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).

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).

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.

A common physical basis for the gastric mucosal barrier and the action of sucralfate.

A novel explanation for the action of sucralfate in gastric ulcers has been proposed based on a new theory for gastric mucosal protection derived, in effect, from the very common industrial practice of adsorbing surfactants to surfaces needing protection against acid. Standard physical tests have been employed to show that sucralfate is highly surface-active at both liquid and solid interfaces, with the capability to be adsorbed--but not as active as the indigenous surface-active phospholipid (SAPL). This finding can explain the ability of sucralfate to "bind" to an ulcer site. Unlike SAPL or surfactants in general, adsorbed sucralfate does not render hydrophilic surfaces hydrophobic, suggesting a dual role in substituting for both SAPL and the mucus needed to stabilize it. Electron microscopy, using a novel fixation procedure specifically designed to allow for the known properties of any gastric mucosal barrier, revealed essentially the same oligolamellar lining of SAPL as previously reported in rats. Prolonged (16-day) exposure to sucralfate did not appear to change the situation, whereas there were as many, if not more, lamellar bodies (freshly secreted SAPL) adjacent to the stomach wall. Mucus-free oxyntic ducts showed the same oligolamellar lining as controls. An interesting new finding was the presence of oligolamellar SAPL as the intergranular matrix of gastric mucus--as though preparing to protect the next layer in anticipation of the surface mucin granules being eroded.

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

Short report: plasma aluminium concentration and 24-hour urinary aluminium excretion before, during and after treatment with sucralfate.

Ten dyspeptic patients were treated with 1 g sucralfate q.d.s. for six weeks. The plasma aluminium concentration and 24-h urinary aluminium excretion were measured at 3-weekly intervals before, during and after treatment with sucralfate. Compared with before treatment, there were significant rises in the median plasma aluminium concentration at 3 and 6 weeks during treatment with sucralfate (6 micrograms/L to 13 and 12 micrograms/L). The median 24-h urinary aluminium excretion rose significantly from a pretreatment level of 20 micrograms to 71 and 78 micrograms after 3 and 6 weeks of treatment; the significant increase of urinary aluminium excretion persisted for three weeks after cessation of treatment (52 micrograms/24 hours), but thereafter urinary excretion was not significantly different from pretreatment. The results are consistent with significant absorption and tissue accumulation of aluminium during standard treatment with sucralfate in individuals with normal renal function.

Gastric retention of sucralfate gel and suspension in upper gastrointestinal diseases.

This study was designed to compare by scintigraphy the gastric retention of a new dosage form of sucralfate as gel (Gastrogel) with that of sucralfate suspension in 25 patients with upper gastrointestinal symptoms referred for routine endoscopy. After endoscopy 4 subgroups were defined: macroscopically normal mucosa (n = 7), antral gastritis and/or erosions (n = 6), gastric ulcer (n = 6) and duodenal ulcer (n = 6). Each patient received either sucralfate gel or sucralfate suspension in equivalent doses (5 ml containing 1 g sucralfate). Both formulations were labelled with 111 MBq 99mTc-DTPA before administration. The mean value of t1/2 in the total group was significantly longer when patients were taking sucralfate gel (61.6 min) compared to sucralfate suspension (33.8 min) (P < 0.001). The mean values of t1/2 were significantly longer for sucralfate gel compared to sucralfate suspension also among the subgroups (macroscopically normal P < 0.02, antral gastritis P < 0.05, gastric ulcer P < 0.02 and duodenal ulcer P < 0.05). After 2 and 3 hours, the percentage residual activity in the gastric area was significantly higher following administration of sucralfate gel compared to sucralfate suspension. This study has shown that, compared to sucralfate suspension, sucralfate gel persists longer in the stomach of patients with gastritis and peptic ulcer.

Elevation of serum aluminum in humans on a two-day sucralfate regimen.

Serum aluminum concentrations were determined in ten healthy subjects treated with phenytoin 500 mg and with sucralfate and phenytoin in a crossover fashion. Each subject received four 1,000-mg sucralfate tablets between 8 AM and 10 PM one day before the study, and this was repeated during the study day. A total of eight doses of sucralfate was administered over the two-day period. Serum samples were drawn at 0, 2, 4, 8, 12, 24, 32, and 48 hours after administration. The areas under the serum aluminum concentration-time curves before and after sucralfate (mean +/- SD) were 496.0 +/- 80.9 and 770.9 +/- 146.6 hr-ng/mL, respectively. This increase is statistically significant (P less than .01), indicating that serum aluminum levels are elevated even after two days of treatment with sucralfate. The results from this study are not in agreement with the only other report on this subject.

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.

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.

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.

[Interaction between papaverine hydrochloride and antacids]. / Sorpcja chlorowodorku papaweryny na wybranych lekach przeciwwrzodowych.

The interactions between papaverine hydrochloride and antacids and sucralfate was studied.

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.

[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.

Sucralfate--safety and side effects.

The safety of sucralfate in terms of aluminium absorption, excretion, tissue accumulation, and toxicity is discussed, with special reference to the small amount of aluminium absorbed, its ready excretion by the normal kidney, and the hazard of toxicity in patients with advanced renal failure. The various manifestations of aluminium toxicity are described, and the notion that Alzheimer's disease should be included in this category is refuted. The clinical relevance of possible intraluminal binding and drug-drug interactions in patients receiving sucralfate therapy is also considered. Evidence is presented to show that sucralfate reduces the hyperphosphataemia in chronic uraemia, albeit at the risk of raised blood aluminium levels, but has no measurable effect on normal phosphate levels in patients with good renal function. The bioavailability of phenytoin, fluoroquinolone antibiotics, and H2-receptor blockers may be impaired by concomitant dosing with sucralfate, but normal kinetics are restored by administering the drug 2 h before sucralfate.

Deposition and gastrointestinal transit of conventional sucralfate tablets.

Sucralfate was labelled with 99mTc by the stannous reduction method. Tablets were compressed using 1 g of radioactive sucralfate and suitable additives. On the first test day, five fully informed healthy volunteers were given one radioactive tablet of sucralfate each, following 10 h fasting. On the second test day, the sucralfate tablet was given after a standard meal. The gastrointestinal transit of the 99mTc-labelled sucralfate was evaluated using gamma camera technique. The labelling of sucralfate with 99mTc by the stannous reduction method enables the deposition and the transition of sucralfate in the gastrointestinal tract to be monitored. The tablets disintegrated almost immediately after administration and the released sucralfate distributed homogenously over the entire stomach area, in both fasted and fed subjects. Transit from the stomach into the intestine was noted already 10 min after administration in fasted subjects, whereas the gastric emptying of sucralfate was markedly delayed in fed subjects. To achieve a wider and more homogenous distribution in the GI-tract, sucralfate tablets should be taken before eating.

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.