Tetracycline absorption

There are problems as well in the absorption of certain drugs in the presence of specific food components. L-Dopa absorption may be inhibited in the presence of certain amino acids formed from the digestion of proteins [43], The absorption of tetracycline is reduced by calcium salts present in dairy foods and by several other cations, including magnesium and aluminum [115-117], which are often present in antacid preparations. In addition, iron and zinc have been shown to reduce tetracycline absorption [118], Figure 17 illustrates several of these interactions. These cations react with tetracycline to form a water-in-soluble and nonabsorbable complex. Obviously, these offending materials should not be co-administered with tetracycline antibiotics. 

PA Kramer, DJ Chapron, J Benson, SA Merik. Tetracycline absorption in elderly patients with achlorhydria. Clin Pharmacol Ther 23 467-472, 1978. 

Table 2 Correlation of Dissolution Rates with Biological Measurements for Tolbutamide and Tetracycline Absorption in Humans... 

E. Nelson, Influence of dissolution rate and surface on tetracycline absorption, J. Am. Pharm. Assoc. Sci. Ed., 48, 96-103 (1959). 

Tetracyclines Absorption (%) max (mcg/mL) 1"niax Protein binding (%) Serum half-life (h)... 

Absorption from the gastrointestinal tract can be affected by other drugs and by food. Aluminum, calcium, and magnesium ions in antacids or dairy products form insoluble chelates with all tetracyclines and inhibit their absorption. Food inhibits tetracycline absorption but enhances doxycycline absorption food delays but does not diminish metronidazole absorption fatty food enhances griseofulvin absorption. 

The administration of tetracycline with food can ameliorate its irritative effects, bnt food can adversely affect the drug s absorption. In contrast, the absorption of doxycycline is only slightly affected by the presence of food, including dairy prodncts. Becanse all tetracyclines can form complexes with divalent cations, the absorption of any tetracycline is markedly decreased when administered with iron-containing tonics or antacids containing calcium, magnesium, or aluminum. Sodium bicarbonate also adversely affects tetracycline absorption. 

Allen LV, Levinson RS, Robinson C, Lau A. Effect of surfactant on tetracycline absorption across everted rat intestine. J Pharm Sci 1981 70 269-271. 

Sodium bicarbonate 2 g reduced the absorption of a 250-mg capsule of tetracycline by 50% in 8 subjects. If however tetracycline was dissolved before administration, the absorption was unaffected by the sodium bicarbonate. Another study stated that sodium bicarbonate 2 g had an insignificant effect on tetracycline absorption. ... 

Barr WH, Adir J, Garrettson L. Decrease of tetracycline absorption in man by sodium bicarbonate. Clin Pharmacol Ther ( 97 ) 12, 779-84. 

Cole JJ, Charles BG, Ravenscroft PJ. Interaction of cimetidine with tetracycline absorption. Lancet( 9S0) ii, 536. 

Quinapril, formulated as Accupro also contains magnesium carbonate (250 mg in a 40 mg quinapril capsule, 47 mg in a 5 mg capsule). A pharmacokinetic study in 12 healthy subjects investigating the potential interaction between the magnesium carbonate in these capsules and tetracycline found that single doses of both of these formulations of quinapril markedly reduced the tetracycline absorption. The 5 mg and 40 mg quinapril capsules reduced the tetracycline AUC by 28% and 37%, respectively, and the maximum serum levels were reduced by 25% and 34%, respectively. ... 

This study was repeated with doxycycline 200 mg and zine, but doxycy-cline absorption was not affected. A reduction in tetracycline absorption of more than 50% has been seen in other studies when zine was given eon-eurrently. ... 

Andersson K-E, Bratt L, Dencker H, Kamme C, Lanner E. Inhibition of tetracycline absorption by zinc, EurJ Clin Pharmacol (1976) 10, 59-62. 

Mapp RK, McCarthy TJ, The effect of zinc sulphate and of bicitropeptide on tetracycline absorption, SAfrMedJ 916) 50, 1829-30,... 

The tetracyclines are a group of antibiotics with the same basic chemical structure they are derivatives of the naphthacene ring system. Compounds of the series differ in the composition of the side chains (Fig. 1). These antibiotics derived from different Streptomyces species show closely related spectra of bacteriostatic properties, with the exception of minocycline, which is very effective against most Staphylococcus strains resistant to other tetracyclines. Absorption, metabolism, and excretion of the different tetracyclines vary, however. After oral application, tetracycline, oxytetracycline, and chlortetracycline are absorbed to a much lesser degree than demethylchlortetracycline, methacycline, or the almost entirely absorbed minocycline. Maximum blood levels are found 2-6 h after oral intake and immediately in the case of intravenous infusion. Half-lives between 8 and 15 h were reported. The tetracyclines diffuse readily across the vascular barrier and are found in various tissues such as the liver, spleen, bone marrow, kidney, skin, and lungs as well as the peritoneal and pericardiac cavities. The tetracyclines are also able to... 

Each tetracycline possesses a characteristic uv-absorption spectmm and this property is used extensively in stmcture elucidation (12,13). This spectmm results from the contribution of two chromophores the BCD ring system gives a X at approximately 350 nm and the A-ring a X at... 

There is an increased risk of toxicity of MTX when administered with the NSAIDs, salicylates, oral antidiabetic drugs, phenytoin, tetracycline, and probenecid. There is an additive bone marrow depressant effect when administered with other drug known to depress the bone marrow or with radiation therapy. There is an increased risk for nephrotoxicity when MTX is administered with other drug that cause nephrotoxicity. When penicillamine is administered with digoxin, decreased blood levels of digoxin may occur. There is a decreased absorption of penicillamine when the dmg is administered with food, iron preparations, and antacids. 

The absorption of oral iron is decreased when tlie agent is administered with antacids, tetracyclines, penicillamine, and the fluoroquinolones. When iron is administered with levothyroxine, there may be a decrease in tlie effectiveness of levothyroxine When administered orally, iron deceases the absoqition of lev-odopa. Ascorbic acid increases tlie absoqition of oral iron. Iron dextran administered concurrently with chloramphenicol increases serum iron levels. 

The effects of metoclopramide are antagonized by concurrent administration of anticholinergics or narcotic analgesics. Metoclopramide may decrease the absorption of digoxin and cimetidine and increase absorption of acetaminophen, tetracyclines, and levodopa Metoclopramide may alter die body s insulin requirements. 

Oral administration of bicarbonate may decrease the absorption of ketoconazole. Increased blood levels of quinidine, flecainide, or sympatiiomimetics may occur when these agents are administered with bicarbonate There is an increased risk of crystalluria when bicarbonate is administered with the fluoroquinolones. Fbssible decreased effects of lithium, methotrexate, chlorpropamide, salicylates, and tetracyclines may occur when these drag s are administered with sodium bicarbonate. Sodium bicarbonate is not administered within 2 hours of enteric-coated drugs the protective enteric coating may disintegrate before the drug reaches the intestine. 

Common adverse effects of calcium salts include constipation, bloating, cramps, and flatulence. Changing to a different salt form may alleviate symptoms for some patients. Calcium salts may reduce the absorption of levothyroxine, iron and some antibiotics, such as tetracycline and fluoroquinolones. 

Absorption of antimicrobial agents such as fluoroquinolones and tetracyclines that can be bound by divalent and trivalent cations potentially could be compromised by administration with EN formulas containing these cations. The fluoroquinolones (e.g., levofloxacin and ciprofloxacin) have been best studied in this regard, and results of studies are not consistent. Mechanisms for an interaction between fluoroquinolones and EN formulas other than chelation by cations have been postulated.40 Some institutions hold tube feedings for 30 to 60 minutes or more before and after enteral dosages of fluoroquinolones. Because ciprofloxacin absorption has been shown to be decreased with jejunal administration, this drug probably should not be given by jejunal tube.41... 

PJ Neuvonen, H Turakka. Inhibitory effect of various iron salts on the absorption of tetracycline in man. Eur J Clin Pharmacol 7 357-360, 1974. 

HR Ochs, DJ Greenblatt, HJ Dengler. Absorption of oral tetracycline in patients with Billroth-II gastrectomy. J Pharmacokinet Biopharm 6 295-303, 1978. 

As indicated, the ionized form of a drug will be more soluble than the nonionized form in the aqueous fluids of the GIT. The classic studies on the beneficial effects of changing nonionized drugs into salt forms were reported by Nelson for tetracycline [25], and Nelson et al. for tolbutamide [26]. Table 2 combines portions of the data from each study. Urinary excretion of the drug or its metabolite was taken as the in vivo measure of the relative absorption rate for the salt and the nonionized... 

Reduced absorption due to complex formation or other interactions between drugs and intestinal components leading to poor absorption has been described in a few cases. One example is the precipitation of cationic drugs as very poorly-soluble salts with bile acids, which has been reported for several compounds [62], Another well-known example is the complex formation between tetracycline together with calcium due to chelation after administration of the drug together... 

Two identification tests for oxytetracycline hydrochloride are given in the USP 28 [1], one being an ultraviolet absorption test and the other a color test. European Pharmacopoeia [2], British Pharmacopoeia (BP) 2003 [4], International Pharmacopoeia [5], and Pharmacopoeia of the People s Republic of China [6] described a thin-layer chromatography and color tests for identification of oxytetracycline hydrochloride and oxytetracycline dihydrate. For identification of oxytetracycline calcium, USP 28 [1] used Method II under identification of tetracycline <193>, whilst BP 2003 [4] described a TLC, color test, and calcium test as the method of identification. 

UV detection, diode-array detector (DAD) and fluorescence have been the detection techniques used, coupled to HPLC for the analysis of OTC. UV detection is set at 355 nm [49-51], 350 nm [40], or at 353 nm [52], Using the diode array detector [49] offers advantages that the target peak can be identified by its retention time and absorption spectrum. Compared to UV detection, fluorescence detection is generally more specific and is less interfered by other compounds in the sample matrix [51]. A HPLC method with electrochemical detection has also been suggested recently. Zhao et al. [53] described HPLC with a coulometric electrode array system for the analysis of OTC, TC, CTC, DC, and methacycline (MC) in ovine milk. An amper-ometric detection coupled with HPLC was developed by Kazemifard and Moore [54] for the determination of tetracyclines in pharmaceutical formulations. 

Chemical drug interactions result when two administered substances combine with each other chemically Tetracyclines complex with Ca (in milk), with aluminum (Al) and magnesium (Mg) (often components of antacids), and with Fe (in some multiple vitamins) to reduce the absorption of the tetracycline antibiotic. 

---