title: Increased bioavailability of phenylephrine by co-administration of acetaminophen: results of four open-label, crossover pharmacokinetic trials in healthy volunteers.
abstract: OBJECTIVE
  Over-the-counter combinations containing acetaminophen and phenylephrine for treatment of the common cold and influenza are widespread, but there are few data about pharmacokinetics of these two drugs used in combination. We aimed to investigate pharmacokinetic interactions between acetaminophen and phenylephrine.
  
  
  METHODS
  A series of four randomised, open-label, crossover studies investigating phenylephrine and acetaminophen combination pharmacokinetics were undertaken (n = 28, 30, 6 and 26) using standard non-compartmental analyses. Time-concentration observations from these four studies were pooled to examine the interaction between these two compounds. Data were analysed using non-linear mixed effects models.
  
  
  RESULTS
  Non-compartmental analyses showed an approximate doubling of phenylephrine plasma concentration when the standard 10-mg dose was administered in combination with acetaminophen. Population analysis was based on data from 90 subjects with 2050 observations. The relative bioavailability of phenylephrine 10 mg was doubled (Fbio 2.11, 95%CI 1.89, 2.31) when combined with acetaminophen 1000 mg, while the absorption half-time was reduced by 50 %. When combined with 500 mg of acetaminophen, bioavailability increased by 64 % (Fbio 1.64). Phenylephrine 5 mg in combination with acetaminophen 1000 mg produced a phenylephrine plasma time-concentration profile similar to that seen with phenylephrine 10 mg administered alone.
  
  
  CONCLUSIONS
  The relative bioavailability of phenylephrine was increased when co-administered with acetaminophen.
authors.affiliation: AFT Pharmaceuticals Ltd, P O Box 33-203, Takapuna, Auckland, 0740, New Zealand.
authors.forename: Hartley C
authors.initials: HC
authors.lastname: Atkinson
authors.forename: Ioana
authors.initials: I
authors.lastname: Stanescu
authors.forename: Isam I
authors.initials: II
authors.lastname: Salem
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Potts
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Anderson
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000328:Adult; D000483:Alleles; D015239:Arylsulfotransferase / Q000235:genetics; D001682:Biological Availability; D018592:Cross-Over Studies; D004338:Drug Combinations; D004347:Drug Interactions; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage; D008297:Male; D008954:Models, Biological; D010656:Phenylephrine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D010656:Phenylephrine; D000082:Acetaminophen; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; D007052:Ibuprofen