J Neurol Surg A Cent Eur Neurosurg 2012; 73(03): 153-159
DOI: 10.1055/s-0032-1313724
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Prophylactic Intravenous Nimodipine Treatment in Skull Base Surgery: Pharmacokinetic Aspects[*]

C. Scheller
1   University of Halle-Wittenberg, Department of Neurosurgery, Halle (Saale), Germany
,
A.-S. Vogel
1   University of Halle-Wittenberg, Department of Neurosurgery, Halle (Saale), Germany
,
S. Simmermacher
1   University of Halle-Wittenberg, Department of Neurosurgery, Halle (Saale), Germany
,
J. C. Rachinger
1   University of Halle-Wittenberg, Department of Neurosurgery, Halle (Saale), Germany
,
J. Prell
1   University of Halle-Wittenberg, Department of Neurosurgery, Halle (Saale), Germany
,
C. Strauss
1   University of Halle-Wittenberg, Department of Neurosurgery, Halle (Saale), Germany
,
M. Reinsch
1   University of Halle-Wittenberg, Department of Neurosurgery, Halle (Saale), Germany
,
U. Kunter
2   Analytisches Zentrum Biopharm GmbH Berlin, Bioanalytics, Berlin, Germany
,
A. Wienke
3   University of Halle-Wittenberg, Institue for Medical Epidemilogy, Halle, Germany
,
J. Neumann
5   Institute of Pharmacology and Toxicology, University of Halle-Wittenberg, Halle, Germany
,
K. Scheller
4   University Halle-Wittenberg, Oral and Maxillofacial Plastic Surgery, Halle, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
03 May 2012 (online)

Abstract

Background Nimodipine is primarily used in subarachnoid hemorrhage (SAH). Clinical trials revealed also a beneficial effect of prophylactic nimodipine treatment on cranial nerve functions following vestibular schwannoma surgery.

Objective The unknown pharmacokinetics of prophylactically administered nimodipine were investigated.

Methods Samples were taken from 27 patients with skull base lesions. Prophylactic intravenous nimodipine infusion was started 5.8–25.8 h (mean 17.9 h) before surgery. Nimodipine concentrations were determined in serum (intra- and postoperatively), cerebrospinal fluid (CSF) (intraoperatively), and tissue samples.

Results Wide interindividual differences were observed. Mean concentrations for nimodipine were 46.9 ng/ml (SD: 6.4; min. 4.1 and max. 92.7 ng/ml) in intraoperative serum, 73.2 ng/ml (SD: 16.7; min. 6.6 and max. 253 ng/ml) in postoperative serum and 8.3 ng/ml (SD: 1.5; min. 1.0 und max. 29.7 ng/ml) in intraoperative CSF. The correlation between intra- and postoperative serum (p=0.004, r=0.560) and between intra­operative serum and CSF concentration (p=0.003, r=0.567) were statistically significant. Furthermore the correlation between intraoperative serum concentration and concentrations collected from vestibular nerves was high (r=0.711), but not statistically significant (p=0.178).

Conclusions Interindividually, continously administered intravenous nimodipine produces considerably variable serum levels. Controls of nimodipine serum concentrations may be useful to optimize nimodipine medication in skull base surgery and in the management of SAH. The serum nimodipine level is a useful marker for CSF and intracranial nerve tissue concentrations of nimodipine.

* This article was originally published online in Central European Neurosurgery on January 12, 2012 (DOI: 10.1055/s-0031-1291207)


 
  • References

  • 1 Tomassoni D, Lanari A, Silvestrelli G , et al. Nimodipine and its use in cerebrovascular disease: evidence from recent preclinical and controlled clinical studies. Clin Exp Hypertens 2008; 30: 744-766
  • 2 Langley MS, Sorkin EM. Nimodipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutical potential in cerebrovascular disease. Drugs 1989; 37: 669-699
  • 3 Allen GS, Ahn HS, Preziose TJ , et al. Cerebral arterial spasm – a controlled trail of nimodipine in patients with subarachnoid haemorrhage. N Engl J Med 1983; 308: 619-624
  • 4 Auer LM. Acute operation and preventive nimodipine improve outcome in patients with ruptured cerebral aneurysms. Neurosurgery 1984; 15: 57-66
  • 5 Ljunggren B, Brandt L, Säveland H , et al. Outcome in 60 consecutive patients treated with early aneurysm operation and intravenous nimodipine. J Neurosurg 1984; 61: 864-873
  • 6 Rinkel GJ, Feigin VL, Algra A , et al. Calcium antagonist for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 2005; CD000277
  • 7 Barker II FG, Ogilvy CS. Efficacy of prophylactic nimodipine for delayed ischemic deficit after subarachnoid haemorrhage: a metaanalysis. J Neurosurg 1996; 84: 405-414
  • 8 Feigin VL, Rinkel GJ, Algra A , et al. Calcium antagonists in patients with aneurysmal subarachnoid haemorrhage: a systematic review. Neurology 1998; 50: 876-883
  • 9 Pickard JD, Murray GD, Illingworth R , et al. Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ 1989; 298: 636-642
  • 10 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 2007; 63: 355-361
  • 11 Angelov DN, Neiss WF, Streppel M , et al. Nimodipine accelerates axonal sprouting after surgical repair of rat facial nerve. J Neurosci 1996; 16: 1041-1048
  • 12 Bischoff B, Romstöck J, Fahlbusch R , et al. Intraoperative brainstem auditory evoked potential pattern and perioperative vasoactive treatment for hearing preservation in vestibular schwannoma surgery. J Neurol Neurosurg Psychiatry 2008; 78: 170-175
  • 13 Guntinas-Lichius O, Martinez-Portillo F, Lebek J , et al. Nimodipine maintains in vivo the increase of GFAP and enhances the astroglial ensheathment of surviving motoneurons in the rat following permanent target deprivation. J Neurocytol 1997; 26: 241-248
  • 14 Mattsson P, Aldskogius H, Svensson M. Nimodipine-induced improved survival rate of facial motor neurons following intracranial transection of the facial nerve in the adult rat. J Neurosurg 1999; 90: 760-765
  • 15 Mattsson P, Janson AM, Aldskogius H , et al. Nimodipine promotes regeneration and functional recovery after intracranial facial nerve crush. J Comp Neurol 2001; 437: 106-117
  • 16 Sekiya T, Yagihashi A, Asano K , et al. Nimodipine ameliorates trauma-induced cochlear neuronal death. Neurol Res 2002; 24: 775-780
  • 17 Scheller C, Strauss C, Fahlbusch R , et al. Delayed facial nerve paresis following acoustic neuroma resection and postoperative vasoactive treatment. Cent Eur Neurosurg 2004; 65: 103-107
  • 18 Scheller C, Richter HP, Engelhardt M , et al. Influence of prophylactic vasoactive treatment on cochlear and facial nerve functions following vestibular schwannoma surgery. A prospective and open-label randomized pilot study. Neurosurgery 2007; 61: 92-98
  • 19 Strauss C, Bischoff B, Neu M , et al. Vasoactive treatment for hearing preservation in acoustic neurinoma surgery. J Neurosurg 2001; 95: 771-777
  • 20 Strauss C, Romstöck J, Fahlbusch R , et al. Preservation of facial nerve function after postoperative vasoactive treatment in vestibular schwannoma surgery. Neurosurgery 2006; 59: 577-584
  • 21 Rämsch KD, Ahr G, Tettenborn D , et al. Overview on pharmacokinetics of nimodipine in healthy volunteers and in patients with subarachnoid haemorrhage. Neurochirurgica 1985; 28 (Suppl. 01) 74-78
  • 22 Vinge E, Andersson KE, Brandt L , et al. Pharmacokinetics of nimodipine in patients with aneurysmal subarachnoid haemorrhage. Eur J Clin Pharmacol 1986; 30: 421-425
  • 23 Bach PR. Determination of nifedipine in serum or plasma by reversed-phase liquid chromatography. Clin Chem 1983; 29: 1344-1348
  • 24 Krol GJ, Noe AJ, Yeh SC , et al. Gas and liquid chromatographic analyses of nimodipine calcium antagonist in blood plasma and cerebrospinal fluid. J Chromatogr 1984; 305: 105-118
  • 25 Nowychy MC, Fox A, Tsien RW. Three types of calcium channel with different calcium agonist sensitivity. Nature 1985; 316: 440-443
  • 26 Kazda S. Pharmacology of nimodipine, a calcium antagonist with preferential cerebrovascular activity. Neurochirurgia 1985; 28: 70-73
  • 27 Towart R, Wehinger E, Meyer H , et al. The effects of nimodipine, its optical isomers and metabolites on isolated vascular smooth muscle. Arzneimittelforschung 1982; 32: 338-346
  • 28 Alborch E, Salom JB, Torregrosa G. Calcium channel in cerebral arteries. Pharmacol Ther 1995; 68: 1-34
  • 29 Horn J, de Haan RJ, Vermeulen M , et al. Nimodipine in animal model experiments of focal cerebral ischemia: a systematic review. Stroke 2001; 32: 2433-2438
  • 30 Suwelack D, Weber H. Assessment of enterohepatic circulation of radioactivity following single dose of C14-nimodipine in the rat. Eur J Drug Metab Pharmacokinet 1985; 10: 231-239
  • 31 Gengo FM, Fagan SC, Krol G , et al. Nimodipine disposition and haemodynamic effects in patients with cirrhosis and age-matched controls. Br J Clin Pharmacol 1987; 23: 47-53
  • 32 Kirch W, Rämsch KD, Dührsen U , et al. Clinical pharmacokinetics of nimodipine in normal and impaired renal function. Int J Clin Pharmacol Res 1984; 4: 381-384
  • 33 Mayberg MR, Batjer HH, Dacey R , et al. Guidelines for the management of aneurysmal subarachnoid haemorrhage. A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 1994; 25: 2315-2328
  • 34 Suarez JI, Tarr RW, Selman WR. Aneurysmal subarachnoid haemorrhage. Current concepts. N Eng J Med 2006; 354: 387-396