JP2006522790A - Pharmaceutical combination comprising eletriptan and sodium bicarbonate - Google Patents

Abstract

The present invention provides a combination comprising (a) eletriptan or a pharmaceutically acceptable salt thereof, and (b) sodium bicarbonate. The combination provides rapid absorption of eletriptan when taken orally. Said combination is useful for the treatment or prevention of diseases with indications of 5-HT ₁ agonists, in particular for the treatment of migraine or the prevention of migraine recurrence.

Description

The invention relates to a combination comprising eletriptan or a pharmaceutically acceptable salt thereof and sodium bicarbonate, the use of such a combination for the treatment or prevention of a disease for which a 5-HT ₁ agonist is indicated, and It relates to a formulation or product comprising such a combination.

  Eletriptan, 3-{[1-methylpyrrolidin-2 (R) -yl] methyl} -5- (2-phenylsulfonylethyl) -1H-indole and a process for its preparation are disclosed in US Pat. No. 5,607,951. The

Eletriptan is a potent 5-HT ₁ agonist, and high blood pressure, depression, anxiety, eating disorders, vomiting, drug abuse, cluster headaches, migraines (including menstrual and recurrent migraines), Used to treat pain, chronic paroxysmal migraine, or headache related to vascular disorders (see US-B-5,607,95, WO-A-96 / 06842, and WO-A-00 / 32589) ).

Eletriptan is a treatment for headaches in children, treatment for mild migraines, treatment for menstrual and early migrains, and post-traumatic head and neck damage, mixed headache and tension Useful in the treatment of headaches.
As disclosed in WO-A-00 / 06161, eletriptan is also useful for preventing recurrent migraine.

  Pharmaceutical compositions suitable for oral administration of eletriptan, or pharmaceutically acceptable salts thereof, such as tablets or capsules, are pharmaceutically acceptable, such as adhesives, bulking agents, lubricants, disintegrants, or humidifiers. It is known to be prepared by traditional means using excipients.

Such a composition dissolves in the gastrointestinal tract and the released drug is absorbed into the bloodstream after a certain time lag. For example, when eletriptan is administered in the form of the α-polymorphic hydrobromide disclosed in WO-A-96 / 06842, standard tablets and the maximum of the drug in the bloodstream (T _max ) It is observed that plasma concentrations range from about 1 hour in fasted patients to about 4 hours in patients who eat.

The problem is that by causing gastric fluid flow arrest, seizures of migraine can further increase T _max , which delays drug absorption. For example, in a study with or without migraine when 30 mg of eletriptan was administered to 34 fasting subjects, compared to patients without migraine (T _max 1.3 ± 1.3 h), T _max was Significantly slower in patients with headache (T _max 2.8 ± 2.1 h).

  Clearly, there is a need to minimize the time lag between oral administration of eletriptan or its pharmaceutically acceptable salts and relief of symptoms caused by delivery of the drug to the tissue of interest by the bloodstream To do.

When eletriptan or a pharmaceutically acceptable salt thereof is administered as a combination with sodium bicarbonate via the oral route, the time lag between oral administration and the maximum plasma level of the drug is dramatically reduced, It was surprisingly found that the case was shortened to about 30 minutes. The patient's benefit resulting from a reasonably fast improvement in symptoms is self-evident.
Accordingly, the present invention provides a combination of eletriptan or a pharmaceutically acceptable salt thereof and sodium bicarbonate.

The present invention further provides a combination of eletriptan or a pharmaceutically acceptable salt thereof and sodium bicarbonate for pharmaceutical use.
The present invention relates to eletriptan or a pharmaceutically acceptable salt thereof for use in the treatment or prevention of a disease for which a 5-HT ₁ agonist is indicated, in particular for the treatment of migraine or for the prevention of migraine recurrence. Further provided is a combination of sodium bicarbonate.

The present invention relates to (a) eletriptan or a medicament for the manufacture of a medicament for the treatment or prevention of a disease for which a 5-HT ₁ agonist is indicated, in particular for the treatment of migraine or the prevention of migraine recurrence. Further provided is the use of a salt thereof, or (b) sodium bicarbonate, wherein (a) and (b) are taken separately, sequentially or simultaneously by the oral route.

The invention relates to a method of treating or preventing a disease in which a 5-HT ₁ agonist is indicated in mammals, including humans, in particular a method of treating migraine or preventing recurrence of migraine, Further provided is the above method comprising the simultaneous, separate or sequential administration of an effective amount of eletriptan or a pharmaceutically acceptable salt thereof and (b) an effective amount of sodium bicarbonate by oral route. To do.

The present invention further provides a pharmaceutical composition suitable for oral administration comprising eletriptan, or a pharmaceutically acceptable salt thereof, sodium bicarbonate, and a pharmaceutically acceptable excipient, diluent, or carrier. .
The present invention provides a combined formulation for simultaneous, separate or sequential use by oral administration in the treatment or prevention of diseases with indications of 5-HT ₁ agonists, in particular the treatment of migraine or the prevention of migraine recurrence And (a) eletriptan or a pharmaceutically acceptable salt thereof and (b) sodium bicarbonate.
The pharmaceutically acceptable salts of eletriptan include its acid addition salts and its basic salts.

  Suitable acid addition salts are formed from acids that form non-toxic salts. Examples are acetic acid, aspartate, benzoate, besylate, bicarbonate / carbonate, bisulfate / sulfate, borate, cansylate, citrate, edisylate, methylate, formate Salt, fumarate, glucoceptate, gluconate, glucuronate, hexafluorophosphate, hibenzate, hydrochloride / chloride, hydrobromide / bromide, hydroiodide / iodide, Isethionate, lactate, malate, maleate, malonate, methylate, methylsulfate, naphthylate, 2-naphthylate, nicotinate, nitrate, orotate, oxalate , Palmitate, pamoate, phosphate / hydrogen phosphate / dihydrogen phosphate, saccharate, stearate, succinate, tartrate, tosylate, and trifluoroacetate.

  Suitable basic salts are formed from bases that form non-toxic salts. Examples include the salts of aluminum, arginine, benzathine, calcium, choline, diethylamine, diolamine, glycine, lysine, magnesium, meglumine, olamine, potassium, sodium, tromethamine, and zinc.

For a review of suitable salts, see “Handbook of Pharmaceutical Salts: Properties, Selection, and Use” by Stahl and Wermuth (Wiley-VCH, Weinheim, Germany, 2002).
Preferred salts of eletriptan in the context of the present invention are hydrobromides and hemisulfates (see WO-A-96 / 06842 and WO-A-01 / 23377), in particular hydrobromides. is there.

The pharmaceutically acceptable salt of eletriptan can be readily prepared by mixing together eletriptan and the desired acid or base, if desired. The salt precipitates out of solution and is recovered by filtration or is recovered by evaporation of the solvent.
Similarly, hydrates, and crystallization solvent isotopically substituted may solvates (e.g., D ₂ O, d ₆ - acetone, d _6-DMSO) solvent pharmaceutically acceptable eletriptan including Japanese compounds are within the scope of the present invention.

  Similarly, an inclusion complex, a drug-host inclusion complex in which the drug and host are present in stoichiometric or non-stoichiometric amounts, as opposed to the solvates described above. complexes) are within the scope of the present invention. For a review of such complexes, see J. Pharm. Sci. 64 (8), 1269-1288 (August 1975) by Haleblian.

  Any polymorph of eletriptan, or a pharmaceutically acceptable salt thereof, can be used in the present invention. Particularly preferred are α-polymorphs of eletriptan hydrobromide as described in WO-A-96 / 06842 and eletriptan hemisulphate as defined by the claims of WO-A-01 / 23377 It is a polymorphism of, especially the former.

  Similarly, so-called “prodrugs” of eletriptan and pharmaceutically acceptable salts thereof are within the scope of the invention. Thus, certain derivatives of eletriptan and its salts, which themselves have little or no pharmacological activity, can be obtained by administration into or on the body, for example by metabolism or hydrolytic cleavage. Can be converted to itself. Such derivatives are called “prodrugs”. Details on the use of prodrugs can be found in 'Pro-drugs as Novel Delivery Systems', Vol. 14, ACS Symposium Series (T Higuchi and W Stella) and 'Bioreversible Carriers in Drug Design', Pergamon Press, 1987 (ed. EB Roche, American Pharmaceutical Association).

  Prodrugs according to the present invention are suitable for those skilled in the art described for example in the appropriate functionality present in eletriptan as “pro-moieties” in “Design of Prodrugs” (Elsevier, 1985) by H Bundgaard, for example. It can be manufactured by replacing certain known parts.

In the case of eletriptan, a particularly important prodrug is a derivative of the indole NH group, for example by substitution of a hydrogen atom with a (C ₁ -C ₁₀ ) alkanoyl.

Similarly, the present invention includes all pharmaceutically acceptable isotopic variants of eletriptan and pharmaceutically acceptable salts thereof. Isotopic variants are defined as having at least one atom replaced with an atom having the same atomic number but a different atomic mass than is normally found in nature. Examples of possible isotopes are hydrogen isotopes such as ² H and ³ H, carbon isotopes such as ¹³ C and ¹⁴ C, nitrogen isotopes such as ¹⁵ N, oxygen isotopes such as ¹⁷ O and the like. ¹⁸ O, phosphorus isotopes such as ³² P, sulfur isotopes such as ³⁵ S, fluorine isotopes such as ¹⁸ F, and chlorine isotopes such as ³⁶ CI.

Substitution with isotopes such as deuterium, i.e. ² H, provides advantages for certain therapies obtained from greater metabolic stability, e.g. long in vivo half-life or low dose requirements, It may therefore be preferable in some circumstances.
For example, certain isotopic variants, such as those incorporating radioactive isotopes, are useful for drug and / or substrate tissue distribution studies. The radioactive isotopes tritium, ie ³ H, and carbon-14, ie ¹⁴ C, are particularly useful for this purpose in terms of easy detection and ready detection means.

Isotopic variants of eletriptan and its salts are described in the art for the preparation of eletriptan using traditional techniques known to those skilled in the art, or appropriate isotope variants of suitable reagents. Can generally be made by methods similar to those described.
Eletriptan or a pharmaceutically acceptable salt thereof and sodium bicarbonate (hereinafter “compounds of the invention”) are lyophilized, spray dried or dried by evaporation to a crystalline Alternatively, a solid plug, powder, or film of an amorphous material is provided. Microwave or radio frequency drying can be used for this purpose.

While the compounds of the invention can be administered alone, they are generally administered as a formulation with one or more pharmaceutically acceptable excipients. The term “excipient” is used herein to describe all ingredients other than the compounds of the invention.
The compounds of the present invention are administered orally. Formulations suitable for oral administration include, for example, solid formulations such as tablets, capsules (including microparticles, liquids or powders), lozenges (including liquids), chews, multi- and nano-microparticles, gels (mucoadhesion) Including film), ovules, sprays, and solutions.

Solutions include suspensions, solutions, syrups, and elixirs. Such formulations are utilized as fillers in soft or hard capsules and contain a carrier such as water, ethanol, propylene glycol, methylcellulose, or a suitable oil, and one or more emulsifiers and / or suspending agents. May include in general. Similarly, the solution can be prepared by returning from a solid, for example a sachet.
Similarly, compounds of the present invention may be used in readily dissolvable, rapidly disintegrating dosage forms, such as those described in Expert Opinion in Therapeutic Patents, 11 (6), 981-986 (2001) by Liang and Chen. It may be.

  Tablets generally contain a disintegrant. Examples of disintegrants include glycerin / starch / sodium, carboxymethylcellulose / sodium, carboxymethylcellulose / calcium, croscarmellose / sodium, crospovidone, polyvinylpyrrolidone, methylcellulose, microcrystalline cellulose, hydroxypropyl substituted by lower alkyl Contains cellulose, starch, pregelatinized starch, and sodium alginate. Generally, the disintegrant comprises 1 wt% to 25 wt% of the dosage form, preferably 5 wt% to 20 wt%. It is preferred that tablets made in accordance with the present invention should contain microcrystalline cellulose as a disintegrant.

  Binders are commonly used to add cohesive properties to tablet formulations. Suitable binders include microcrystalline cellulose, gelatin, sugar, polyethylene glycol, natural and synthetic gums, polyvinyl pyrrolidone, pregelatinized starch, hydroxypropyl cellulose, and hydroxypropyl methylcellulose. Similarly, tablets can be produced from, for example, lactose (such as monohydrate, spray-dried monohydrate, anhydrous), mannitol, xylitol, dextrose, sucrose, sorbitol, microcrystalline cellulose, starch, and hydrogen phosphate May contain diluents such as calcium dihydrate. The tablets made according to the present invention should preferably contain microcrystalline cellulose as a binder.

  Similarly, tablets may optionally include surface active agents such as sodium lauryl sulfate and polysorbate 80, and glidants such as silicon dioxide and talc. When provided, the surfactant may comprise 0.2 wt% to 5 wt% of the tablet, and the glidant may comprise 0.2 wt% to 1 wt% of the tablet.

Similarly, tablets typically contain a lubricant, such as magnesium stearate, calcium stearate, zinc stearate, sodium stearyl fumarate, and a mixture of magnesium stearate and sodium lauryl sulfate. Lubricants are generally included from 0.25 wt% to 10 wt%, preferably from 0.5 wt% to 3 wt% of the tablet. It is preferred that tablets made according to the present invention should contain magnesium stearate as a lubricant.
Other possible ingredients include antioxidants, colorants, flavoring agents, preservatives, and taste-making agents.

A typical tablet has a maximum of about 80% drug, about 10 wt% to about 90 wt% binder, about 0 wt% to about 85 wt% diluent, about 2 wt% to about 10 wt% disintegrant, and about 0.25. Contains wt% to about 10wt% lubricant.
Tablet blends are compressed directly or by roller to form tablets. Alternatively, the tablet mixture or part of the mixture may be wet-, dry-, or melt-granulated, melt-solidified, or extruded prior to tableting. The final dosage form may contain one or more layers, or may or may not be coated; it can even be encapsulated.
Tablet dosage forms are described in "Pharmaceutical Dosage Forms: Tablets, Vol. 1", by H. Lieberman and L. Lachman, Marcel Dekker, NY, NY, 1980 (ISBN 0-8247-6918-X). .

  The compounds of the present invention are combined with soluble polymers such as, for example, cyclodextrins or polyethylene glycol-containing polymers to improve their solubility, disintegration rate, flavor, bioavailability, and / or stability. sell. Both inclusion and non-inclusion complexes can be used. As an alternative to direct complexation with the drug, cyclodextrin can be used as an auxiliary additive, ie as a carrier, diluent or solubilizer. Alpha-, beta-, and gamma-cyclodextrins are used for these purposes, as examples are found in international patent applications WO-A-91 / 11172, WO-A-94 / 02518, and WO-A-98 / 55148. Most commonly used for.

  For administration to human patients, the total daily dose of eletriptan is generally in the range of 0.1 mg to 4 mg / kg in single or divided doses. A 40mg single dose is currently recommended. Regardless, the physician will determine the actual dosage that will be most suitable for any individual patient and will vary with the age, weight and response of the particular patient. There may, of course, be individual instances where the above dosages are exemplary of the average case, and high or low dosage ranges may be appropriate, and such are within the scope of this invention.

  Thus, the tablets or capsules according to the invention generally contain 5 to 240 mg, preferably 5 to 100 mg of eletriptan for single or more administrations as required. In a particularly preferred embodiment of the invention, (a) 40 mg eletriptan in its hydrobromide form for administration alone, or (b) its hydrobromide salt for two administrations at a time A tablet containing 20 mg of eletriptan in the form of is provided.

  To obtain serum (150 mM) and nearly isotonic duodenal concentrations, preferably enough sodium bicarbonate should be administered. So, for example, 1260 mg of sodium bicarbonate is needed to provide such an isotonic solution when a fasting volunteer is to be ingested with half a tumbler of water (100 ml). Is done. Such an amount of sodium bicarbonate is too much to be conveniently incorporated into one tablet. Thus, if the combination is to be administered in the form of a tablet at the same time, it is preferred to provide a tablet comprising about 630 mg sodium bicarbonate for administration two at a time. Alternatively, if the combination of the present invention is to be taken with 50 ml of water, one tablet containing about 630 mg of sodium bicarbonate is preferred.

In one embodiment, a combination or formulation (especially a tablet) according to the invention comprises more than 50% (more preferably more than 55%) sodium bicarbonate.
Preferably, eletriptan or a salt thereof and bicarbonate ions are administered simultaneously, preferably in the form of a tablet containing both compounds.
Preferably, such tablets comprise (in the form of its hydrobromide salt 20-40 mg eletriptan) in combination with 300-1300 mg, most preferably about 630 mg sodium bicarbonate.
Preferably, such tablets contain 20-40 mg (in the form of its hydrobromide), most preferably 20 or 40 mg eletriptan in combination with about 630 mg sodium bicarbonate.

Similarly, the combination of eletriptan or a pharmaceutically acceptable salt thereof and sodium bicarbonate can be administered in combination with one or more additional active ingredients. Examples of such further active ingredients include:
(A) Further anti-migraine drugs, in particular further triptans such as sumatriptan, naratriptan, rizatriptan, almotriptan, abitriptan, frovatriptan or zolmitriptan;
(B) Exercise promoters, such as those described in WO-A-02 / 070070, such as metoclopramide;
(C) alkylxanthine compounds such as caffeine, theophylline or theobromine, in particular caffeine; and (d) non-steroidal anti-inflammatory drugs (NSAIDs) such as COX-2 inhibitors such as celecoxib or valdecoxib.

  In a further aspect of the invention, similarly, the combination of eletriptan or a salt thereof and sodium bicarbonate is further pharmaceutically, such that when exposed to an aqueous medium, the combination dissolves in an effervescent manner. May contain acceptable acidic agents. Examples of suitable pharmaceutically acceptable acidic agents include adipic acid, ascorbic acid, citric acid, fumaric acid, glycolic acid, lactic acid, maleic acid, meso oxalic acid, succinic acid, and tartaric acid. Citric acid and adipic acid are preferred.

It should be appreciated that all references herein to treatment include therapy, pain relief, and prophylactic treatment.
The combination of the present invention may conveniently be provided in the form of a tablet with a suitable amount of water that the tablet can be taken together.
Accordingly, the present invention further provides an article comprising (a) eletriptan or a pharmaceutically acceptable salt thereof, (b) sodium bicarbonate, (c) water, and (d) a suitable package.

  Preferably, such is (a) two tablets each containing 20 mg eletriptan (in its hydrobromide form), about 630 mg sodium bicarbonate, and about 100 ml water; Or (b) either one tablet containing 40 mg eletriptan (in its hydrobromide form), about 630 mg sodium bicarbonate, and about 50 ml water.

Although the present invention has been described above solely with respect to eletriptan or a pharmaceutically acceptable salt thereof, in order to obtain an increase in gastrointestinal absorption when any 5-HT ₁ agonist is delivered by the oral route, in principle. As shown, it can be combined with sodium bicarbonate. Such 5-HT ₁ agonists include almotriptan, alnatriptan, abitriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan.
Accordingly, the present invention further provides a non-foamable composition adapted for oral administration and gastrointestinal drug absorption comprising a 5-HT ₁ agonist and sodium bicarbonate.

In this context, non-foaming means that no foaming is observed when the composition is dissolved in pH 7 water.
As noted above, all preferred features associated with the combination of eletriptan and sodium bicarbonate apply equally to non-foaming compositions comprising a 5-HT ₁ agonist and sodium bicarbonate. In particular, in one embodiment, the composition comprises greater than 50% by weight (more preferably greater than 55%) sodium bicarbonate.
The following examples illustrate the invention.

Example 1-4
Tablets containing eletriptan hydrobromide and sodium bicarbonate Eletriptan hydrobromide (24.24 mg, equivalent to 20 mg eletriptan free base), sodium bicarbonate (USP, 630 mg), and microcrystalline cellulose (Avicel PH 102, Ph. Eur., 137.76 mg) were mixed for 10 minutes, passed through a 500 μM sieve and mixed for an additional 10 minutes. Sieve intragranular magnesium stearate (Ph. Eur., 8 mg) was added and the mixture was smoothed for 5 minutes. The resulting mixture was found to have a particle size range of about 200 μm to 1 mm and excellent flow characteristics. The mixture was tableted by the direct tableting method. The tablets so produced had excellent weight uniformity and friability.

  Surprisingly, eletriptan in a 2.5% w / w tablet composition can give the tablet extra strength, evidenced by an increase in tablet hardness of 0.7 kp compared to tablets made from placebo blends. Is done.

  Examples 2-4 in Table 1 illustrate additional tablets made according to the method of Example 1. In the case of Examples 3 and 4, lactose and croscarmellose sodium were added to the initial mixture before combining.

Example 5
Pharmacokinetic Evaluation of Eletriptan Hydrobromide / Sodium Bicarbonate Tablets Compared to Standard Eletriptan Hydrobromide Tablets The purpose of this study was to The eletriptan plasma concentration in 4 beagle dogs after administration of tablets containing triptan is measured, thereby determining sodium bicarbonate judgment on eletriptan absorption and rate of exposure.

The following two formulations were compared:
(A) a commercially available 20 mg tablet containing eletriptan hydrobromide ingested with 50 ml of water; and (b) the tablet of Example 1 ingested with 50 ml of water.

  Four beagles, 2 males and 2 females, were used in the study. Each beagle was given one of the study formulations, and subsequently blood samples were taken for 24 hours (every 5 minutes for the first 45 minutes) to monitor eletriptan plasma levels. The beagle was followed by another dosage form and blood samples were taken in the same manner. There was at least one week between treatments.

The results of the study are listed in Table 2. Mean values of key pharmacokinetic parameters T _max (time to maximum plasma concentration), C _max (maximum plasma concentration), and AUC (total drug exposure minus the area under the curve from 0 to infinity) , Given as the mean value for each dog. In the case of dosage form (b), one dog vomited 15 minutes after treatment, giving anomalous results that were not included in the calculation. Similarly, the standard deviation from the mean value is listed.

The result is 2.8 hours shorter T _max to average the average from 1.2 hours (± 2.2) (± 0.3) , i.e. as indicated by the average shorter, 57% of the T _max, 20 mg with 50ml of water It was shown that administration of a tablet containing eletriptan and 630 mg sodium bicarbonate resulted in a faster absorption of the drug than administration of a commercial 20 mg eletriptan tablet with 50 ml water. The corresponding increase in C _max is from an average of 22.6 ng / ml to an average of 31.8 ng / ml. The overall exposure measured by AUC is similar. Furthermore, inter-animal variability was greatly reduced after administration of the dosage form (b) containing sodium bicarbonate when compared to administration of the standard dosage form (a).

Claims (15)

  A combination comprising (a) eletriptan or a pharmaceutically acceptable salt thereof, and (b) sodium bicarbonate.   The combination according to claim 1, wherein (a) is eletriptan hydrobromide or eletriptan hemisulfate.   3. A combination according to claim 1 or 2 for use as a medicament. 3. A combination according to claim 1 or 2 for use in the treatment or prevention of diseases with indications of 5-HT ₁ agonists, in particular the treatment of migraine or the prevention of migraine recurrence. (A) eletriptan or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment or prevention of diseases with indications of 5-HT ₁ agonists, in particular for the treatment of migraine or prevention of migraine recurrence, or (B) Use of sodium bicarbonate, wherein (a) and (b) above should be taken separately, sequentially or simultaneously by oral route. A method of treating or preventing a disease with an indication of a 5-HT ₁ agonist in a mammal, including a human, particularly a method of treating migraine or preventing migraine recurrence, comprising: (a) an effective amount of Said method comprising administering eletriptan or a pharmaceutically acceptable salt thereof and (b) an effective amount of sodium bicarbonate simultaneously, separately or sequentially by oral route.   7. The use according to claim 5 or the method according to claim 6, wherein (a) is eletriptan hydrobromide or eletriptan hemisulfate.   A pharmaceutical composition adapted for oral administration comprising the combination according to claim 1 or 2 and a pharmaceutically acceptable excipient.   9. A pharmaceutical composition according to claim 8 in the form of a tablet.   10. The pharmaceutical composition of claim 9, comprising eletriptan hydrobromide, sodium bicarbonate, microcrystalline cellulose, and magnesium stearate. (A) as a combined preparation for simultaneous, separate or sequential use by oral administration in the treatment or prevention of diseases with indications of 5-HT ₁ agonists, in particular migraine treatment or prevention of migraine recurrence Eletriptan or a pharmaceutically acceptable salt thereof, and (b) a product comprising sodium bicarbonate.   12. An article according to claim 11, comprising any one of the compositions according to any one of claims 8-10.   13. The article of claim 11 or 12, further comprising an amount of water suitable for facilitating oral administration of the eletriptan or salt thereof and sodium bicarbonate.   (A) 2 tablets each containing 20 mg eletriptan (in its hydrobromide form) and about 630 mg sodium bicarbonate and about 100 ml water, or (b) 40 mg (its bromide) 14. The article of claim 13 comprising any of a tablet comprising eletriptan (in the form of a hydrogenate salt) and about 630 mg sodium bicarbonate and about 50 ml water. A non-foaming composition adapted for oral administration and gastrointestinal drug absorption comprising a 5-HT ₁ agonist and sodium bicarbonate.