Abstract
Purpose. To determine the bioavailability and pharmacokinetic profile of lumiracoxib from different sites in the gastrointestinal tract.
Methods. Subjects (11 healthy adult males) were randomized to receive a 100 mg lumiracoxib dose, via a site-specific radiolabeled delivery capsule, to the stomach (internal reference), proximal small bowel, distal small bowel, or ascending colon. Gamma scintigraphy was used for real-time visualization of capsule location, and a radio- frequency signal was used to activate capsules at target site.
Results. Ten subjects completed the study. The mean capsule activation times for the stomach, proximal small bowel, distal small bowel, and ascending colon were 0.22, 1.52, 3.43, and 11.46 h post dose, respectively. Lumiracoxib was well absorbed from the proximal and distal small bowel, with AUC0-≈ ratios 104% (86, 127)% and 110% (89, 136)%, respectively. The highest Cmax (2413 ng/ml) and AUC0-≈ for lumiracoxib were in the distal small bowel (6842 ng·h/ml). Effective absorption was observed from the ascending colon, with an AUC0-≈ ratio of 85% (69, 104)% vs. the reference.
Conclusions. Lumiracoxib is rapidly and efficiently absorbed throughout the gastrointestinal tract.
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References
D. V. Prior, A. L. Connor, and I. R. Wilding. Human drug absorption in early development. Applications of Pharmacokinetic Principles in Drug Development. Kluwer Academic/Plenum Publishers, New York, 2003.
I. R. Wilding. The Enterion capsule: a novel technology for understanding the biopharmaceutical complexity of new molecular entities (NMEs). Drug Del. Tech 1:50-52 (2001).
L. Knutson, B. Odlind, and R. Hullgren. A new technique for segmental jejunal perfusion in man. Am. J. Gastroenterol. 84:1278-1284 (1989).
N. W. Read, M. N. Al Janabi, T. E. Bates, and D. C. Barber. Effect of gastrointestinal intubation on the passage of a solid meal through the stomach and small intestine in humans. Gastroenterology. 84:1568-1572 (1983).
I. R. Wilding, P. H. Hirst, and A. L. Connor. Development of a new clever engineering-based capsule for human drug absorption studied. Pharm. Sci. Tech. Today 3:385-392 (2000).
A. L. Connor, H. A. Wray, B. Voith, U. Voigt, J. Nagelschmitz, J. Kuhlmann, and I. R. Wilding. Using the Enterion capsule to investigate the absorption of faropenem daloxate delivered in particulate form from different sites of the Gastrointestinal Tract. Pharm. Sci. 3(3) (2001).
P. J. Marshall, C. Berry, J. Wasvary, J. V. Duzer, Z. Du, G. Scott, C. Rordorf, S. Milosavljev, and R. A. Fujlmoto. The in vitro and in vivo selectivity of COX189, a new and highly selective inhibitor of COX-2. Ann. Rheum. Dis. 61(Suppl. 1):259(Abstract SAT0013) (2002).
J. B. Mangold, H. Gu, L. C. Rodriguez, G. Scott, J. Bonner, and C. Rordorf. Pharmacokinetics and metabolism of lumiracoxib in healthy male subjects. Drug Metab. Rev. 34(Suppl. 1):141(Abstract 281) (2002).
Data on file. Novartis Pharma AG, Basel, Switzerland.
G. Scott, C. Rordorf, P. Blood, J. Branson, S. Milosavljev, and G. Greig. Dose escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of COX189 in healthy subjects. Ann. Rheum. Dis. 61(Suppl. 1):242(Abstract FR1300) (2002).
T. J. Schnitzer, P. Geusens, P. Hasler, S. K. Patel, G. Poor, I. Senftleber, S. Jayawardene, V. S. Sloan, R. S. Macerata. Efficacy and safety of COX189 in osteoarthritis: a multi-national study. Arthritis Rheum. 43(Suppl. 9):1616(Abstract S336) (2000).
C.J. Hawkey, PUCCINI (prevention of ulcers with COX189 compared with ibuprofen in NSAID investigation) Group. Reduced cumulative incidence of gastroduodenal ulcers with two doses of a new coxib, COX189 compared with standard therapeutic doses of ibuprofen in osteoarthritis patients. Gastroenterology. 122(4):(Suppl.1):A-345(Abstract M1732) (2002).
D. F. Evans, G. Pye, R. Bramley, A. G. Clark, T. J. Dyson, and J. D. Hardcastle. Measurement of gastrointestinal pH profiles in normal ambulant human subjects. Gut 29:1035-1041 (1988).
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Wilding, I.R., Connor, A.L., Carpenter, P. et al. Assessment of Lumiracoxib Bioavailability from Targeted Sites in the Human Intestine Using Remotely Activated Capsules and Gamma Scintigraphy. Pharm Res 21, 443–446 (2004). https://doi.org/10.1023/B:PHAM.0000019297.07378.bd
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DOI: https://doi.org/10.1023/B:PHAM.0000019297.07378.bd