title: Absorption kinetics of oral sotalol combined with cisapride and sublingual sotalol in healthy subjects.
abstract: OBJECTIVE
  To study the absorption kinetics of sotalol following administration of different formulations. A formulation which results in fast absorption might be useful in the episodic treatment of paroxysmal supraventricular tachycardia (SVT), atrial fibrillation (Afib) or atrial flutter (Afl).
  
  
  METHODS
  In an open randomized crossover study seven healthy male volunteers were given an intravenous infusion of 20 mg sotalol, for assessing the absolute bioavailability, an oral solution containing 80 mg sotalol, an oral solution containing both 80 mg sotalol and 20 mg cisapride and an 80 mg sotalol tablet, which was taken sublingually.
  
  
  RESULTS
  The addition of cisapride decreased the time at which maximum serum concentrations were reached (tmax) from 2.79 (1.85-4.34) h to 1.16 (0.68-2.30) h (P=0.009) [95% CI: -2.59, -0.55] and increased the absorption rate constant (ka) from 0.49 (0.31-0.69) h(-1) to 1.26 (0.52-5.61) h(-1) (P=0.017). The absolute bioavailability of sotalol was reduced by cisapride from 1.00+/-0.15 to 0.70+/-0.26 (P=0.006), while maximum serum concentrations of both oral solutions were not significantly different. Compared with the sublingually administered tablet with a median tmax of 2.12 (0.89-3.28) h, the sotalol/cisapride oral solution gave a smaller tmax (p=0.009) [95% CI: -1.64, -0.36]. The ka of the sotalol/cisapride solution was significantly (P=0.010) larger than the ka of 0.56 (0.33-0.75) h(-1) found after sublingual administration of the tablet.
  
  
  CONCLUSIONS
  The sotalol/cisapride oral solution might be suitable for the episodic treatment of SVT, Afib or Afl.
authors.affiliation: Department of Clinical Pharmacy, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: V H
authors.initials: VH
authors.lastname: Deneer
authors.forename: L
authors.initials: L
authors.lastname: Lie-A-Huen
authors.forename: J H
authors.initials: JH
authors.lastname: Kingma
authors.forename: J H
authors.initials: JH
authors.lastname: Proost
authors.forename: J C
authors.initials: JC
authors.lastname: Kelder
authors.forename: J R
authors.initials: JR
authors.lastname: Brouwers
mesh_terms: D000284:Administration, Oral; D000286:Administration, Sublingual; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D020117:Cisapride; D018592:Cross-Over Studies; D004338:Drug Combinations; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D013015:Sotalol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013566:Sympathomimetics / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D004338:Drug Combinations; D010880:Piperidines; D013566:Sympathomimetics; D013015:Sotalol; D020117:Cisapride