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| Year : 1987 | Volume
: 33
| Issue : 3 | Page : 117-9 |
Effect of food on doxycycline absorption.
Kshirsagar NA, Ankalesaria PS
How to cite this article:
Kshirsagar N A, Ankalesaria P S. Effect of food on doxycycline absorption. J Postgrad Med 1987;33:117 |
The significance of food-drug interaction as a variable in bioavailability of drugs is now recognised. Food intake has been reported to increase the absorption of some drugs like sulphadimidine and griseofulvin while decreasing the absorption of others like penicillin and cephalexin.[6]
Food may influence drug absorption as a result of many factors such as gastric emptying time, hepatic blood flow or physical and chemical interaction between particular food components and the drug molecules. Different constituents of food have also been shown to affect drug absorption in varying ways.[3]
Tetracycline antibiotics are used for the treatment of a variety of infections. Doxycycline has the advantages of nearly complete absorption and long duration of action, and is therefore one of the most commonly used tetracyclines. As opposed to tetracycline, absorption of doxycycline is reported to be unaffected by food.[5] The present study was carried out to assess the effect of standard breakfast on doxycycline absorption.
The study was carried out in six healthy male volunteers aged between 19 and 21 years, body weight ranging from 54 to 63 kg, selected on the basis of normal clinical and routine biochemical investigations. Written informed consent was obtained. After overnight fasting, the subjects were given two doxycycline capsules 100 mg each, either on empty stomach or after a standard breakfast, no food being permitted for 2 hours after it. The standard breakfast consisted of bread, butter and a commercially available milk drink (instead of milk, for sake of uniformity); (K calories 508, proteins 15 gm, carbohydrates 72.5 gm and fat 17.5 gm). The order of administration of drug, with food or after fasting, was randomised and the cross over was done after a washout period of 1 week. Blood samples were collected at 0 hour and at 1, 2, 3, 4, 6, 8, 12 hours after drug administration.
Doxycycline content was estimated microbiologically[2] using test organism Bacillus cereus var mycoides ATCC 11778. The sensitivity of the method is 0.5 µg/ml.
Area under plasma time concentration curve, C-max, and T-max were the parameters used to assess the bioavailability of doxycycline.
Results are summarised in [Table 1]. Standard breakfast reduced the bioavailability of doxycycline as judged by AUC to and maximum concentration reached in plasma, although the rate of absorption as judged by time taken to reach maximum concentration was not affected. [Fig. 1] gives doxycycline concentrations at different timings after drug administration. At 4, 6 and 8 hours after drug administration doxycycline levels were significantly higher when the drug was given on an empty stomach as compared to when given with food.
In the present study, standard breakfast was observed to reduce doxycycline absorption significantly.
Absorption of tetracycline occurs in the stomach and the upper small intestine. Absorption of tetracyclines has been reported to be impaired by milk products, aluminum hydroxide gels, sodium bicarbonate, calcium and magnesium salts and iron preparations. The mechanisms responsible for decreased absorption appear to be chelation and an increase in gastric pH.[4]
Doxycycline has been reported to have less binding with ions such as calcium.[5] Schach von Wittenau[5] noted that doxycycline levels 1 hour after drug administration were lower when the drug was given after full breakfast as compared to when it was given on an empty stomach, though this was not statistically significant. At 3 hours and 12 hours after dosing, there was no difference between levels achieved after administration of drug on an empty stomach or with food.
In the present study, significant difference was observed in the plasma values determined 4, 6 and 8 hours after drug administration, AUC and C-max being also significantly lower after administration of drug with food. The infrequent sampling viz. 1, 2 and 12 hours after drug in the study by Schach von Wittenau[5] may be the reason for their missing the effect of food on doxycycline absorption.
Doxycycline undergoes enterohepatic circulation. Lower levels after food could be because of reduced absorption or reduced enterohepatic cycling.
In view of these results, it is advisable to instruct the patients to take doxycycline on an empty stomach.
This work has been supported by research grant No. HCS/DST/830/79 from Department of Science and Technology, Government of India, which is gratefully acknowledged. We wish to thank the Dean, Seth G. S. Medical College, Bombay, for permitting us to carry out this study.
| 1. | Gibaldi, M.: Pharmacokinetics of absorption and elimination of doxycycline in man. Chemotherapia, 12: 265-271, 1967.  |
| 2. | Grove, D. C. and Randall, W. A.: Assay methods of Antibiotics. A Laboratory Manual. Medical Encyclopedia Inc., New York, 1955, p. 50. |
| 3. | Kshirsagar, N. A., Takle, M. R., Nadkarni, P. M. and Satoskar, R. S.: Effect of standard breakfast and lunch on. sulphadimidine bioavailability. Ind. J. Med Res., 83: 618-622, 1986. |
| 4. | Sande, M. A. and Mandell, G. L.: Antimicrobial agents. In, Pharmacological microbial agents. In, "Pharmacological Basis of Therapeutics." Editors: A. G. Gilman, L. S. Goodman, T. W. Rall and F. Murad, 7th edition, MacMillan Publishing Co., New York, 1985, pp. 1170-1198. |
| 5. | Schach von Wittenau, M.: Some pharmacokinetic aspects of doxycycline metabolism in man. Chemotherapy, (Suppl.), 73:41-50, 1968. |
| 6. | Toothaker, R. D. and Welling, P. G.: The effect of food on drug bioavailability. Ann. Rev. Pharmacol. and Toxicol., 20:173-199, 1980. |
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