Introduction
Because of the interindividual variability of kinetic parameters
Triptan | Cmax (ng/ml) | AUC (ng h/ml) | Tmax (h) |
---|---|---|---|
49.5a (13.5) | 266.1a (39.1) | 2.5a (0.7) | |
Eletriptan 20 mg [57] | 61.5b (32.5–116.5) | 317.3b (152.9–658.1) | 1.0c (0.5–1.5) |
Frovatriptan 2.5 mg [58] | 4.2b M (3.19–5.61) | 42.9b M (36.3–50.7) | 2.3c M (2.0–2.5) |
7.0b F (6.02–8.14) | 65.8b F (65.8–134.3) | 3.0c F (2.0–4.0) | |
10.8d M (7.1–14.2) | 108.2d M (76.6–168.1) | 3.0c M (2.0–6.0) | |
16.6d F (9.8–37.3) | 163.6d F (89.9–256.5) | 3.0c F (1.0–6.0) | |
28.6a M (13.5) | 72a (22) | 1.0a (0.5) (range: 0.6–2.4) | |
32.1a F (11.9) | 97a (28) | 1.2a (1.0) (range: 0.4–2.0) | |
Sumatriptan 50 mg [31] | 30.1a (12.5) | 103a (49) | 0.83e (0.33–3.00) |
Sumatriptan 100 mg [33] | 53.2a (29) | 199a (105) | 1.0e (0.5–4.00) |
Zolmitriptan 2.5 mg [18] | 3.0a (1.7) | 17a (8.1) | 2.0c (0.5–6.0) |
3.3e M | 17.7e M | ||
3.8e F | 21.3e F |
Triptan | Male/female ratio of pharmacokinetic parameters | ||||||
---|---|---|---|---|---|---|---|
Bioavailability % | Cmax (ng/ml) | AUC0–∞ (ng h/ml) | Tmax (h) | Vd (L) | t½ (h) | CLp (ml/min) | |
Almotriptan 12.5 mg [22] | NS | NS | NS | NS | – | NS | NS |
Frovatriptan 2.5 mg [21] | 0.88 | 0.60 | 0.46a | 0.66–0.77 | 1.66 | 1.07 | 1.64 |
0.85 | 0.79 | 0.66 | – | – | – | 1.25 | |
– | 0.96 | 0.78 | 0.77 | 1.31 | 0.92 | 1.27 | |
– | 0.89 | 0.74 | 1.00 | 1.38 | 0.92 | 1.22 | |
Zolmitriptan 2.5 mg [18] | 1.00b | 0.87c | 0.83d | 1.54 | 1.04 | 0.90 | 1.13 |
Zolmitriptan 5 mg [18] | 0.78 | 0.62 | 0.56 | – | – | 0.92 | – |
Because the dose-concentration–response relationship is not definite for oral triptans
Because few pharmacokinetic parameters can be used to compare triptans
Because of the variability of oral absorption
Triptan | During/outside migraine attacks ratio of pharmacokinetic parameters | ||
---|---|---|---|
Cmax (ng/ml) | AUC0–∞ (ng h/ml) | Tmax (h) | |
0.93 | 1.00 | 1.23 | |
0.69c | 0.71d | 2.15e | |
Frovatriptan 2.5 mg [58] | 0.93 M | 0.53 | 0.66 |
0.91 F | |||
ND | ND | 1.75–2.33 | |
0.80f | – | – | |
0.75 | 0.56 | 1.6 |
Differences in plasma half-life and recurrence
Differences in bioavailability and consistency of response
Conclusions
Factors | Description |
---|---|
Dynamic variability | Dynamic variability can be studied in isolated tissues. In this case, a considerable variability in the response to triptans is also observed. For example, EC50 varies 51 times for the vasoconstrictive effect of sumatriptan on human cerebral arteries, 21 times for the effect of rizatriptan, and 69 times for the effect of eletriptan [67] |
Variability of the mechanisms implicated in the migraine attack | During the migraine attack various mechanisms are activated. For example, only attacks associated with elevated salivary CGRP levels respond to rizatriptan. This could explain why some patients or attacks are non-triptan responders [68] |
Genetic variability-polymorphisms | STin2 VNTR polymorphism of serotonin transporter gene could be an important genetic factor to confer a higher risk of inconsistent response to triptans in migraine patients [69] |
Mechanisms of receptor adaptation | When an excess of mediator is present in the biophase, a process of desensitisation is activated, which makes receptors refractory. This phenomenon can explain why a second tablet of sumatriptan at 2 h does not increase initial efficacy and does not prevent or delay headache recurrence [70] |
Selection of the patient | The patient must be capable to respond to the drug if we want a response. If the patient takes the triptan for a tension-type headache, the response is improbable, since triptans are not effective in episodic tension-type headache [71] |
Placebo effect | In clinical practice, a patient’s response to an active drug makes us wonder if this patient responds well because of the medication (and its kinetic properties) or because of the placebo effect (caused, for example, by the patient’s positive expectations and by the physician who has prescribed the drug) [72] |
Fluctuation of migraine | The course of migraine can vary in years: changes in this disorder are likely to influence the response to triptans [73] |
Prophylactic treatments | |
Previous therapies | In individuals with migraine, recent prior opioid use reduces triptan response [74] |
Time of medication administration and severity of the migraine attack | The response to triptans is higher and more complete if they are taken early, and when the pain is of mild intensity [26] |