Pharmacokinetics of (+)-, (-)- and (+/-)-verapamil after intravenous administration

Br J Clin Pharmacol. 1984 Apr;17(4):453-8. doi: 10.1111/j.1365-2125.1984.tb02371.x.


The pharmacokinetics of (+)-, (-)-, and (+/-)-verapamil were studied in five healthy volunteers following i.v. administration of the drugs. Pronounced differences of the various pharmacokinetic parameters were observed between the (-)- and (+)-isomers. The values for CL, V, Vz, and Vss of the (-)-isomer were substantially higher as compared to the (+)-isomer, whereas terminal t 1/ 2Z was nearly identical for both isomers. No dose dependency of the pharmacokinetics could be observed in two subjects who received 5, 7.5 and 10 mg of (-)- and 5, 25 and 50 mg of (+)-verapamil. Protein binding for the two isomers was also different. The fu of (-)- (0.11) was almost twice as much as that of (+)-verapamil (0.064). Pharmacokinetic parameters of (+/-)-verapamil, which was administered to three subjects who had received (+)- and (-)-verapamil, were very similar to the averaged values of the isomers given separately. Due to the higher CL of (-)-verapamil the extraction ratio of the (-)-isomer is substantially higher. Thus, it can be anticipated that following oral administration of racemic verapamil bioavailability of (-)-verapamil will be substantially less. Since the (-)-isomer is more potent than the (+)-isomer, the present findings could explain the reported differences in the concentration-effect relationship after i.v. and oral administration of racemic verapamil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biological Availability
  • Blood Proteins / metabolism
  • Gas Chromatography-Mass Spectrometry
  • Half-Life
  • Humans
  • Infusions, Parenteral
  • Kinetics
  • Male
  • Protein Binding
  • Stereoisomerism
  • Verapamil / administration & dosage
  • Verapamil / metabolism*


  • Blood Proteins
  • Verapamil