Pharmacokinetics and pharmacodynamics of pravastatin in children with familial hypercholesterolemia

Autor: Pertti J. Neuvonen, Mikko Neuvonen, Marjatta Antikainen, Mia Hedman
Rok vydání: 2003
Předmět:
Male
Spectrometry
Mass
Electrospray Ionization
medicine.medical_specialty
Statin
Adolescent
medicine.drug_class
Cmax
Blood lipids
Familial hypercholesterolemia
030204 cardiovascular system & hematology
030226 pharmacology & pharmacy
Hyperlipoproteinemia Type II
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Pharmacokinetics
Internal medicine
polycyclic compounds
medicine
Humans
Pharmacology (medical)
Child
Chromatography
High Pressure Liquid
Triglycerides
Pravastatin
Pharmacology
Creatinine
business.industry
Anticholesteremic Agents
Cholesterol
HDL
nutritional and metabolic diseases
Cholesterol
LDL
medicine.disease
3. Good health
Endocrinology
chemistry
Area Under Curve
Pharmacodynamics
Female
lipids (amino acids
peptides
and proteins)
business
medicine.drug
Zdroj: Clinical Pharmacology & Therapeutics. 74:178-185
ISSN: 0009-9236
Popis: 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 (Cmax) of pravastatin was 15.7 ng/mL (range, 1.6-55.0 ng/mL), and the mean time to reach Cmax 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. Clinical Pharmacology & Therapeutics (2003) 74, 178–185; doi: 10.1016/S0009-9236(03)00153-X
Databáze: OpenAIRE
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