Published online October 2, 2006
PEDIATRICS Vol. 118 No. 5 November 2006, pp. e1563-e1568 (doi:10.1542/peds.2006-0904)

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EXPERIENCE & REASON

Pharmacokinetics of Pyridostigmine in a Child With Postural Tachycardia Syndrome

Guido Filler, MD, PhD^a, Robert M. Gow, MB, BS^a, Renisha Nadarajah^a, Pierre Jacob, MD^a, Gillian Johnson, MD^b, Yan-Ling Zhang, PhD^b and Uwe Christians, MD, PhD^b

^a Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada
^b Clinical Research and Development, Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, Colorado

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.

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Key Words: tachycardia • acetylcholine • nervous system • autonomic • pharmacokinetics • children

Abbreviations: POTS, postural orthostatic tachycardia syndrome • HPLC, high-performance liquid chromatography • LC/LC-MS/MS, high-performance liquid chromatography/tandem mass spectrometry assay in combination with online column-switching extraction and turbo electrospray ionization • AUC, area under the time-concentration curve • MRT, mean residence time • C_max, maximum concentration • t_max, time to maximum concentration

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Accepted Jun 5, 2006.

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