Pharmacokinetic Properties of Ibuprofen (IBU) From the Fixed-Dose Combination IBU/Caffeine (400/100 mg; FDC) in Comparison With 400 mg IBU as Acid or Lysinate Under Fasted and Fed Conditions-Data From 2 Single-Center, Single-Dose, Randomized Crossover Studies in Healthy Volunteers.

Rapid onset of analgesic action is linked with rapid absorption of analgesics (high maximum concentration [Cmax ] and short time to maximum concentration [tmax ]). After overnight fasting, ibuprofen lysinate reaches higher peak plasma levels (Cmax ) earlier than ibuprofen acid (tmax ) with comparable exposure (area under the plasma concentration-time curve [AUC]); however, subjects usually take ibuprofen with or within a short time of a meal. Therefore, pharmacokinetic (PK) studies under fed conditions may better characterize properties under real-life conditions. We investigated a new fixed-dose combination (FDC) of ibuprofen acid 400 mg and caffeine 100 mg in 2 single-dose, randomized, crossover PK studies in healthy subjects (both N = 36). The FDC was compared with ibuprofen 400 mg as acid and as lysinate after an overnight fast in Study 1, and with ibuprofen lysinate after a meal in Study 2. After fasting, results for ibuprofen in the FDC were comparable with those from ibuprofen acid alone. Caffeine did not affect the Cmax , tmax , and AUC. As expected, a higher Cmax and shorter tmax were observed with ibuprofen lysinates vs the FDC. Compared with administration after fasting, Cmax and tmax for ibuprofen lysinate administered postprandially were markedly different, while with FDC, these parameters were less sensitive to food intake. Taken after a meal, ibuprofen in the FDC reached tmax earlier than ibuprofen lysinate (median 1.25 vs 1.63 hours), and Cmax was approximately 13% higher, with comparable AUC, suggesting that the profile of ibuprofen was in favor of the FDC compared with ibuprofen lysinate. Thus, under real-life conditions, ibuprofen lysinate had no PK advantage over the FDC. All preparations were well tolerated.

Pathophysiological Factors in the Relationship between Chronological Age and Calculated Lung Age as Detected in a Screening Setting in Community-Dwelling Subjects.

AIM: To explore the relationship between pathophysiological factors and premature lung aging in a cohort of community-dwelling subjects in a health-screening setting. METHODS: 16,107 pharmacy customers in Germany (5954 males, 10,153 females; mean age 59.7 years) participated in a lung function screening project by providing demographic data, including smoking status and known airway conditions and performing spirometry with a Vitalograph, a spirometry screening device. Lung age was calculated from the spirometric findings, and the difference between chronological age and calculated lung age was analyzed in its relationship to the demographic data in general linear models. RESULTS: In the overall cohort, calculated lung age exceeded chronological age by 10.0 years. Based on the subset of non-smokers not reporting any airway conditions, Vitalograph data in this setting may underestimate FEV1 to some degree, but this apparently had little impact on the detection of association of lung age with pathophysiological factors or the corresponding effect sizes. The most important factors associated with greater lung age based on strength of association were presence of dyspnea, being a smoker, and reporting a history of COPD or asthma. Corresponding effect sizes for the difference between age and lung age were 6.5, 5.7, 13.9, and 8.3 years over the chronological age. DISCUSSION AND CONCLUSION: These data confirm the usefulness of screening devices of lung function testing for epidemiological but potentially also for pharmaco-epidemiological studies.

A comprehensive review of the pharmacodynamics, pharmacokinetics, and clinical effects of the neutral endopeptidase inhibitor racecadotril.

Racecadotril, via its active metabolite thiorphan, is an inhibitor of the enzyme neutral endopeptidase (NEP, EC 3.4.24.11), thereby increasing exposure to NEP substrates including enkephalins and atrial natriuretic peptide (ANP). Upon oral administration racecadotril is rapidly and effectively converted into the active metabolite thiorphan, which does not cross the blood-brain-barrier. Racecadotril has mainly been tested in animal models and patients of three therapeutic areas. As an analgesic the effects of racecadotril across animal models were inconsistent. In cardiovascular diseases such as hypertension or congestive heart failure results from animal studies were promising, probably related to increased exposure to ANP, but clinical results have not shown substantial therapeutic benefit over existing treatment options in cardiovascular disease. In contrast, racecadotril was consistently effective in animal models and patients with various forms of acute diarrhea by inhibiting pathologic (but not basal) secretion from the gut without changing gastro-intestinal transit time or motility. This included studies in both adults and children. In direct comparative studies with loperamide in adults and children, racecadotril was at least as effective but exhibited fewer adverse events in most studies, particularly less rebound constipation. Several guidelines recommend the use of racecadotril as addition to oral rehydration treatment in children with acute diarrhea.