title: Early-phase pharmacokinetics of enteral and parenteral nimodipine in patients with acute subarachnoid haemorrhage - a pilot study.
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 mug min/ml) were lower in the eight SAH patients receiving enteral nimodipine [AUC(0-4) range: 0.13-5.4 (median: 0.32); AUC(24-28) range: 0.16-6.1 (0.71); AUC(72-76) range: 0.47-20.6 (1.9)] than in the nine patients receiving a continuous intravenous infusion of nimodipine [AUC(0-4) range: 2.4-4.9 (3.4), p=0.059; AUC(24-28) range: 4.7-10.3 (7.3), p=0.001; AUC(72-76) 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.
  
  
  CONCLUSIONS
  This pilot study indicates that the rate and extent of nimodipine 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.
authors.affiliation: Department of Neurosurgery, Kuopio University Hospital, P.O. Box 1777, 70211, Kuopio, Finland. ville.soppi@kuh.fi
authors.forename: Ville
authors.initials: V
authors.lastname: Soppi
authors.forename: Hannu
authors.initials: H
authors.lastname: Kokki
authors.forename: Timo
authors.initials: T
authors.lastname: Koivisto
authors.forename: Marko
authors.initials: M
authors.lastname: Lehtonen
authors.forename: Minna
authors.initials: M
authors.lastname: Helin-Tanninen
authors.forename: Sanna
authors.initials: S
authors.lastname: Lehtola
authors.forename: Jaakko
authors.initials: J
authors.lastname: Rinne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007441:Intubation, Gastrointestinal; D008297:Male; D008875:Middle Aged; D009553:Nimodipine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D010865:Pilot Projects; D012720:Severity of Illness Index; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000145:classification / Q000188:drug therapy*
chemical_list: D002121:Calcium Channel Blockers; D009553:Nimodipine