ABSTRACT
Sumatriptan was introduced in 1983, as the first of the triptans, selective 5-hydroxytryptamine (5-HT1B/1D ) receptor agonists, to treat moderate to severe migraine. Migraine predominates in females. Although there have been reports of sex differences in migraine-associated features and pharmacokinetics (PKs) of some triptans, sex differences in the PKs of oral sumatriptan have never been evaluated in Korean. We conducted this study of oral sumatriptan to assess the sex differences in Korean population. Thirty-eight healthy Korean subjects who participated in two separate clinical studies receiving a single oral dose of 50 mg sumatriptan with the same protocols were included in this analysis. A total of 532 sumatriptan concentration observations were used for a population PK modeling. Validation of final population PK model of sumatriptan was performed using bootstrap and visual predictive check. The PK profile of oral sumatriptan was adequately described by a one-compartmental model with combined transit compartment model and a first-order absorption. The covariate analysis showed that the clearance of oral sumatriptan was significantly higher in males than in females (male: 444 L/h, female: 281 L/h). Our results showed that there were sex differences in the clearance of oral sumatriptan. These results encourage further studies to establish the sumatriptan pharmacokinetic-pharmacodynamic model considering sex-related PK differences, which may help to determine optimal dosing regimens for effective treatment of migraine in males and females. Clinical trial registration: CRIS Registration No. KCT0001784.
Subject(s)
Migraine Disorders , Sumatriptan , Female , Humans , Male , Migraine Disorders/drug therapy , Republic of Korea , Serotonin Receptor Agonists , Sex CharacteristicsABSTRACT
BACKGROUND: In acute infarction involving the anterior circulation, the ipsilateral posterior cerebral artery (PCA) often appears to be longer than the contralateral PCA on magnetic resonance angiography. We described this finding as dominant ipsilateral PCA (DIPCA). We sought to find the frequency of DIPCA and its predictors. METHODS: We recruited 164 consecutive individuals with acute infarct involving the anterior circulation, and analyzed their radiological and clinical features. RESULTS: DIPCA was noted in 27 patients (16.5%). It was more frequent in patients with than in patients without steno-occlusive disease of the ipsilateral anterior circulation (30.5 vs. 2.4%, p < 0.001). Multivariate analysis revealed a significant relationship between the severity of arterial lesions in the ipsilateral anterior circulation and DIPCA (p = 0.039). CONCLUSIONS: DIPCA may reflect increased leptomeningeal collateral flow via the ipsilateral PCA, and its development may be dependent on the stenotic anterior circulation.
