Summary
Absorption of single doses of Oxprenolol (80 mg) and of diclofenac-Na (100 mg) administered by colonoscopy into the cecum and the left flexure of the colon was compared with that after oral dosing in healthy volunteers. Plasma concentration/ time profiles of both drugs after oral and colonic dosing followed similar time courses. Oxprenolol reached maximal levels within 2 hours. Mean peak concentrations were lower after colonic compared with oral dosing. From the areas under the concentration-time curves (AUG) the relative bioavailability (BAVrel) was calculated. The mean BAVrel of Oxprenolol was 80% after colonic application versus oral administration. Oral and colonic administration of diclofenac-Na resulted in comparable peak plasma concentrations and AUCs. The apparent BAVrel of diclofenac-Na ranged from 50–110% with a mean of 80%.
The absorption of Oxprenolol delivered from an Oxprenolol OROS® 16/260 was studied in six patients with artificial stomata of the transversal colon. In the morning one Oxprenolol OROS® was introduced together with 20 ml water into the distal part of the stoma. Oxprenolol saliva and urinary concentrations were measurable in all patients.
The recovery of oral choquinol in urine and intestinal contents was studied in patients with a stoma of the terminal ileum or of the colon. The fecal recovery of the drug was highest in patients with ileostomy (90%) and lowest in those with colostomy (50%). The urinary recovery was correspondingly lowest in patients with ileostomy (10%) and highest in those with colostomy.
Drug absorption by the colonic mucosa can be investigated in patients with an intestinal stoma if no stenosis is present or in healthy volunteers after intracolonic administration during colonoscopy. Measuring saliva concentrations of lipophilic drugs with a constant ratio of saliva iplasma concentration may be sufficent for the first evaluation of pharmacokinetics in severely ill patients thus preventing unnecessary blood loss.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
R. Shields: Absorption from the human colon. In: Duthie H.L., Wormsley K.G., eds. Scientific basis of gastroenterology. Edinburgh, London and New York: Churchill-Livingstones, 398—414, (1979).
K.H. Antonin, P.R. Bieck, Ch. Schick, B. Steidle: Vergleichende chemische und radiologische Bestimmung der intestinalen Passagezeit (PZ) (Mund/Zoekum). 2. Gastroenterologie, 20, 554–555, (1982).
S.S. Davis, J.G. Hardy, J.W. Fara: Transit of pharmaceutical dosage forms through the small intestine. Gut, 27, 886–892, (1986).
J.H. Cummings, H.S. Wiggins: Transit through the gut measured by analysis of a single stool. Gut, 17, 219–223, (1976)
V.A. John, P.A. Shotton, J. Moppert, W. Theobald: Gastrointestinal transit of Oros drug delivery systems in healthy volunteers: a short report. Br. J. Clin. Pharmac., 19, 203S-206S, (1985)
N.W. Read, C.A. Miles, D. Fisher, A.M. Holgate, N.D. Kime, M.A. Mitchell, A.M. Reeve, T.B. Roche, M. Walker: Transit of a meal through the stomach, small intestine, and colon in normal subjects and its role in the pathogenesis of diarrhea. Gastroenterology, 79, 1276–1282, (1980).
F. Theeuwes: Novel drug delivery systems. In Drug absorption: Proceedings of the Edinburgh International Conference, eds Prescott L.F. and Nimmo W.S.ADIS Press, Hong Kong, 157—176, (1981).
J. Urquhart: Rate-controlled drug dosage. Drugs, 23, 207–222, (1982).
P.R. Bieck: Arzneistoffresorption aus dem menschlichen Dickdarm — neue Erkenntnisse. Acta Pharm. Technol, 33, 109–114 (1987).
K.H. Antonin, P.R. Bieck, M. Scheurlen, M. Jedrychowski, H. Malchow: Oxprenolol absorption in man after single bolus dosing into two segments of the colon compared with that after oral dosing. Br.J. Clin. Pharmacol, 19, 137S-142S, (1985).
K.H. Antonin, U. Wiest, P.R. Bieck: Colonic absorption of Oxprenolol in man delivered by an oral osmotic delivery system (OROS®). Acta Pharmacol Toxicol, 59, (Suppl. V), 86, (1986).
C.H. Gleiter, C. Cremer, P. Bieck, N. Hengen, G. Kieninger, W. Schönleber: Nicht-invasive Untersuchung der Arzneistoffabsorption in verschiedenen Dünn- und Dickdarmbereichen. 2. Gastrenterologie, 22, 509, (1984).
C.H. Gleiter, K.H. Antonin, P. Bieck, J. Godbillon, W. Schönleber, H. Malchow: Colonoscopy in the investigation of drug absorption in healthy volunteers. Gastrointestinal Endoscopy, 31, 71–73,(1985).
P.H. Degen, W. Riess: Simplified method for the determination of Oxprenolol and other betareceptor blocking agents in biological fluids by gas-liquid chromatography. J. Chromatogr., 121, 72–75, (1976).
J. Godbillon, S. Gauron, J.P. Metayer: High performance liquid chromatographic determination of diclofenac and its mono-hydroxylated metabolites in biological fluids. J. Chromatogr. Biomed. Appl, 338, 151–159, (1985).
P.H. Degen, W. Schneider, P. Vuillard, U.P. Geiger, W. Riess: The determination of clioquinol in biological materials by extractive alkylation and gas-liquid chromatography. J. Chromatogr., 117, 407–413, (1976).
D.G. Colin-Jones, R. Cockel, K.F.R. Schiller: Current endoscopic practice in the United Kingdom. Clinics in Gastroenterology, 7, 775–786, (1978).
J.P. Griffin: Drug interactions occurring during absorption from the gastrointestinal tract. Parmac. Ther., 15, 79–88, (1981).
K.J. Breen, R.E. Bryant, J.D. Levinson, S. Schenker: Neomycin absorption in man. Studies of oral and enema administration and effect of intestinal ulceration. Ann. Int. Med., 76, 211—218, (1972).
P.C. Hawker, L.A. Turnberg. In: Alexander-Williams J., Binder H.J., eds.Large intestine, London: Butterworths 1–15, (1983).
A.G. De Boer, F. Moolenaar, L.G.J. De Leede, D.D. Breimer: Rectal drug administration: clinical pharmacokinetic considerations. Clin. Pharmacokin., 7, 285–311, (1982).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1987 Friedr. Vieweg & Sohn Verlagsgesellschaft mbH, Braunschweig
About this chapter
Cite this chapter
Antonin, KH., Bieck, P. (1987). Evaluation of the Colonic Drug Absorption in Patients with an Artificial Intestinal Stoma and by Colonoscopy in Normal Volunteers. In: Rietbrock, N., Woodcock, B.G., Staib, A.H., Loew, D. (eds) Drug Absorption at Different Regions of the Human Gastro-Intestinal Tract: Methods of Investigation and Results / Arzneimittelabsorption aus verschiedenen Bereichen des Gastrointestinaltraktes beim Menschen: Untersuchungsmethoden und Ergebnisse. Methods in Clinical Pharmacology, vol 7. Vieweg+Teubner Verlag, Wiesbaden. https://doi.org/10.1007/978-3-322-91091-2_6
Download citation
DOI: https://doi.org/10.1007/978-3-322-91091-2_6
Publisher Name: Vieweg+Teubner Verlag, Wiesbaden
Print ISBN: 978-3-528-07944-4
Online ISBN: 978-3-322-91091-2
eBook Packages: Springer Book Archive