s-1743 and posaconazole

s-1743 has been researched along with posaconazole* in 2 studies

Trials

1 trial(s) available for s-1743 and posaconazole

ArticleYear
Effect of pH and comedication on gastrointestinal absorption of posaconazole: monitoring of intraluminal and plasma drug concentrations.
    Clinical pharmacokinetics, 2011, Nov-01, Volume: 50, Issue:11

    Posaconazole (Noxafil®) is an extended-spectrum triazole antifungal agent for prevention and treatment of invasive fungal infections. An inadequate dietary intake and abnormal gastric pH levels are common in critically ill patients receiving antifungal treatment with posaconazole, resulting in unpredictable bioavailability and sub-therapeutic plasma concentrations. This study was carried out to elucidate the impact of pH on posaconazole absorption and to explore the underlying mechanisms of enhanced intestinal absorption when coadministering an acidic carbonated beverage. In contrast to previously published studies, in which only plasma concentrations were determined, we also explored the gastric and intestinal behaviour of posaconazole after a single oral dose.. A crossover study was performed in five healthy subjects. A single dose (10 mL) of posaconazole suspension (40 mg/mL) was administered orally in four different conditions: with 330 mL of water (condition 1); with 330 mL of a cola beverage [Coca-Cola®] (condition 2); with 330 mL of water following intake of the proton pump inhibitor esomeprazole 40 mg once daily for 3 days (condition 3); or with 330 mL of Coca-Cola® following intake of esomeprazole 40 mg once daily for 3 days (condition 4). After administration, gastrointestinal fluid and plasma samples were collected at regular time points, and posaconazole concentrations were determined.. Compared with administration with water, coadministration of Coca-Cola® did not alter the pH of the intraluminal environment but did significantly increase posaconazole gastric concentrations (+102%; p < 0.001) and systemic exposure (+70%; p < 0.05). This enhancement could be attributed to improved posaconazole solubility in Coca-Cola® and prolonged gastric residence. Coadministration of esomeprazole led to an increased gastric pH, which was accompanied by decreased posaconazole absorption; the mean plasma and gastric area under the concentration-time curve (AUC) values decreased by 37% and 84%, respectively. Simultaneous intake of Coca-Cola® could not completely compensate for the increase in pH induced by esomeprazole; compared with the reference condition, the mean plasma and gastric AUC values were still decreased by 19% and 73%, respectively. A good correlation between plasma and gastric posaconazole concentrations was observed (r = 0.8165; p < 0.0001), indicating that dissolution in the stomach dictates absorption of posaconazole.. These results demonstrate that coadministration of Coca-Cola® has a positive effect on posaconazole bioavailability in the fasted state. However, it can only be considered a partially efficient strategy to increase absorption in patients with inadequate food intake who exhibit abnormal gastric pH levels due to coadministration of acid-suppressive agents.

    Topics: Administration, Oral; Adult; Anti-Ulcer Agents; Antifungal Agents; Carbonated Beverages; Cross-Over Studies; Drug Interactions; Esomeprazole; Female; Food-Drug Interactions; Humans; Hydrogen-Ion Concentration; Intestinal Absorption; Male; Triazoles; Young Adult

2011

Other Studies

1 other study(ies) available for s-1743 and posaconazole

ArticleYear
[Prophylaxis use of posaconazole (P) in an hemato-oncology unit: a retrospective study].
    Pathologie-biologie, 2010, Volume: 58, Issue:2

    OBJECTIVE OF THIS STUDY: The mortality level of leucemic patient's fungal infections can reach 70%. Antifungal prophylaxis posaconazole (P) is used during severe and prolonged neutropenia resulting from chemotherapy for acute myelogenous leukemia (AML), myelodysplastic syndrome and after autologous transplant.. We realized a retrospective study in order to assess the efficiency of P. Oral prophylaxy dosage is 200mg every eight hours to beginning before presumed neutropenia. Treatment failure was defined as the occurrence of proven/probable invasive fungal infections (IFI), receipt of any other systemic antifungal agent for suspected IFI or for impossible swallowing and the occurrence of adverse event. The objective is to note down the incidence of proven/probable IFI prevented by P.. We included 22 patients of whom 86% suffered from AML. P was prescribed in IFI prophylaxies during prolonged and severe neutropenia postchemotherapy (72%) or postautologous transplant (28%) and initiated 7 days before neutropenia (50% of cases). The mean treatment period was 18 days. Colonization occurred in one third of patients (43% of Candida albicans). Esomeprazole (E) 40 mg was associated in 64% of cases. P prophylaxis failed in 50% of cases. Proven/probable IFI occurred in one case. Different failure causes were: suspected or possible IFI (n=5) and impossible swallowing (n=5).. P prophylaxis seems to be efficient among these high-risk patients. However, a P tardive initiation, an E association, P administration and resorption difficulties seem to have a importance in successful treatment. It would be interesting to optimize P treatment with plasmatic dosages to ensure efficiency and safety for patients.

    Topics: Adult; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Therapy, Combination; Esomeprazole; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mycoses; Myelodysplastic Syndromes; Neutropenia; Oncology Service, Hospital; Postoperative Complications; Premedication; Retrospective Studies; Transplantation Conditioning; Transplantation, Autologous; Treatment Failure; Triazoles

2010