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Early-phase pharmacokinetics of enteral and parenteral nimodipine in patients with acute subarachnoid haemorrhage – a pilot study

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

The pharmacokinetics of nimodipine following enteral administration in the early phase after subarachnoid haemorrhage (SAH) has not been described. If a sufficient absorption could be achieved with enterally administered nimodipine, this would be more feasible dosage form and result in a significant reduction in pharmaceutical costs given that the parenteral formulation of nimodipine currently used is tenfold more expensive than the enteral formulation.

Methods

This was a pilot study in which 17 patients with aneurysmal SAH were randomly assigned to receive nimodipine within 24 h after initial bleeding either as an 60 mg tablet/suspension at 4-h intervals, or as a continuous intravenous infusion of 2 mg/h. Serum nimodipine concentrations were measured during the 4 h following the first dose, and at 24 and 72 h on a validated gas chromatography mass spectrometer (GC-MS).

Results

Nimodipine AUC values (expressed in μg min/ml) were lower in the eight SAH patients receiving enteral nimodipine [AUC0–4 range: 0.13–5.4 (median: 0.32); AUC24–28 range: 0.16–6.1 (0.71); AUC72–76 range: 0.47–20.6 (1.9)] than in the nine patients receiving a continuous intravenous infusion of nimodipine [AUC0–4 range: 2.4–4.9 (3.4), p = 0.059; AUC24–28 range: 4.7–10.3 (7.3), p = 0.001; AUC72–76 range: 3.4–8.6 (6.9), p = 0.001]. In three of five good-grade SAH patients receiving nimodipine tablets the AUC values were comparable to those of the intravenous administration, but in two good-grade patients with tablets and in all three poor-grade (Hunt&Hess, grade IV) SAH patients receiving the suspension, the rate and extent of nimodipine absorption was negligible.

Conclusion

This pilot study indicates that the rate and extent of nimopidine absorption following enteral administration in some acute SAH patients could be negligible, and this may particularly be the case in patients with a decreased level of consciousness.

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Acknowledgements

This study was financially supported by an EVO grant from Kuopio University Hospital. The persons contributing to this study do not have any specific conflict of interest. The technical help of laboratory assistant Anne Riekkinen, MSc (Pharmacology), Kirsi Kontra and Toivo Naaranlahti PhD (Pharmacology) is appreciated.

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Authors and Affiliations

  1. Department of Neurosurgery, Kuopio University Hospital, P.O. Box 1777, 70211, Kuopio, Finland

    Ville Soppi, Timo Koivisto & Jaakko Rinne

  2. Department of Anaesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland

    Hannu Kokki

  3. Department of Pharmacology and Toxicology, University of Kuopio, Kuopio, Finland

    Hannu Kokki & Sanna Lehtola

  4. Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland

    Marko Lehtonen

  5. Department of Pharmacy, Kuopio University Hospital, Kuopio, Finland

    Minna Helin-Tanninen

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  1. Ville Soppi
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  2. Hannu Kokki
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  5. Minna Helin-Tanninen
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  7. Jaakko Rinne
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Correspondence to Ville Soppi.

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Soppi, V., Kokki, H., Koivisto, T. et al. Early-phase pharmacokinetics of enteral and parenteral nimodipine in patients with acute subarachnoid haemorrhage – a pilot study. Eur J Clin Pharmacol 63, 355–361 (2007). https://doi.org/10.1007/s00228-007-0267-7

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  • DOI: https://doi.org/10.1007/s00228-007-0267-7

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