A Pharmacokinetic Interaction Study Between Butorphanol and Sumatriptan Nasal Sprays in Healthy Subjects: Importance of the Timing of Butorphanol Administration

Sumatriptan and butorphanol nasal sprays are commonly used agents for the management of migraine headaches. Under certain circumstances, these two agents may be administered closely in time. However, the possibility of a pharmacokinetic interaction and the safety of this regime have not been examined. In this crossover design study, 24 healthy subjects received the following four treatments, each separated by at least 7 days: 1 mg butorphanol (Stadol NS7®); 20 mg sumatriptan (Imitrex® Nasal Spray); or both formulations together with butorphanol administered either 1 or 30 min after sumatriptan. Serial plasma samples were collected for 24 h post-dose and analysed for butorphanol and/or sumatriptan by HPLC-MS/MS. Butorphanol plasma concentrations were reduced when it was administered 1 min (mean 28.6% decrease in AUC0-∞) , but not 30 min, after sumatriptan. The pharmacokinetics of sumatriptan were not substantially altered by butorphanol. The combination of nasally administered sumatriptan and butorphanol appeared safe. However, if butorphanol nasal spray is administered < 30 min after sumatriptan nasal spray, the analgesic effect of butorphanol may be diminished due to reduced nasal absorption resulting from probable transient vasoconstriction of nasal blood vessels by sumatriptan.

Rhinitis during pregnancy and rhinitis medicamentosa

Vasomotor rhinitis is a nonspecific disorder that is caused neither by infection nor allergy but rather by an imbalance of the autonomic nervous system with a preponderant action of parasympathetic fibers on nasal blood vessels. Rhinitis during pregnancy appears to result from the increased production of estrogen; increased estrogen levels caused by treatment, puberty, or liver disease may also cause rhinitis. Nasal saline mist, antihistamines, and topical corticosteroids are recommended; intranasal corticosteroid injections are also useful but must be administered under expert care. Rhinitis medicamentosa results from overuse of topical vasoconstrictors, which produce a rebound phenomenon. Rebound can also result from numerous medications, including antihypertensive preparations that reduce catecholamine levels, antidepressants, antipsychotics, and tranquilizers. Management of rhinitis medicamentosa consists in limiting the use of vasoconstrictors to no more than 3 days and giving the patient saline nasal sprays, daytime oral vasoconstrictors, and nocturnal antihistamines. Corticosteroids, preferably topical nasal steroids rather than even a short-term course of systemic administration, should also be used.

Vascular Effects of Neuropeptides on Nasal Mucosa

We used dog nasal blood vessels and an in vitro muscle tension-detecting technique to examine the vascular effects of several neuropeptides: Vasoactive intestinal polypeptide, substance P, neurotensin, somatostatin, and neuropeptide Y (NPY). Electrically induced vasoconstriction was inhibited by every peptide except neurotensin, which enhanced this response. Every preparation treated with somatostatin, and one tissue treated with NPY, showed an enhanced noradrenaline-induced contraction. Only NPY caused a tissue contraction. Preparations precontracted by methoxamine were relaxed by every peptide. These results indicate that all peptides examined have marked but varied vasoactivities.