Oral Absorption Test Research Articles

Retrospective analysis of a flucloxacillin oral absorption test in patients requiring flucloxacillin therapy: results and determination of factors associated with adequate absorption

ABSTRACT Objectives Flucloxacillin has the most narrow spectrum to treat staphylococcal infections, but has a large variability in bioavailability which hampers its intravenous (iv) to oral switch. To identify patients with adequate absorption, the use of an oral absorption test (OAT) measuring total plasma concentrations of flucloxacillin before and after an oral dose of 1 gram flucloxacillin, was previously published. The current pilot study aims to evaluate the fraction of patients with adequate absorption using a similar OAT; to assess the therapeutic consequences and to identify potential factors associated with adequate absorption. Methods Demographic data of adult patients treated with iv flucloxacillin and requiring prolonged therapy were collected retrospectively between May 2020 and November 2021 at Ghent University Hospital. A previously published OAT protocol was used, with addition of a protocol for intermittent dosing of iv flucloxacillin. Adequate absorption was defined as an increase in plasma concentration of at least 10 mg/L. Results The flucloxacillin OAT was performed in 99 patients, of which 62% were men, with a median age of 58 years and 95% received intermittent dosing of iv flucloxacillin. Of the 99 patients, 55% had a result indicating an adequate absorption and 49% of all patients were switched to oral flucloxacillin afterwards. Inadequate absorption was found to be associated with higher Body Mass Index and higher flucloxacillin baseline concentration, while co-administration of acetylsalicylic acid was associated with an adequate absorption. Conclusions Based on the OAT, 49% of all patients were switched to oral flucloxacillin instead of broader-spectrum anti-staphylococcal antibiotics. This implicates that an OAT could be a valuable antimicrobial stewardship measure by restricting the use of broad-spectrum antibiotics. For each of the associations found, a hypothesis was formulated about the underlying reason or mechanism; these should be confirmed in future studies with prospective and multicentric design.

The Oral Pheneticillin Absorption Test: An Accurate Method to Identify Patients with Inadequate Oral Pheneticillin Absorption.

Severe streptococcal infections are commonly treated with intravenous followed by oral penicillin (pheneticillin) therapy. However, switching from iv to oral therapy is complicated by the variability in oral pheneticillin absorption. We employed an Oral Absorption Test (OAT) for pheneticillin to identify patients in whom oral pheneticillin absorption is poor. Out of 84 patients 30 patients (36%) were identified as insufficient absorbers. Treatment failure due to pheneticillin malabsorption can be avoided by performing an OAT, and these patients should be treated by another antibiotic, which is known to be absorbed well.

The Clinical Utility of Free Thyroxine in Oral Levothyroxine Absorption Testing

Original absorption studies for levothyroxine (LT4) were validated using total thyroxine (TT4) measurements. Free thyroxine (FT4) has largely supplanted TT4 in clinical practice. The objective of our study was to assess the clinical utility of FT4 in oral LT4 absorption testing. In this retrospective electronic health record analysis, we recorded data of patients who underwent LT4 oral absorption testing between November 2010 and January 2012 because of persistent hypothyroidism despite a greater than anticipated weight-based dose of LT4. Patients included had primary hypothyroidism and an absorption test with assessment of both TT4 and FT4 measured at times 0, 30, 60, 90, 120, 180, 240, 300, and 360 minutes. The test was conducted with 1 mg (five 200-μg tablets) of Synthroid® after an overnight fast by a standard nonisotopic method. A total of 10 patients (3 men/7 women) underwent absorption testing. Prior to testing, the median daily LT4 dose was 250 μg (range, 150 to 350 μg). Three patients were also on liothyronine (10, 20, or 50 μg daily). Based on the calculated amount absorbed, 1 patient demonstrated subnormal absorption, and 9 patients were normal. Median body mass index was 33 kg/m2 (range, 21 to 50 kg/m2). Median calculated absorption was 105% (range, 3.7 to 195.6%). The correlation comparing FT4 and TT4 was 0.88 (95% confidence interval, 0.56 to 0.97; P<.001), a significant correlation. FT4 and TT4 correlated highly, even in patients who were severely hypothyroid; FT4 may be used interchangeably with TT4 as a qualitative assessment of suspected malabsorption using an oral LT4 absorption test.

A Simplified Oral Flucloxacillin Absorption Test for Patients Requiring Long-Term Treatment

Patients with severe methicillin-sensitive Staphylococcus aureus infections are effectively treated with initial continuous intravenous (iv) flucloxacillin followed by oral maintenance therapy. As the absorption of oral flucloxacillin is variable, an oral absorption test (OAT) is used to ensure efficacious therapy. The classical OAT (test A) requires overnight fasting, interruption of iv therapy, and is laborious. We designed a simplified OAT (test B) in which iv therapy is continued and oral dosing is performed after a 1-hour fast. In 43 hospitalized patients on iv flucloxacillin, either test A or test B was performed. In each variant, 1 g of oral flucloxacillin was given, and blood samples were taken before and at 1 and 2 hours after dosing. Flucloxacillin concentration was determined by high-performance liquid chromatography. Adequate absorption was defined as a ≥ 10 mg/L increase in flucloxacillin concentration at 1 or 2 hours after dosing. In a population of 43 patients (18F/25M), test A was done in 19 patients and test B in 24 patients. The groups had similar baseline characteristics such as age, renal function, gender, diagnoses, or comedication. All the patients tolerated the test without problems. The absorption was highly variable between patients. The average (SD; range) maximal increase for test A was 22.3 (11.6; 7-50) mg/L and 26.5 (12.6; 8-53) mg/L for test B. There was no significant difference between the 2 tests (P = 0.23), and 10% of the patients were poor absorbers (increase <10 mg/L). There was no influence of serum creatinine, age, or pretest flucloxacillin concentration. No clinical condition or drug use that may have impaired flucloxacillin absorption could be identified. We designed a simplified OAT that performs well and can be implemented easily. This test may be helpful to rationally and effectively treat patients with severe methicillin-sensitive S. aureus infections with an orally administered small-spectrum antibiotic.

High drug loading self-microemulsifying/micelle formulation: design by high-throughput formulation screening system and in vivo evaluation

Purpose: To design a high drug loading formulation of self-microemulsifying/micelle system.Methods: A poorly-soluble model drug (CH5137291), 8 hydrophilic surfactants (HS), 10 lipophilic surfactants (LS), 5 oils, and PEG400 were used. A high loading formulation was designed by a following stepwise approach using a high-throughput formulation screening (HTFS) system: (1) an oil/solvent was selected by solubility of the drug; (2) a suitable HS for highly loading was selected by the screenings of emulsion/micelle size and phase stability in binary systems (HS, oil/solvent) with increasing loading levels; (3) a LS that formed a broad SMEDDS/micelle area on a phase diagram containing the HS and oil/solvent was selected by the same screenings; (4) an optimized formulation was selected by evaluating the loading capacity of the crystalline drug. Aqueous solubility behavior and oral absorption (Beagle dog) of the optimized formulation were compared with conventional formulations (jet-milled, PEG400).Results: As an optimized formulation, d-α-tocopheryl polyoxyethylene 1000 succinic ester: PEG400 = 8:2 was selected, and achieved the target loading level (200 mg/mL). The formulation formed fine emulsion/micelle (49.1 nm), and generated and maintained a supersaturated state at a higher level compared with the conventional formulations. In the oral absorption test, the area under the plasma concentration-time curve of the optimized formulation was 16.5-fold higher than that of the jet-milled formulation.Conclusions: The high loading formulation designed by the stepwise approach using the HTFS system improved the oral absorption of the poorly-soluble model drug.

Oral absorption tests: absorption site of each substrate.

Three oral absorption tests have been used in patients with short bowel syndrome (SBS) to evaluate the absorption site of each substrate. In this study, three absorption tests were applied: the oral pancreatic function test using N-benzoyl-L-tyrosyl-p-aminobenzoic acid (NBT-PABA), the D-xylose tolerance test, and the oral fat tolerance test. Examinations were performed in eight patients with either a duodenostomy or a jejunostomy located less than 60 cm from the ligament of Treitz, and in a patient with an end ileostomy. Forty-six healthy volunteers participated as controls for the oral fat tolerance test. PABA and D-xylose concentrations were measured in urine. The serum triacylglycerol concentration was determined at 0, 1, 2, and 3 h after ingestion. All eight patients with SBS demonstrated pathologic absorption on each test. We conclude that small bowel integrity is critical for evaluation of the NBT-PABA test. We also determined that the duodenum and proximal jejunum do not play an important role in the absorption of D-xylose and triacylglycerol. We could also evaluate limitations and advantages of the other kinds of oral absorption tests and nutrients through patients with SBS.

Malabsorption of iron in children with iron deficiency

Inability to absorb oral iron is believed to be an extremely rare cause of therapeutic failure in the treatment of iron deficiency anemia. Six patients who had failed to respond to oral iron therapy were studied by a simple oral absorption test and contrasted with 25 patients with untreated iron deficiency anemia and 10 normal subjects. All six of the patients who were therapeutic failures demonstrated impaired iron absorption in the absence of other clinical evidence of gastrointestinal disease. In the 25 newly diagnosed patients with iron deficiency. 24 demonstrated elevated iron absorptions while 10 ironreplete normal subjects had minimal elevations in their serum iron values following the administration of the test dose of 1 mg of elemental iron per kilogram. When the therapeutic failures were treated with parenteral iron, all had a therapeutic response. In addition, after treatment the impaired absorption of iron improved transiently. All children who absorbed iron readily responded to oral iron therapy.

Influence of low dose of steroid therapy on calcium absorption.

ABSTRACT The influence of longterm treatment with 15 mg of prednisolone on calcium absorption was investigated by means of an oral absorption test. Plasma-radioactivity was measured one, two and three hours after the oral dose. Sixteen patients were studied before and while on medication during three weeks, eleven of them being re-investigated after five months of treatment. This dose of steroids produced no effect on calcium absorption; two and three hours after the oral dose the plasma-radioactivity is even higher (P &lt; 0.05) while on prednisolone. In six patients the one hour calcium pool size and turnover rate were also measured after iv 45Ca. The pool size and turnover rate were not changed during the treatment.