Absolute and relative bioavailability of the HMG-CoA reductase inhibitor cerivastatin

Int J Clin Pharmacol Ther. 1997 Jun;35(6):255-60.

Abstract

To determine the absolute bioavailability of the HMG-CoA reductase inhibitor cerivastatin, 12 healthy young male volunteers received single doses of either 100 micrograms as a 1-minute bolus infusion or 200 micrograms orally as tablets in a controlled, randomized crossover study. In addition, 8 of the 12 subjects participated in a third treatment period in which 200 micrograms cerivastatin were administered as an oral solution as reference for determining the relative bioavailability of the tablet drug formulation. Plasma samples were analyzed for cerivastatin by a specific HPLC assay with fluorescence detection after post-column irradiation of the eluate, with a limit of quantification of 0.1 microgram/l. Following all treatments, cerivastatin was well tolerated and no clinically relevant adverse events or changes in laboratory parameters were observed. Vital signs and ECG remained unchanged. Plasma concentration/time profiles of cerivastatin following intravenous bolus could be described by a 2-compartment model with a distribution half-life of 3-5 min and an elimination half-life of 1.5-2.4 h. For the 2 oral administrations a 1-compartmental pharmacokinetic model with a first-order absorption process was best to describe the plasma concentration/time data. Based on the AUCnorm values of the 7 subjects, valid for complete pharmacokinetic evaluation, the absolute bioavailability of tablet and oral solution was 60.0 and 59.6% (90% confidence intervals 53-68%), respectively. The relative bioavailability of tablet compared with solution was 100.7% (90% confidence interval 89-114%), with tablet and oral solution showing nearly identical in vivo absorption characteristics and almost superimposable plasma concentration/time curves. The tablet formulation, therefore, can be regarded as an optimal oral formulation with respect to galenic aspects.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Area Under Curve
  • Biological Availability
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Electrocardiography / drug effects
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / blood
  • Enzyme Inhibitors / pharmacokinetics*
  • Half-Life
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Injections, Intravenous
  • Male
  • Pilot Projects
  • Pyridines / administration & dosage
  • Pyridines / adverse effects
  • Pyridines / blood
  • Pyridines / pharmacokinetics*
  • Spectrometry, Fluorescence
  • Tablets

Substances

  • Enzyme Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyridines
  • Tablets
  • cerivastatin