Sumatriptan pharmacokinetics

V. F. Cosson, E. Fuseau, C. Efthymiopoulos, and A. Bye, Mixed effect modeling of sumatriptan pharmacokinetics during drug development. I Interspecies allometric sca]ing. J Pharmacokinet Biopharm 25 149-167 (1997). 

E. Ette, P. Williams, J. Lane, Y. K. Kim, and E. V. Capparelli, The determination of population pharmacokinetic model appropriateness. / Clin Pharamcol 43 2-15 (2003). V. F. Cosson, E. Fuseau, C. Efthymiopouios, and A. Bye, Mixed effect modeling of sumatriptan pharmacokinetics during drug development. I. Interspecies allometric scaling. / Pharmacokinet Biopharm 25 149-167 (1997). 

Fox AW. Subcutaneous sumatriptan pharmacokinetics delimiting the monoamine oxidase inhibitor effect. Headache 2010 50 (2) 249-55. 

Other triptans Similar to sumatriptan except for pharmacokinetics (2-6 h duration of action) ... 

Drugs used in the treatment of acute migraine, such as sumatriptan and rizatriptan, are 5-HTiB/iD-receptor agonists and could theoretically interact pharmacodynami-cally with SSRIs to cause serotonin toxicity. Triptans are metabolized mainly by monoamine oxidase, which makes pharmacokinetic interactions with SSRIs unlikely. Although case series have suggested that sumatriptan can be safely combined with SSRIs (SEDA-22, 14), there are occasional reports of toxicity. 

Treatment of 12 healthy volunteers with paroxetine (20 mg/day for 14 days) did not alter the pharmacokinetics or pharmacodynamic effects of an acute dose of rizatriptan (10 mg orally) (29). These data are reassuring, but (as with sumatriptan) it is possible that sporadic cases of 5-HT neurotoxicity could still occur when rizatriptan is combined with an SSRI. 

In an open, randomized, 2-way crossover study in 24 healthy volunteers clarithromycin 500 mg orally every 12 hours for 4 days had no effects on the pharmacokinetics of a single oral dose of sumatriptan 50 mg (29). 

Some of the triptans are metabolized by monoamine oxidase and they should not be used with monoamine oxidase inhibitors. This includes almotriptan (34), rizatriptan (35), sumatriptan (36), and zolmitriptan (28). The effect of moclobemide on the pharmacokinetics of almotriptan was less than with other triptans (34). 

Scott AK. Sumatriptan clinical pharmacokinetics. Clin Pharmacokinet 1994 27(5) 337-44. 

Moore KH, Leese PT, McNeal S, Gray P, O Quinn S, Bye C, Sale M. The pharmacokinetics of sumatriptan when administered with clarithromycin in healthy volunteers. Chn Ther 2002 24(4) 583-94. 

Dechant, K.L. etal. (1992) Sumatriptan. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the acute treatment of migraine and cluster headache. Drugs. 43, 776-798. 

Example Sumatriptan (Imitrex) Route PO, SC, Intranasal Pregnancy category C Pharmacokinetic metabolized in liver and excreted in the urine... 

Fuseau E, Petricoul O, Moore KH, Barrow A, Ibbotson T. Clinical pharmacokinetics of intranasal sumatriptan. Clin Pharmacokinet 2002 41(11) 801-811. 

A single 0.8-g/kg dose of alcohol was given to 16 healthy subjects, followed 30 minutes later by 200 mg of sumatriptan. No statistically significant changes were seen in the pharmacokinetics of sumatriptan. There is nothing to suggest that alcohol should be avoided while taking sumatriptan. 

Kempsford RD, Lacey LF, Thomas M, Fowler PA. The effect of alcohol on the pharmacokinetic profile of oral sumatriptan. Ftmdam Clin Pharmacol (1991) 5, 470. 

In a study in 10 healthy subjects, propranolol 80 mg twice daily for 7 days did not alter the pharmacokinetics of a single 300-mg dose of sumatriptan given on day 7. There was no significant effect on pulse rate or blood pressure. ... 

Flunarizine did not alter the pharmacokinetics or pharmacodynamics of sumatriptan in one study. Flunarizine does not appear to interact with eietriptan. 

A double-blind study found that flunarizine 10 mg daily for 8 days had no effect on the pharmacokinetics of a single dose of sumatriptan, and the... 

VanHeckenAM,DepreM,DeSchepperPJ,FowlerPA,LaceyLF, Durham JM. Lack of effect of flunarizine on the pharmacokinetics and pharmacod3mamics of sumatriptan in healthy volunteers. BrJ Clin Pharmacol (1992) 34, 82-4. 

Erythromycin markedly raises the plasma levels of eletriptan. Clarithromycin, josamycin and troleandomycin are predicted to interact similarly. Almotriptan levels may be raised by erythromycin. Clarithromycin does not significantly alter the pharmacokinetics of sumatriptan. 

A study in which 24 healthy subjects were given sumatriptan 50 mg on the morning of the fourth day of a course of clarithromycin 500 mg twice daily, found that clarithromycin did not significantly affect the pharmacokinetics of sumatriptan. ... 

Selegiline on the other hand had no effect on the pharmacokinetics of zolmitriptan or its metabolites, apart from a small (7%) reduction in its renal clearance. This finding was expected, since selegiline is specific for monoamine oxidase B (but note that this specificity is lost at higher doses). No special precautions would therefore seem to be necessary if selegiline is given with sumatriptan. 

Glaxo Pharmaceuticals UK Limited. A study to determine whedier the pharmacokinetics, safety or tolerability of subcutaneously administered sumatriptan (6 mg) are altered by interaction with concurrent oral monoamine oxidase inhibitors. Data on file (Protocol C92-050),... 

Pizotifen 500 micrograms three times daily for 8 days in 14 healthy subjects was found to have no significant effect on the pharmacokinetics of sumatriptan. In addition, there were no significant changes in blood pressure or heart rate. In a clinieal study, the addition of pizotifen prophylaxis did not alter the efficacy of acute sumatriptan for migraine relief. In this study, the eombination was assoeiated with more weight gain than sumatriptan alone, an effeet whieh was attributed solely to the pizotifen. ... 

No pharmacokinetic interactions or change in adverse effeets were found to oeeur between single 1-mg doses of butorphanol tartrate nasal spray and a 6-mg subeutaneous dose of sumatriptan sueeinate in 24 healthy subjects. It was concluded that concurrent use during aeute migraine attacks need not be avoided. ... 

Srinivas NR, Shyu WC, Upmalis D, Lee JS, Barbhaiya RH. Lack of pharmacokinetic interaction between butorphanol tartrate nasal spray and sumatriptan succinate. J Clin Pharmacol (1995)35,432-7. 

Vachharajani NN, Shyu W-C, Nichola PS, Boulton DW. A pharmacokinetic interaction study between butorphanol and sumatriptan nasal sprays in healthy subjects importance of the timing of butorphanol administration. Cephalalgia (2002) 22,282-7. 

A study in 12 healthy subjects found that a single SOO-mg dose of naproxen had no significant effect on the pharmacokinetics of a single 100-mg oral dose of sumatriptan. ... 

Topiramate does not significantly affect the pharmacokinetics of oral or subcutaneous sumatriptan. 

Oral contraceptives appear to modestly raise the levels of frov-atriptan, naratriptan and zolmitriptan, and slightly increase those of sumatriptan. These changes are not considered clinically significant HRT did not appear to affect the pharmacokinetics of naratriptan. 

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