 4 of each treatment period, blood samples for pharmacokinetics were collected throughout a 24-hour period. RESULTS: Geometric mean ratios (90% confidence interval) for pravastatin + raltegravir versus pravastatin alone were 0.96 (0.83 to 1.11) for AUC0-24 and 1.04 (0.85 to 1.26) for Cmax. The mean low-density lipoprotein cholesterol decrease after 4 days of pravastatin was 0.42 mmol/L both in the presence and the absence of raltegravir. The geometric mean ratio (90% confidence interval) AUC0-12, Cmax, and C12 for raltegravir + pravastatin versus raltegravir alone were 1.13 (0.77 to 1.65), 1.31 (0.81 to 2.13), and 0.59 (0.39 to 0.88), respectively. CONCLUSIONS:Raltegravir did not influence the pharmacokinetics or the short-term lipid-lowering effects of pravastatin, whereas pravastatin increased the Cmax but decreased the C12 of raltegravir. The effects of pravastatin on raltegravir pharmacokinetics are not likely to be clinically relevant.