Abstract
The indirect effect of diet on the single-and multiple-dose pharmacokinetics of sustained-release ketoprofen was studied in 16 healthy male volunteers. In an open, cross-over design, 200 mg ketoprofen was administered as a gastric-juice-resistant, sustained-release tablet once daily during two periods of 5 days. A low-calorie/low-fat diet (LCFD) was given in the first period and a high-calorie/high-fat diet (HCFD) in the second period. The first meal on each day was given 4 h after drug intake. Ketoprofen plasma concentrations were measured over 24 h after the first dose on day 1 and over 36 h after the final dose on day 5 of each period.
On average, plasma concentrations of ketoprofen were higher with the LCFD than with the HCFD. With the HCFD there was a tendency to longer absorption-lag times on day 5. The maximum concentration and the area under the curve over one 24-h dosage period (AUC0–24) were significantly higher with the LCFD, both on day 1 and on day 5. For AUC0–24 the differences were on average 15% (day 1) and 24% (day 5). The same tendency was observed for the amount excreted in urine over 24 h (Ae), but the difference was only significant on day 1 (14%). The elimination rate constant (Kβ) and the mean residence time were similar for the two diets, both on day 1 and on day 5.
From these results, we conclude that there was an acute indirect effect of diet when a meal was had 4 h after intake of the medication. This resulted in a greater extent of ketoprofen absorption with the LCFD than with the HCFD. The absorption rate was apparently not influenced by this acute effect. The longer gastric residence time of ketoprofen with the HCFD may be the result of a long-term indirect effect on gastric emptying rate. If the extreme difference between the diets in this study is taken into account, it seems unlikely that the observed indirect effects have implications for clinical practice.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Cathcart BJ, Vince JD, Gordon AJ, Bell MA, Chalmers IM (1973) Studies on 2-(3-benzoylphenyl) propionic acid (Orudis). A double-blind crossover trial in patients with rheumatoid arthritis and an assessment of its influence on hepatic drug-metabolizing enzymes. Ann Rheum Dis 32: 62–65
Mitchell WS, Scott P, Kennedy AC, Jeffries MG, Brooks PM, Templeton R (1975) Clinico-pharmacological studies on ketoprofen (Órudis). Curr Med Res Opin 3: 423–430
Huskisson EC, Woolf DL, Balme HW, Scott J, Franklin S (1976) Four new anti-inflammatory drugs: responses and variations. Br Med J 1: 1048–1049
Mills SB, Bloch M, Bruckner FE (1973) Double-blind cross-over study of ketoprofen and ibuprofen in management of rheumatoid arthritis. Br Med J 4: 82–84
Yang CS, You JSH (1988) Dietary effects on drug metabolism by the mixed-function oxidase system. Pharmacol Ther 38: 53–72
Welling PG (1977) Influence of food and diet on gastrointestinal drug absorption: review. J Pharmacokinet Biopharm 5: 291–334
Anderson KE (1988) Influence of diet and nutrition on clinical pharmacokinetics. Clin Pharmacokinet 14: 325–346
Kappas A, Anderson KE, Conney AH, Alvares AP (1976) Influence of dietary protein and carbohydrate on antipyrine and theophylline metabolism in man. Clin Pharmacol Ther 20: 643–653
Cernish SM, Rubin A, Rodda BE, Ridolfo AS, Gruber CM Jr. (1972) The physiological disposition of fenoprofen in man. J Med 3: 249–257
Lewis JR (1975) Evaluation of ibuprofen (Motrin) A new antirheumatic agent. JAMA 233: 364–365
Tamassia V, Corvi G, Moro E, Tosolini GP, Fuccella LM (1977) Effect of food on the absorption of indoprofen administered orally to man in two dosage forms. Int J. Clin Pharmacol Res 15: 389–393
Bannier A, Brazier JL, Ribon B, Quincy C (1980) Determination of ketoprofen in biological fluids by reversed-phase chromatography J Pharm Sci 69: 763–765
Gibaldi M, Perrier D (1982) Pharmacokinetics, 2nd edn, Marcel Dekker, New York
Deleted
Steinijans VW (1990) Pharmacokinetic characterization of controlled release formu-lations. Eur J Drug Metab Pharmacokinet 15: 173–181
Jaffe JM, Colaizzi JL, Barry H (1970) Effects of dietary components on gastro-intestinal absorption of acetaminophen in man. J Pharm Sci 60: 1646–1650
Welling PG, Lyons LL, Craig WA, Trochta GA (1975) Influence of dietary fluid on bioavailability of theophylline. Clin Pharmacol Ther 17: 475–480
Bogentoft C, Carlsson I, Ekenved G, Magnusson A (1978) Influence of food on the absorption of acetylsalicylic acid from enteric-coated dosage forms. Eur J Clin Pharmacol 14: 351–355
Blythe RH, Grass GM, MacDonnell DR (1959) The formulation and evaluation of enteric coated aspirin tablets. Am J Pharmacol 34: 206–216
Willis JV, Jack DB, Kendall MJ, John UA (1981) The influence of food on the absorption of diclofenac as determined by the urinary excretion of the unchanged drug and its major metabolites during chronic administration. Eur J Clin Pharmacol 19: 39–44
Willis JV, Kendall MJ, Jack DB (1981) The influence of food on the absorption of diclofenac after single and multiple oral doses. Eur J Clin Pharmacol 19: 33–37
Willis RJ, Velagapudi RV, Puri SK, Yakatan GJ (1985) The effect of food and antacid on the absorption of fendosal. Biopharm Drug Dispos 6: 43–50
Von Schrader HW, Bucher G, Dierdorf D, Mugge H, Wolf D (1983) Nabumetone — a novel antiinflammatory drug: the influence of food, milk, antacids and analgesics on bioavailability of single oral doses. Int J Clin Pharmacol Ther Toxicol 21: 311–321
Nilsen OG, Wessel-Ass T, Walseth F (1985) Single dose pharmacokinetics of tiaprofenic acid. Effects of food and severe renal insufficiency. Arzneimittelforschung/Drug Res 35/5: 871–875
Read NW, Miles CA, Fisher D, Holgate AM, Kime ND, Mitchell MA, Reeve AM, Roche TB, Walker M (1980) 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
Cummings JH, Jenkins DJA, Wiggins HS (1976) Measurement of the mean transit time of dietary residue through the human gut. Gut 17: 210–218
Metcalf AM, Phillips SF, Zinsmeister AR, MacCarty RL, Beart RW, Wolff BG (1987) Simplified assessment of segmental colonic transit. Gastroenterology 92: 40–47
Ryan JP, Bojwani A (1986) Effect of ovariectomy and sex steroid hormone pretreatment on colonic transit in the rat. Am J Physiol 251 [Gastronitest Liver Physiol 14]: G46-G50
Kamm MA, Farthing MJG, Lennard-Jones JE (1989) Bowel function and transit rate during the menstrual cycle. Gut 30: 605–608
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Le Liboux, A., Frydman, A., Oosterhuis, B. et al. Effect of diet on the single- and multiple-dose pharmacokinetics of sustained-release ketoprofen. Eur J Clin Pharmacol 47, 361–366 (1994). https://doi.org/10.1007/BF00191169
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00191169