Drug-drug interactions between raltegravir and pravastatin in healthy volunteers.
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.
van Luin
Matthijs
M
Department of Clinical Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. m.vanluin@akf.umcn.nl
Colbers
Angela
A
van Ewijk-Beneken Kolmer
Eleonora W J
EW
Verweij-van Wissen
Corrien P W G M
CP
Schouwenberg
Bas
B
Hoitsma
Arjen
A
da Silva
Hugo G
HG
Burger
David M
DM
D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001774:Blood Chemical Analysis; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000068898:Raltegravir Potassium; D055815:Young Adult
D044966:Anti-Retroviral Agents; D000924:Anticholesteremic Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D017035:Pravastatin