Studies on concentration-time profiles of nimodipine enantiomers following intravenous and oral administration of nimodipine in patients with subarachnoid hemorrhage

After i.v. and oral administration of nimodipine the concentration-time profiles of the drug and its enantiomers were studied ill seven patients with subarachnoid hemorrhage, Concentrations of nimodipine, (+)-(R)-, and (-)-(S)-nimodipine were analyzed using a new stereoselective high-performance liquid chromatographic method. During the first 3 h after oral administration the concentrations of (+)-(R)- and (-)-(S)-nimodipine were significantly different, the (-)-(S)-enantiomer being found in much lesser concentrations compared to the (+)-(R)-enantiomer. The results indicate that if uptake from the gastrointestinal system is equal for the two enantiomers, then (-)-(S)-nimodipine is metabolized at a much faster rate compared to (+)-(R)-nimodipine after oral administration of the drug in patients with subarachnoid bleeding. After i.v, administration; no significant differences between the concentrations of the (-)-(S) and the (+)-(R) isomers were demonstrated. Chirality 12:660-664, 2000. (C) 2000 Wiley-Liss, Inc.