AimsThe aims of the study were to: (1) evaluate the gastrointestinal transit, release and absorption of budesonide from tablets with a new multimatrix formulation (M MX®) designed to release the drug throughout the whole colon, and (2) assess the influence of food on budesonide bioavailability. MethodsTwo phase I studies, each comprising 12 healthy males, were performed. Gastrointestinal transit of 153 Sm-labelled tablets containing 9 mg budesonide was evaluated by means of pharmaco-scintigraphy. The effect of food was tested by comparing plasma pharmacokinetics after intake of a high fat and high calorie breakfast with fasting controls. Results153 Sm-labelled tablets reached the ascending colon after a mean ± SD 9.8 ± 6.9 h. Initial tablet disintegration was observed in the ileum in 42% and the ascending and transverse colon in 33% of subjects. Ninety-six per cent of the dose was absorbed into the systemic circulation during passage through the whole colon including the sigmoid. Food significantly decreased C max values from 1429 ± 1014 to 1040 ± 601 pg mL − 1 ( P = 0.028) and AUC values from 14 814 ± 11 254 to 13 486 ± 9369 pg h − 1 mL − 1 ( P = 0.008). Mean residence time and t max increased by 12-29%. There was no drug accumulation after 1 week of once daily oral administration of budesomide. ConclusionsMMX®-budesonide tablets appear suitable for targeted colonic drug delivery. Transit parameters and low systemic bioavailability warrant further studies with the new formulation.

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The two formulations tested were similarly effective in increasing DHA and EPA concentrations in plasma and lysed whole blood, and showed comparable bioavailability for both active components.

The aim of this study was to evaluate the pressor response to oral tyramine during repeated administration of oral safinamide in healthy volunteers. Twelve females and eight males aged 52.7 ± 4.9 years entered the study. An oral tyramine screening test was conducted to select subjects sensitive to the tyramine pressor effect on systolic blood pressure (SBP) in the dose range of 200-400 mg. Safinamide 300 mg was then administered once daily under fasting conditions. Starting on day 5 (safinamide pharmacokinetic steady state), single ascending doses of tyramine were co-administered daily: 50, 100 and 200 mg were administered on days 5, 6 and 7, respectively. Vital parameters were monitored by telemetry. No SBP increase ≥30 mmHg over baseline was observed when tyramine was co-administered with safinamide. Less than one third of the 400 mg responders reported SBP increases between 22 and 27 mmHg, which were below the threshold of 30 mmHg over baseline. SBP increases, as well as time interval to pressor response measured after co-treatment with safinamide and tyramine 200 mg, were not significantly different from those measured after administration of oral tyramine 200 mg alone. Safinamide 300 mg, administered o.d. under fasting conditions, does not change the tyramine pressor response as evaluated at steady state after 6-7 days of treatment as compared with the effect of tyramine administered alone. Safinamide, which inhibits monoamine oxidase (MAO)-B, does not affect oral tyramine metabolism mediated mostly by the intestinal MAO-A.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Use of a spacer minimizes oropharyngeal deposition and optimizes drug targeting to the airways in subjects with coordination difficulties. However, the increase in pulmonary deposition often observed with spacer devices, could potentially lead to an increase in overall systemic exposure.• EMA guidelines recommend that the development of a pMDI should always include testing of at least one specific spacer for use with a particular pMDI.• The aim of this study was to examine the effect of AeroChamber Plus™ on the lung bioavailability and total systemic exposure of a hydrofluoroalkane (HFA) pMDI fixed combination of extra‐fine beclometasone dipropionate/formoterol (100/6 µg) (Foster®).WHAT THIS STUDY ADDS• The use of AeroChamber Plus™ optimizes the lung delivery of beclometasone and formoterol in subjects that find it difficult to synchronize aerosol actuation with the inspiration of breath.• The total systemic exposure of beclometasone 17‐monopropionate and formoterol was not significantly increased by the use of the AeroChamber Plus™ spacer.• Use of the AeroChamber Plus™ spacer device with the extra‐fine beclometasone dipropionate/formoterol (100/6 µg) fixed combination pMDI can be a valuable option for certain patients groups, such as subjects with difficulties in achieving an adequate inhalation technique.AIM To assess the effect of AeroChamber Plus™ on lung deposition and systemic exposure to extra‐fine beclometasone dipropionate (BDP)/formoterol (100/6 µg) pMDI (Foster®). The lung deposition of the components of the combination given with the pMDI was also evaluated using the charcoal block technique.METHODS Twelve healthy male volunteers received four inhalations of extra‐fine BDP/formoterol (100/6 µg) using (i) pMDI alone, (ii) pMDI and AeroChamber Plus™ and (iii) pMDI and charcoal ingestion.RESULTS Compared with pMDI alone, use of AeroChamber Plus™ increased the peak plasma concentrations (Cmax) of BDP (2822.3 ± 1449.9 vs. 5454.9 ± 3197.1 pg ml−1), its active metabolite beclometasone 17‐monopropionate (17‐BMP) (771.6 ± 288.7 vs. 1138.9 ± 495.6 pg ml−1) and formoterol (38.4 ± 17.8 vs. 54.7 ± 20.0 pg ml−1). For 17‐BMP and formoterol, the AUC(0,30 min), indicative of lung deposition, was increased in the AeroChamber Plus™ group by 41% and 45%, respectively. This increase was mainly observed in subjects with inadequate inhalation technique. However, use of AeroChamber Plus™ did not increase the total systemic exposure to 17‐BMP and formoterol. Results after ingestion of charcoal confirmed that AUC(0,30 min) can be taken as an index of lung bioavailability and that more than 30% of the inhaled dose of extra‐fine BDP/formoterol 100/6 µg was delivered to the lung using the pMDI alone.CONCLUSIONS The use of AeroChamber Plus™ optimizes the delivery of BDP and formoterol to the lung in subjects with inadequate inhalation technique. The total systemic exposure was not increased, supporting the safety of extra‐fine BDP/formoterol pMDI with AeroChamber Plus™.