title: Prophylactic intravenous nimodipine treatment in skull base surgery: pharmacokinetic aspects.
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 intra-operative 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.
authors.affiliation: University of Halle-Wittenberg, Department of Neurosurgery, Halle (Saale), Germany. christian.scheller@uk-halle.de
authors.forename: C
authors.initials: C
authors.lastname: Scheller
authors.forename: A-S
authors.initials: AS
authors.lastname: Vogel
authors.forename: S
authors.initials: S
authors.lastname: Simmermacher
authors.forename: J C
authors.initials: JC
authors.lastname: Rachinger
authors.forename: J
authors.initials: J
authors.lastname: Prell
authors.forename: C
authors.initials: C
authors.lastname: Strauss
authors.forename: M
authors.initials: M
authors.lastname: Reinsch
authors.forename: U
authors.initials: U
authors.lastname: Kunter
authors.forename: A
authors.initials: A
authors.lastname: Wienke
authors.forename: J
authors.initials: J
authors.lastname: Neumann
authors.forename: K
authors.initials: K
authors.lastname: Scheller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000768:Anesthesia, General; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D004428:Ear Neoplasms / Q000601:surgery; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008579:Meningioma / Q000601:surgery; D008875:Middle Aged; D009464:Neuroma, Acoustic / Q000601:surgery; D009553:Nimodipine / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D019291:Skull Base / Q000601:surgery*; D021241:Spectrometry, Mass, Electrospray Ionization; D014725:Vestibular Nerve / Q000378:metabolism; D055815:Young Adult
chemical_list: D002121:Calcium Channel Blockers; D009553:Nimodipine