Pharmacokinetics and pharmacodynamics of pravastatin in children with familial hypercholesterolemia.

BACKGROUND: Pravastatin is a widely used statin in adults, but its pharmacokinetics in children is not known. Our aim was to determine the single-dose pharmacokinetics and the lipid-lowering effect and safety of short-term administration of pravastatin in children.
METHODS: Twenty children (age range, 4.9-15.6 years) with heterozygous familial hypercholesterolemia ingested a single dose of 10 mg pravastatin. Plasma concentrations of pravastatin were measured for up to 10 hours. The patients then took 10 mg pravastatin orally once daily for 8 weeks. The concentration of serum lipids and safety laboratory parameters were measured before and after 8 weeks of treatment.
RESULTS: The mean peak plasma concentration (C(max)) of pravastatin was 15.7 ng/mL (range, 1.6-55.0 ng/mL), and the mean time to reach C(max) was 1.4 hours (range, 0.5-4 hours). The mean elimination half-life of pravastatin was 1.6 hours (range, 0.85-4.2 hours). The area under the plasma concentration-time curve of pravastatin ranged from 5.7 to 58.9 ng. h/mL (mean value, 26.6 ng. h/mL). By 8 weeks of treatment, the serum concentration of total cholesterol had decreased 18% (P <.0001); low-density lipoprotein cholesterol, 21% (P <.0001); and triglycerides, 18% (not significant, P =.18). The concentration of high-density lipoprotein cholesterol had increased 8% (not significant, P =.13). Few transient adverse events occurred. No increases in serum alanine aminotransferase, creatine kinase, or creatinine level were observed.
CONCLUSIONS: The pharmacokinetic and pharmacodynamic profile of pravastatin in children is similar to that reported for adults. In the short term, the daily dose of 10 mg pravastatin was well tolerated and moderately effective in decreasing the serum cholesterol concentration. However, further studies are needed on the long-term safety and efficacy of pravastatin in children.