title: Pharmacokinetics of pyridostigmine in a child with postural tachycardia syndrome.
abstract: Pyridostigmine has been proposed for the treatment of postural orthostatic tachycardia syndrome in adults at a dose of 60 mg twice daily, but no dosing recommendation exists for children. With the approval of our local ethics board, we tested the pharmacokinetics of pyridostigmine in 6 children with myasthenia and a pediatric index patient with severe postural orthostatic tachycardia syndrome whose condition failed all conventional therapy and who had developed significant postural hypertension. Pyridostigmine was quantified by using a validated, semiautomated, and specific high-performance liquid chromatography/tandem mass spectrometry assay in combination with online column-switching extraction and turbo electrospray ionization. The patient with postural orthostatic tachycardia syndrome showed a dose-dependent favorable response to oral pyridostigmine. Pharmacokinetic evaluation revealed a short half-life of 2.29 hours, similar to the 2.0 +/- 0.63 hours in the patients with myasthenia. The patient with postural orthostatic tachycardia syndrome has subsequently been treated at a dose of 45 mg in the morning, 30 mg at lunchtime, and 15 mg at bedtime; after 9 months, there has been persistent positive effect and without additional blood pressure medication. No major adverse effects occurred. Pyridostigmine has been a safe and effective treatment modality for this child with postural orthostatic tachycardia syndrome. The short half-life suggests that dosing 3 times per day is preferable.
authors.affiliation: Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada. guido.filler@lhsc.on.ca
authors.forename: Guido
authors.initials: G
authors.lastname: Filler
authors.forename: Robert M
authors.initials: RM
authors.lastname: Gow
authors.forename: Renisha
authors.initials: R
authors.lastname: Nadarajah
authors.forename: Pierre
authors.initials: P
authors.lastname: Jacob
authors.forename: Gillian
authors.initials: G
authors.lastname: Johnson
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Zhang
authors.forename: Uwe
authors.initials: U
authors.lastname: Christians
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D011187:Posture; D011729:Pyridostigmine Bromide / Q000493:pharmacokinetics*; D013577:Syndrome; D013610:Tachycardia / Q000378:metabolism*
chemical_list: D002800:Cholinesterase Inhibitors; D011729:Pyridostigmine Bromide