Pharmacokinetics of levofloxacin after single intravenous and oral administration, and its interaction with sucralfate in mixed-breed dogs.

The study aims to establish the plasma pharmacokinetic parameters of levofloxacin in mixed-breed dogs, at a single dose of 5 mg/kg, intravenously, orally only and orally with sucralfate pre-treatment (1 g per animal), to evaluate its influence on antimicrobial absorption. Concentrations of levofloxacin in plasma were determined using high-performance liquid chromatography (HPLC) with fluorescence detection. After iv of levofloxacin, the mean (±SD) of AUC0-24, Vz, t½λz and MRT, was 19.05 ± 6.4 µg-h/ml, 2.43 ± 0.5 L/kg, 7.93 ± 1.41 hours and 8.7 ± 1.5 hours, respectively. After oral administration, the C max, t½λz and bioavailability were 1.95 ± 0.7 µg/ml, 7.65 ± 1.38 hours and 71.93 ± 9.75%, respectively. In animals given an oral dose of levofloxacin with sucralfate pre-treatment, there was a significant decrease (p < 0.05) in C max (0.57 ± 0.23 µg/ml), AUC (5.73 ± 2.26 µg-h/ml) and bioavailability (31.92 ± 14.19%). In the dogs studied, it is suggested that the dose 5 mg/kg of levofloxacin for both routes is inadequate to meet PK-PD targets for susceptible bacteria using breakpoints established by the Institute of Clinical and Laboratory Standards (CLSI).

Clinical Drug-Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs: Review and Perspectives.

Sucralfate, a complex of aluminium hydroxide with sulfated sucrose, forms a strong gastrointestinal tract (GIT) mucosal barrier with excellent anti-ulcer property. Because sucralfate does not undergo any significant oral absorption, sucralfate resides in the GIT for a considerable length of time. The unabsorbed sucralfate may alter the pharmacokinetics of the oral drugs by impeding its absorption and reducing the oral bioavailability. Because of the increased use of sucralfate, it was important to provide a reappraisal of the published clinical drug-drug interaction studies of sucralfate with scores of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along with study design, objectives and key remarks. While the loss of oral bioavailability was significant for the fluoroquinolone class, it generally varied for other classes of drugs, suggesting that impact of the co-administration of sucralfate is manageable in clinical situations. Given the technology advancement in formulation development, it may be in order feasible to develop appropriate formulation strategies to either avoid or minimize the absorption-related issues when co-administered with sucralfate. It is recommended that consideration of both in vitro and preclinical studies may be in order to gauge the level of interaction of a drug with sucralfate. Such data may aid in the development of appropriate strategies to navigate the co-administration of sucralfate with other drugs in this age of polypharmacy.

Effect of Sucralfate on the Relative Bioavailability of Enrofloxacin and Ciprofloxacin in Healthy Fed Dogs.

BACKGROUND: Sucralfate impairs absorption of ciprofloxacin and other fluoroquinolones in humans, but no sucralfate-fluoroquinolone interaction has been reported in dogs. Veterinary formularies recommend avoiding concurrent administration of these medications, which might impact compliance, therapeutic success, and resistance selection from fluoroquinolones. OBJECTIVES: To determine whether a drug interaction exists when sucralfate is administered to fed dogs concurrently with ciprofloxacin or enrofloxacin, and whether a 2 hour delay between fluoroquinolone and sucralfate affects fluoroquinolone absorption. ANIMALS: Five healthy Greyhounds housed in a research colony. METHODS: This was a randomized crossover study. Treatments included oral ciprofloxacin (C) or oral enrofloxacin (E) alone, each fluoroquinolone concurrently with an oral suspension of sucralfate (CS, ES), and sucralfate suspension 2 hours after each fluoroquinolone (C2S, E2S). Fluoroquinolone concentrations were evaluated using liquid chromatography with mass spectrometry. RESULTS: Drug exposure of ciprofloxacin was highly variable (AUC 5.52-22.47 h µg/mL) compared to enrofloxacin (AUC 3.86-7.50 h µg/mL). The mean relative bioavailability for ciprofloxacin and concurrent sucralfate was 48% (range 8-143%) compared to ciprofloxacin alone. Relative bioavailability of ciprofloxacin improved to 87% (range 37-333%) when sucralfate was delayed by 2 hours. By contrast, relative bioavailability for enrofloxacin and concurrent sucralfate was 104% (94-115%). CONCLUSIONS AND CLINICAL IMPORTANCE: A possible clinically relevant drug interaction for the relative bioavailability of ciprofloxacin with sucralfate was found. No significant difference in bioavailability was documented for enrofloxacin with sucralfate. Further research is warranted in fasted dogs and clinical cases requiring enrofloxacin or other approved fluoroquinolones in combination with sucralfate.

The effect of sucralfate tablets vs. suspension on oral doxycycline absorption in dogs.

The purpose of this study was to determine the effect of concurrent sucralfate (tablet or suspension) on doxycycline pharmacokinetics and to determine the effects of delaying sucralfate by 2 h on doxycycline absorption. Five dogs were included in a crossover study receiving: doxycycline alone; doxycycline concurrently with sucralfate tablet; doxycycline followed 2 h by sucralfate tablet; doxycycline concurrently with sucralfate suspension; and doxycycline followed 2 h by sucralfate suspension. Doxycycline plasma concentrations were evaluated with liquid chromatography with mass spectrometry. No interaction was seen when sucralfate was administered as a tablet. Sucralfate tablet fragments were frequently observed in some dogs' feces. The area under the curve (AUC) and maximum plasma concentration (CMAX ) were significantly lower (P < 0.001) in the concurrent sucralfate suspension group (AUC 7.2 h·µg/mL, CMAX 0.43 µg/mL) than with doxycycline alone (AUC 36.0 h·µg/mL, CMAX 2.53 µg/mL) resulting in a relative bioavailability of 20%. Delaying sucralfate suspension by 2 h after doxycycline administration resulted in no difference in doxycycline absorption as compared with doxycycline administration alone with a relative bioavailability of 74%. The lack of an interaction with sucralfate tablets suggests sucralfate should be administered as a suspension rather than tablet in dogs.

Effect of sucralfate on oral minocycline absorption in healthy dogs.

Sucralfate and minocycline may be administered concurrently to dogs. The relative bioavailability of tetracyclines may be reduced if administered with sucralfate, but studies confirming these interactions in dogs are not available. This study evaluated the pharmacokinetics of oral minocycline in dogs (M), determined the effects of concurrent administration of sucralfate and minocycline (MS) on minocycline pharmacokinetics, determined the effects of delaying sucralfate administration by 2 h (MS+2) on minocycline pharmacokinetics, and established dosing recommendations based on pharmacodynamic indices. Oral minocycline (300 mg) and sucralfate suspension (1 g) were administered to five greyhounds in a randomized crossover design. Minocycline plasma concentrations were evaluated using liquid chromatography with mass spectrometry. The maximum plasma concentration (CMAX ) and area under the curve (AUC) of minocycline were 1.15 µg/mL and 8.0 h* µg/mL, respectively. The CMAX and AUC were significantly lower (P < 0.05) in the MS group (CMAX  = 0.33 µg/mL, AUC 3.0 h*µg/mL) compared with M or MS+2 (CMAX = 0.97 µg/mL, AUC 10.3 h*µg/mL). Delaying sucralfate by 2 h did not decrease oral minocycline absorption, but concurrent administration significantly decreased minocycline absorption. A dose of 7.5 mg/kg p.o. q12 h achieves the pharmacodynamic index for a bacterial minimum inhibitory concentration (MIC) of 0.25 µg/mL (AUC:MIC≥33.9).

Effect of sucralfate on antibiotic therapy for Helicobacter pylori infection in mice.

It has been documented that sucralfate, a basic aluminum salt, enhances the efficacies of antibiotics against Helicobacter pylori, resulting in eradication rates comparable to those associated with the use of proton pump inhibitors. However, its mechanism of action remains unclear. The aim of the present study was to investigate sucralfate's ability to complement antibiotic treatment of H. pylori infection in vivo. Four weeks following induced H. pylori infection, clarithromycin (CAM) and amoxicillin (AMPC) were administered orally to C57BL/6 mice for 5 days, both with and without sucralfate or lansoprazole. When sucralfate was concurrently given with CAM and AMPC at the maximum noninhibitory doses for the treatment of H. pylori infection, the bacterial clearance rates were comparable to those achieved by treatment with lansoprazole plus those antibiotics. The results of pharmacokinetic studies showed that lansoprazole delayed gastric clearance and accelerated the absorption of CAM, whereas sucralfate suppressed both gastric clearance and absorption. AMPC was undetectable in all samples. Scanning electron microscopy with a microscope to which a energy dispersive spectrometer was attached revealed that aluminum-containing aggregated substances coated the mucosa surrounding H. pylori in mice receiving sucralfate plus antibiotics, whereas the gastric surface and pits where H. pylori had attached were clearly visible in mice receiving lansoprazole plus antibiotics. The addition of sucralfate to the antibiotic suspension resulted in a more viscous mixture that bound to the H. pylori-infected mucosa and that inhibited the loss of CAM bioavailability in the acidic environment. Sucralfate delays gastric clearance of CAM and physically captures H. pylori through the creation of an adherent mucus, which leads to bacterial clearance.

Radioterapia y tratamientos de soporte. Protección gastrointestinal. Antieméticos

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Comparative scintigraphic assessment of the intragastric distribution and residence of cholestyramine, Carbopol 934P and sucralfate.

It has been demonstrated that orally administered cholestyramine is distributed throughout the stomach and provides prolonged gastric residence via mucoadhesion. Gamma scintigraphy was used to compare the gastric emptying and residence of this resin with two formulations known to exhibit retentive or bioadhesive properties, Carbopol 934P and sucralfate. Fasted normal subjects received a single radiolabelled dose and gastrointestinal transit was monitored for 6 h. The subjects were fed after 4 h to determine the effects of inducing a fed pattern of motility on the retention of the formulations. Initial gastric emptying was similar (Mean T50+/-S.E.M.: cholestyramine=66.93+/-9.39 min; Carbopol=56.57+/-11.96 min; sucralfate=48.33+/-11.07 min; P=0.548: n=10), however, the emptying of cholestyramine slowed beyond 2 h. This resulted in greater residence for cholestyramine (Mean AUC0-6+/-S.E.M. (relative units)=11516+/-686 versus 7657+/-1170 versus 6170+/-998; cholestyramine versus Carbopol versus sucralfate; P=0.004: n=10), with approximately 25% remaining in the stomach at 6 h compared to 3.84 and 2.65% of Carbopol and sucralfate, respectively. Cholestyramine was also distributed widely throughout the stomach whereas Carbopol and sucralfate were concentrated in the body and antrum. Thus, as cholestyramine had a comparable emptying time to Carbopol and sucralfate but greater gastric residence and wider distribution, it could provide a potential mucoadhesive drug delivery system targeting the gastric mucosa for treatment of conditions such as Helicobacter pylori infection.

Study of interaction of gastrointestinal agents in the presence of cytoprotective drugs. Part II. In vitro study on the adsorption of selected spasmolytic drugs on sucralfate.

The subject of the research was the adsorption of selected musculotropic and cholinolytic spasmolytics on a cytoprotective drug--sucralfate. Adsorption evaluation was made by a static method, in vitro, the environment reaction, the concentrations of the tested drugs and the sucralfate form being taken into account. The obtained results prove that the analysed therapeutic substances are adsorbed on the sucralfate in all pH. The highest bonding capacity was observed in tests at pH=3.6, in the presence of sucralfate, which at this pH occurs in the form of suspension. The lowest capacity was at pH=1.5 in the presence of sucralfate in the paste form. In the group of the tested drugs, scopolamine butylbromide is adsorbed best, drotaverine hydrochloride little less and papaverine hydrochloride least of all.

Comparative mucoretention of sucralfate suspensions in an everted rat esophagus model.

A simple, rapid, and reproducible in vitro model was established to quantify the relative esophageal mucoadhesive properties of viscous liquid formulations, and the model was applied to compare marketed sucralfate suspensions (Gastrogel, Antepsin, and Ulcogant) to better understand differences in clinical performance. Rat esophageal mucosal segments were everted onto a glass rod and briefly immersed into a liquid formulation containing 51Cr microspheres. Indirect quantification of the retained formulation provided excellent recovery (98.7-101%) and reasonable precision (1.06-38.3% CV). Mucosal retention profiles of the formulations were determined by rinsing the coated tissue in relevant gastrointestinal fluids using the technique of reciprocating vertical immersion. Dispersions of the mucoadhesive hydrogel Carbopol 934P were employed to initially characterize the performance of the model with respect to composition of the rinse fluids, and type and amount of shear force during rinsing. Retention of Carbopol was sensitive to the mechanics of rinsing and to salivary salts but not mucin in the rinse medium. A sucralfate gel suspension (Gastrogel) showed much greater mucoadhesion and resistance to removal by saliva than two non-gel suspensions (Antepsin, Ulcogant). Results suggest that in situ gelation may be a contributing mechanism for strong esophageal retention. These in vitro results are in general agreement with published human esophageal retention data on similar sucralfate suspensions and lend credence to the everted rat esophagus as a qualitatively predictive in vitro model for development of esophageal mucoadhesive liquids.

Influence of intravenously administered ciprofloxacin on aerobic intestinal microflora and fecal drug levels when administered simultaneously with sucralfate.

Ciprofloxacin, when given intravenously (i.v.), is secreted in significant amounts via the mucosa into the intestinal lumen. Sucralfate inhibits the antimicrobial activity of ciprofloxacin. The effect of combined therapy on the intestinal flora was investigated in 16 healthy volunteers. They were randomly assigned to two groups. Group A received 2 g of sucralfate orally three times a day for 7 days and 400 mg of ciprofloxacin i.v. twice a day (b.i.d.) starting 3 days after the sucralfate administration began. Group B was given only 400 mg of ciprofloxacin i.v. b.i.d. for 4 days. A total of 9 stool samples were collected from each subject beginning the week before ciprofloxacin was administered and on days -1, 1, 2, 3, 4, 7, 9, and 10 or 11 after commencement of the infusion period. The aerobic fecal flora was determined by standard microbiological methods. Measurements of fecal ciprofloxacin levels were based on high-performance liquid chromatography. Counts of bacteria of the family Enterobacteriaceae decreased in all subjects and were below 10(2) CFU/g in eight of eight subjects (group A) and six of eight subjects (group B) on day 4, but they returned to normal in all but one subject (group A) 10 days after the last infusion. The decreases in levels of bacteria of the family Enterobacteriaceae were not significantly different in groups A and B (Kaplan-Meier test). Staphylococci and nonfermenters responded variably, enterococci and lactobacilli remained unchanged, and candida levels increased transiently in four subjects (two in each group). Maximum fecal drug levels ranged from 251 to 811 microg/g. No significant difference could be found between the two groups. The i.v. application of ciprofloxacin eliminates intestinal bacteria of the family Enterobacteriaceae in a rapid and selective manner. This effect is not affected by simultaneous oral application of sucralfate.

[Sucralfate in odontostomatology. Clinical experience]. / Il sucralfato in odontostomatologia. Nostra esperienza clinica.

BACKGROUND: We here describe the pharmacological and pharmacodynamic characteristics of the molecule sucralfate, the aluminum subsalt of sucrose-8-sulphate, introduced in Japan in 1968 as a mucoprotector for the treatment of peptic ulcers. For many years, attempts have been made to broaden the therapeutic indications of this molecule as has happened in oral medicine. This paper describes the results of the clinical trials reported in the international literature which were designed to investigate the use of sucralfate in the treatment of mucositis secondary to radio- and/or chemotherapy and during the course of recurrent aphtous stomatitis (RAS). METHODS: The authors carried out a pilot study with the aim of testing the efficacy and the tolerability of two formulations of sucralfate (20% suspension and 1 gram chewable tablets) in a total of 28 patients [14 with RAS: group A; and 14 with burning mouth syndrome (BMS): group B]. Each group was further divided into two subgroups [A1, A2, B1, B2] of 7 patients each. RESULTS: The results obtained in the RAS patients were encouraging, with an improvement in symptomatology in respectively 71.4% and 42.8% of the patients in subgroups A1 and A2; a number of authors have previously suggested that this is due to a primarily mucoprotective mechanism similar to that occurring in patients with peptic ulcer. The results were less favourable in the BMS patients: symptoms improved in respectively 42.8% and 28.6% of the patients in subgroups B1 and B2, but worsened in 28.6% and 28.6% in teh same subgroups. CONCLUSIONS: In conclusion we believe that sucralfate can be considered a valid therapeutic support in the context of the lenitive pharmacological protocols in which it is currently used, but our results do not allow a definitive judgement of its efficacy in patients with BMS.

Influence of topical rectal application of drugs on dextran sulfate-induced colitis in rats.

A rat model of colitis [dextran sulfate (DSS)] was used to study the permeation of Evans blue (EB) from the lumen into the wall of proximal and distal colonic loops after exposure to the dye for 2 hr. Topical application of drugs used in human ulcerative colitis (lidocaine, mesalazine, prednisolone, or sucralfate) was given daily during induction of colitis to protect the mucosa. The mucosal changes were evaluated with special regard to peptidergic innervation [substance P (SP) and neuropeptide Y (NPY)], invasion of antigen-presenting polydendritic cells, and mucin-containing goblet cells. DSS-treatment caused a significantly increased permeation of EB. In the proximal loops a significant inhibition was obtained after treatment with lidocaine, prednisolone, or sucralfate. In the distal loops only treatment with lidocaine had a preventive effect. Immunocytochemically there was a clear hyperplasia of both mucosal SP- and NPY-immunoreactive nerve fibers in regions with crypt abnormalities. In these regions also most of the goblet cells were devoid of mucus. Like the changes in permeation, these morphological changes were most prominent in the distal loops. With induction of colitis, the mucosa and lamina propria were invaded by polydendritic cells; the visual score was markedly decreased in the proximal loops treated with lidocaine, prednisolone, or sucralfate. In the distal loops similar effects were obtained after treatment with lidocaine or prednisolone. Prevention of the influx of antigens in both loops after lidocaine treatment with reduced recruitment of polydendritic cells into the lamina propria is suggested. The nerve hyperplasia may thus be secondary to luminal challenge with antigens during induction of colitis. The discrepancy between increased permeation and absence of polydendritic cell response in the distal loops after prednisolone may reflect separate actions of steroids on the intestinal epithelium and the immune cells.

Pharmacokinetic optimisation in the treatment of gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease (GORD) is a very common disorder of upper gastro-intestinal motility, differing widely in severity and prognosis. Medical therapy of GORD has involved antacids, alginates, prokinetic agents and antisecretory compounds, primarily H2 receptor antagonists and proton pump inhibitors. Knowledge of the pharmacokinetics of these compounds is important, to optimise the therapeutic benefit in each patient. GORD patients are often elderly and pharmacokinetics are move variable in this group. Furthermore, they often suffer from other diseases needing medical therapy and may need a combination of drugs to heal reflux oesophagitis and relieve reflux symptoms. The ideal therapy for GORD will have linear pharmacokinetics, a relatively long plasma half-life (t1/2), a duration of action allowing once daily administration, and a stable effect independent of interactions with food, antacids and other drugs. Over-the-counter antacids and alginates are widely used, buy may affect absorption of H2 receptor antagonists like cimetidine and ranitidine. Aluminium-containing antacids may, over time, cause toxicity in patients with renal insufficiency. In the treatment of GORD, cisapride presents important advantages over earlier prokinetic compounds, with a longer plasma t1/2, low penetration of the blood-brain barrier and fewer adverse effects. The group of H2 receptor antagonists is still the most frequently use therapy for GORD. Linear pharmacokinetics make dose adjustments easy and safe. In individual patients, suppression of gastric secretion is related to the area under the plasma concentration-time curve (AUC), but there is wide interindividual variation in the effect of the same oral dose. Only with frequent administration and high doses will acid suppression approximate that of proton pump inhibitors. Tolerance, with loss of effect over time, however, is most pronounced in this situation. H2 receptor antagonists seem well suited for on-demand treatment of reflux symptoms, due to the rapid onset of effect and a decrease likelihood of the development of tolerance. Effervescent formulations provide more rapid absorption and almost immediate clinical effect. Cimetidine, however, causes interference with the metabolism of several other drugs in common use. In elderly patients elimination is delayed and in patients with renal insufficiency, dose reductions of all H2 receptor antagonists are recommended. The most effective medical therapy for any severity of GORD, particularly in severe oesophagitis, are the proton pump inhibitors. The substituted benzimidazoles (omeprazole, lansoprazole and pantoprazole), are prodrugs which once trapped and activated in the acid milieu of the gastric glands potently suppress gastric secretion of acid and pepsin. Their long duration of action, more related to the slow turnover of parietal cell H(+)-K+ ATPase molecules, allows once daily administration in most patients. Interindividual variation in bioavailability sometimes calls for higher doses or twice daily administration. Acid suppression is closely related to the AUC. Omeprazole is prone to interaction with the metabolism of other drugs, some of which may e be clinically important. Lansoprazole seems to have an earlier onset of action than omeprazole, ascribed to higher bioavailability during the first days of treatment. Proton pump inhibitors have a slow onset of action, which makes them unsuited for on-demand therapy. Clinical practice in GORD calls for the use of not one but several substances, according to the severity and symptom pattern of the patient. Pharmacokinetic optimisation in the treatment of GORD is a question of selecting the most suitable substances and administration schemes within each group. Cisapride is superior to other prokinetics in terms of longer plasma t1/2 and less toxicity. Amongst H2 receptor antagonists, the more long-acting compounds, ranitidine and famotidine, will improve acidity control througho

Hepatic and cerebrospinal fluid accumulation of aluminium and bismuth in volunteers taking short course anti-ulcer therapy.

To investigate the possible absorption and deposition of bismuth or aluminium from agents used in the treatment of peptic ulcers, we have measured levels of bismuth and aluminium in the liver tissue of 15 patients undergoing elective liver biopsy and in the cerebrospinal fluid (CSF) of 15 patients undergoing elective myelography after administration of standard therapeutic doses of tripotassium dicitrato bismuthate (TBS), sucralfate or aluminium hydroxide for 1 month. Aliquots of liver or CSF were separated and levels of both aluminium and bismuth were assayed in each sample by atomic absorption spectrophotometry. The group who received TBS had significantly higher liver bismuth levels than the other two treatment groups, but there was no significant difference in CSF bismuth levels among the three groups. There was no significant difference in either liver or CSF aluminium levels among the three treatment groups. We conclude that tissue accumulation of bismuth may occur after short-course therapy with colloidal bismuth, although there is no evidence of CNS accumulation of bismuth in the present study.

Selective adherence of a sucralfate-tetracycline complex to gastric ulcers: implications for the treatment of Helicobacter pylori.

The adherence of a sucralfate-tetracycline complex to gastric ulcers and to nearby non-ulcer sites was determined in the rabbit antrum. Persistent gastric ulcers were produced by a previously described method. The presence of the complex was assessed 1 and 4 h after dosing. Drug adherence was determined by quantitation of aluminum in stomach wall biopsies. Significantly more aluminum adhered to ulcer sites than to nearby non-ulcer sites. Adherence of the complex did not significantly decrease from 1 to 4 h. The complexation of tetracycline to sucralfate did not alter the selective adherence of sucralfate to gastric ulcers, providing a mechanism of ulcer site-selective drug delivery in the treatment of Helicobacter pylori gastric ulcer disease.

The treatment of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a common disorder which may result in esophageal ulcers, erosions, strictures and motility disorders if it is not treated promptly. Physician assessment of risk factors and symptoms is essential for accurate diagnosis and determination of appropriate treatment. Mild cases of GERD can be treated with lifestyle modifications and antacid/alginic acid therapy. Moderate and severe GERD can be treated with histamine-2-receptor antagonists (H2RAs) or omeprazole. The H2RAs require split-dosing, at least twice daily, and higher than peptic ulcer disease treatment doses, while omeprazole 20 to 40 mg may be used. Prokinetic agents and sucralfate have been used as adjunctive treatments, however, conflicting data exist about their efficacy. Maintenance therapy is usually required to avoid disease recurrence; either H2RAs or omeprazole may be prescribed.

A single-dose comparison of the bioavailability of aluminium from two formulations of sucralphate in normal volunteers.

The oral bioavailability of aluminium was compared after administration of 1 g sucralphate as either a tablet or a suspension (1 g/5 ml) in a crossover study in 16 healthy volunteers. Aluminium levels were detectable in all subjects pre-dose (21.4 +/- 8.8 micrograms l-1 before tablet; 21.4 +/- 7.4 micrograms l-1 before suspension) and there was a measurable increase in the plasma concentrations of aluminium in all subjects after administration of the suspension, and in 14 of the subjects after administration of the tablet formulation, with Cmax reached within the first 8 h in most subjects. Plasma levels were still elevated 72 h after dosing. The variability in plasma levels of aluminium was significantly higher after administration of the suspension (CV 39-53%) than after administration of the tablet (CV 29-44%), reflecting greater absorption of aluminium from the suspension formulation in three subjects. Similarly, the variance of the Cmax, AUC(0-72 h), and AUC(0-infinity) (for both the raw data and the baseline adjusted data) were all higher for the suspension than for the tablet. A point estimate of the difference of the pharmacokinetic parameters (determined from the median of the arithmetic Walsh averages) indicated little or no difference in Cmax, Tmax, or AUC(0-infinity) in the two formulations. In summary, the performance of the suspension formulation of sucralphate is more variable than the tablet formulation in vivo and some patients may therefore have higher circulating levels of aluminium on therapy with the suspension formulation.