Headache, menstruation and combined oral contraceptives: a diary study in 184 women with migraine.

Half of female migraineurs in childbearing age use combined oral contraceptives (COCs), but the influence of COCs on perimenstrual migraine is still unclear. We therefore aimed to analyze the risk of occurrence and persistence (i.e. presence for more than 1 day) of headache and migraine before and during menstruation in women with migraine, comparing users of COCs to non-users. We included 184 women with at least 1 day of menstruation recorded in a 90-day diary. We differentiated between (a) the 2 days before menstruation, (b) the first 3 days of menstruation and (c) the remaining days of menstruation and analyzed subgroups of women with (n=82) and without (n=102) COCs. In both groups, risk of any headache as well as that of migraine was highest during the first 3 days of menstruation with a hazard ratio of 1.9 and 2.1 for non-users and 2.1 and 2.2 for users. Although use of COCs showed no statistically significant overall effect, users were at higher risk for any headache premenstrually and non-users at higher risk for migraine on days 4+ of menstruation. In conclusion, use of COCs exerts only subtle differences on the course of perimenstrual migraine in menstruating women with migraine.

Target site concentrations of ciprofloxacin after single intravenous and oral doses.

To characterize the potential of ciprofloxacin penetration into human soft tissues following intravenous (i.v.) and oral (p.o.) administration, we measured the free ciprofloxacin concentrations in interstitial space fluid of skeletal muscle and subcutaneous adipose tissue by microdialysis. In addition, ciprofloxacin concentrations were measured in cantharis-induced skin blisters, saliva, and capillary plasma and were compared to the total concentrations in venous plasma. Furthermore, a pharmacodynamic in vitro model was used to simulate in vivo pharmacokinetics in bacterial culture. Eight healthy volunteers received ciprofloxacin in an open randomized crossover fashion either as a single i.v. infusion of 400 mg over 60 min or as a single p.o. dose of 500 mg. For both tissues the mean areas under the concentration-time curves (AUCs) for interstitial space fluid (AUC(interstitial fluid)s) were significantly lower than the corresponding AUC(plasma)s, with AUC(interstitial fluid)/AUC(plasma) ratios ranging from 0.38 to 0.68. For skeletal muscle, the AUC(interstitial fluid) was significantly higher after administration of 400 mg i.v. than after administration of 500 mg p.o., with a ratio of the AUC after p.o. administration/AUC after i.v. administration of 0.64. The ratio of the concentration in skeletal muscle/concentration in plasma increased over the entire observation period, implying that ciprofloxacin concentrations were not at steady state. The ratio of the concentration in skin blister fluid/concentration in plasma reached values above 4, indicating a preferential penetration of ciprofloxacin into inflamed lesions. The concentrations in saliva and capillary blood were similar to the corresponding total levels in plasma. In vitro both in vivo ciprofloxacin concentration-time profiles were equally effective against select bacterial strains. In conclusion, single-dose administration of two bioequivalent dosage forms of ciprofloxacin might lead to differences in target site pharmacokinetics. These differences, however, are not related to a difference in target site pharmacodynamics.