Pharmacokinetics, safety, and tolerability of gadoversetamide injection (OptiMARK) in subjects with central nervous system or liver pathology and varying degrees of renal function

J Magn Reson Imaging. 1999 Feb;9(2):317-21. doi: 10.1002/(sici)1522-2586(199902)9:2<317::aid-jmri25>3.0.co;2-b.

Abstract

The pharmacokinetic parameters, safety, and tolerability of OptiMARK (gadoversetamide injection), a gadolinium-based magnetic resonance imaging (MRI) contrast agent, were evaluated in 163 subjects with either central nervous system (CNS) or liver pathology with and without renal insufficiency, for which a contrast-enhanced MRI was indicated. A multicenter, double-blind, randomized, placebo-controlled, parallel-group design was used in which subjects received 0.1, 0.3, or 0.5 mmol/kg of OptiMARK or placebo intravenously. Samples were analyzed for total gadolinium by inductively coupled plasma/mass spectrometry. Gadolinium pharmacokinetics were affected by renal impairment: area under the curve, half-life, and steady-state distribution volume significantly increased with declining renal function, while total body clearance decreased. In subjects with normal renal function, neither age, gender, nor liver versus CNS pathology altered gadolinium pharmacokinetics. No clinically significant changes from baseline were noted in vital signs, laboratory measures, electrocardiograms, or physical examinations. OptiMARK is safe and well-tolerated following a single intravenous injection in subjects with either liver or CNS pathology despite a prolonged elimination half-life in subjects with renal impairment.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Central Nervous System / pathology
  • Central Nervous System Diseases / diagnosis*
  • Contrast Media* / administration & dosage
  • Contrast Media* / pharmacokinetics
  • Double-Blind Method
  • Female
  • Gadolinium / adverse effects
  • Gadolinium / pharmacokinetics
  • Humans
  • Injections, Intravenous
  • Liver / pathology
  • Liver Diseases / diagnosis*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Organometallic Compounds* / adverse effects
  • Organometallic Compounds* / pharmacokinetics
  • Renal Insufficiency / physiopathology*
  • Safety

Substances

  • Contrast Media
  • Organometallic Compounds
  • Gadolinium
  • gadoversetamide