RESUMEN
ColoPulse tablets are an innovative development in the field of oral drug delivery and are characterized by a colon-specific release. Until now ColoPulse dosage forms (only capsules) have been studied in healthy volunteers having a standardized breakfast three hours after administration but not in specific patient groups and not with a shorter interval between administration and breakfast. Information on bioavailability and release characteristics of ColoPulse tablets in Crohn's patients and the influence of food and time of food intake is a prerequisite to properly design future clinical studies with active substances in these patients. In the current cross-over study bioavailability and drug release characteristics of ColoPulse tablets were compared in healthy volunteers and in Crohn's patients in remission. Furthermore the influence of food and time of food intake on the in vivo drug release behavior of ColoPulse tablets was investigated. In this study the dual label isotope strategy was used which means that a ColoPulse tablet containing (13)C-urea and an uncoated, immediate release tablet containing (15)N2-urea were taken simultaneously. Breath and urine samples were collected during the test day for isotope analysis. The appearance of the stable isotopes in breath and/or urine provides information on the site of release from the dosage form, release characteristics and bioavailability. Both tablets were administered on two different days in a cross-over design: the first day with a breakfast (non-standardized) one hour after administration and the second day with a standardized breakfast three hours after administration of the tablets. There was no difference in instructions for administration between both days. Results of 16 healthy volunteers and 14 Crohn's patients were evaluated. At least 86% (51 out of 59) of all ColoPulse tablets administered in this study released their contents at the desired intestinal region. There was no significant difference in bioavailability between healthy volunteers and Crohn's patients on both days (day 1 75.8% vs 90.2%, p=0.070 and day 2 83.4% vs 91.4%, p=0.265). There was also no significant influence of food and time of food intake on bioavailability in healthy volunteers (75.8% and 83.4%, p=0.077) and in Crohn's patients (90.2% and 91.4%, p=0.618) when day 1 and day 2 were compared. Release characteristics did not significantly differ between healthy volunteers and Crohn's patients. However, food and time of food intake had some, clinically non-relevant, influence on the release characteristics within both groups which is in line with the fact that food affects gastro-intestinal transit times. This study shows that ColoPulse tablets enable the site-specific delivery of drugs or other compounds (e.g. diagnostics) deep in the ileo-colonic region of the intestine of Crohn's patients in a comparable amount and rate as in healthy volunteers. Food and time of food intake had no relevant influence on bioavailability. In conclusion ColoPulse delivery systems are promising and deserve further research for local therapy with immunosuppressive drugs in Crohn's patients in the near future.
Asunto(s)
Enfermedad de Crohn/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Urea/administración & dosificación , Administración Oral , Adolescente , Adulto , Disponibilidad Biológica , Colon/metabolismo , Estudios Cruzados , Preparaciones de Acción Retardada/química , Ingestión de Alimentos , Femenino , Alimentos , Humanos , Íleon/metabolismo , Masculino , Persona de Mediana Edad , Comprimidos Recubiertos , Urea/farmacocinética , Adulto JovenRESUMEN
OBJECTIVE: Long-chain polyunsaturated omega-3 fatty acids (LCPomega3) synthesis, notably that of docosahexaenoic acid (DHA), from the precursor alpha-linolenic acid (ALA) proceeds with difficulty. We investigated whether carnitine supplementation augments the LCPomega3 status of apparently healthy vegans and lacto-ovo-vegetarians, who are expected to have low carnitine status. METHODS: Group A (n = 11) took 990 mg/day l-carnitine from weeks 1-4, and 990 mg/day l-carnitine + 4 mL/day linseed oil from weeks 5-8. Group B (n = 9) took 4 mL/day linseed oil from weeks 1-4, and 4 mL/day linseed oil + 990 mg/day l-carnitine from weeks 5-8. Fatty acid compositions of red blood cells, platelets, plasma cholesterol esters and plasma triglycerides were measured in the fasting state at baseline, and after 4 and 8 weeks. RESULTS: Carnitine supplementation increased plasma free and total carnitine concentrations with 30 and 25%, respectively, but did not affect eicosapentaenoic acid (EPA) and DHA contents of any of the investigated compartments. EPA and DHA changes were negatively related to initial carnitine status. CONCLUSIONS: Our results suggest that carnitine is not an important limiting factor, if any, for LCPomega3 synthesis in vegans and lacto-ovo-vegetarians. This conclusion is also likely to apply to omnivores. The most efficient means to augment EPA and particularly DHA status remains consumption of LCPomega3 from e.g. fish or supplements.