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Pharmacokinetic Variability of Drugs Used for Prophylactic Treatment of Migraine

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Abstract

In this review, we evaluate the variability in the pharmacokinetics of 11 drugs with established prophylactic effects in migraine to facilitate ‘personalized medicine’ with these drugs. PubMed was searched for ‘single-dose’ and ‘steady-state’ pharmacokinetic studies of these 11 drugs. The maximum plasma concentration was reported in 248 single-dose and 115 steady-state pharmacokinetic studies, and the area under the plasma concentration-time curve was reported in 299 single-dose studies and 112 steady-state pharmacokinetic studies. For each study, the coefficient of variation was calculated for maximum plasma concentration and area under the plasma concentration-time curve, and we divided the drug variability into two categories; high variability, coefficient of variation >40%, or low or moderate variability, coefficient of variation <40%. Based on the area under the plasma concentration-time curve in steady-state studies, the following drugs have high pharmacokinetic variability: propranolol in 92% (33/36), metoprolol in 85% (33/39), and amitriptyline in 60% (3/5) of studies. The following drugs have low or moderate variability: atenolol in 100% (2/2), valproate in 100% (15/15), topiramate in 88% (7/8), and naproxen and candesartan in 100% (2/2) of studies. For drugs with low or moderate pharmacokinetic variability, treatment can start without initial titration of doses, whereas titration is used to possibly enhance tolerability of topiramate and amitriptyline. The very high pharmacokinetic variability of metoprolol and propranolol can result in very high plasma concentrations in a small minority of patients, and those drugs should therefore be titrated up from a low initial dose, depending mainly on the occurrence of adverse events.

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Fig. 1

Reproduced from Tfelt-Hansen and Edvinsson [55], with permission

Fig. 2

Reproduced from Tfelt-Hansen and Edvinsson [55], with permission

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Authors and Affiliations

  1. Danish Headache Center, Department of Neurology, Rigshospitalet-Glostrup Hospital, University of Copenhagen, Glostrup, Denmark

    Peer Tfelt-Hansen & Agniezka Pavbro

  2. Department of Cardiology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark

    Frederik Nybye Ågesen & Jacob Tfelt-Hansen

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  1. Peer Tfelt-Hansen
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Correspondence to Frederik Nybye Ågesen.

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This study was funded by the Novo Nordisk Foundation.

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Peer Tfelt-Hansen, Frederik Nybye Ågesen, Agniezka Pavbro, and Jacob Tfelt-Hansen have no conflicts of interest directly relevant to the content of this article.

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Tfelt-Hansen, P., Ågesen, F.N., Pavbro, A. et al. Pharmacokinetic Variability of Drugs Used for Prophylactic Treatment of Migraine. CNS Drugs 31, 389–403 (2017). https://doi.org/10.1007/s40263-017-0430-3

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