Reduced Tetracycline Bioavailability Caused by Magnesium Aluminum Silicate in Liquid Formulations of Bismuth Subsalicylate

1997 ◽  
Vol 31 (12) ◽  
pp. 1460-1464 ◽  
Author(s):  
Daniel P Healy ◽  
Richard J Dansereau ◽  
Alisha B Dunn ◽  
Chris E Clendening ◽  
Anthony W Mounts ◽  
...  
Keyword(s):  
Tap Water ◽  
Linear Regression Analysis ◽  
Active Agent ◽  
Tetracycline Hydrochloride ◽  
Aluminum Silicate ◽  
Liquid Formulation ◽  
Maximum Serum ◽  
Bismuth Subsalicylate ◽  
Magnesium Aluminum Silicate

RATIONALE: Bismuth subsalicylate, tetracycline hydrochloride, and metronidazole are widely used in combination for the treatment of Helicobacter pylori infections. As a result, there is renewed interest in the interaction between tetracycline and bismuth subsalicylate. OBJECTIVE: To determine whether the observed decrease in tetracycline bioavailability is due to the active drug bismuth subsalicylate via complexation, or to magnesium aluminum silicate (Veegum), an inactive excipient present only in the liquid formulation of bismuth subsalicylate, which might adsorb the tetracycline, rendering it unavailable for systemic absorption. METHODS: Eleven healthy volunteers participated in a randomized three-period, three-treatment complete crossover study with a 7-day washout interval between treatments. After an overnight fast, subjects received a 500-mg capsule of tetracycline hydrochloride with either tap water, 30 mL of bismuth subsalicylate (525 mg) liquid containing Veegum (Pepto-Bismol), or 30 mL of a specially formulated bismuth subsalicylate (525 mg) liquid without Veegum. Blood was collected for 24 hours after each dose of tetracycline. Serum was assayed for tetracycline concentration by HPLC. In addition, standard in vitro ultraviolet spectrophotometric methods were used to determine the capacity for complexation of bismuth with tetracycline and for adsorption of tetracycline to Veegum. RESULTS: Compared with the reference treatment of tetracycline hydrochloride with water, the liquid formulation of bismuth subsalicylate containing Veegum decreased the maximum serum concentration (Cmax) of tetracycline by 21% and the serum tetracycline AUC by 27% (p < 0.001). The bismuth subsalicylate formulation without Veegum resulted in decreases in Cmax and AUC of 11% and 13%, respectively (p > 0.05 vs. tetracycline hydrochloride with water). Multiple linear regression analysis of the spectral absorbance data demonstrated a calculated recovery of tetracycline of 100.9% and, therefore, a lack of in vitro complexation with bismuth. At pH 1.2, the amount of tetracycline adsorbed to Veegum ranged from 91.5% to 97.2% over the concentration range of 0.25 to 2 mg/mL. At pH 7.0, the values ranged from 82.9% to 83.9% over the concentration range of 0.25 to 1 mg/mL. CONCLUSIONS: In vitro and in vivo data from this study indicate that Veegum, a suspending agent, and not the active agent bismuth subsalicylate, is the primary ingredient in liquid formulations of bismuth subsalicylate responsible for a decrease in tetracycline bioavailability. In addition, the mechanism of interaction is not likely due to complexation between tetracycline and bismuth subsalicylate, as previously postulated, but rather is caused by adsorption of tetracycline to the excipient Veegum, which is present only in the liquid formulation of bismuth subsalicylate. The clinical relevance of this interaction has not been determined.

Dependence of Blood Clot Lysis on the Mode of Transport of Urokinase into the Clot - A Magnetic Resonance Imaging Study in Vitro

1991 ◽  
Vol 65 (05) ◽  
pp. 549-552 ◽  
Author(s):  
A Blinc ◽  
G Planinšič ◽  
D Keber ◽  
O Jarh ◽  
G Lahajnar ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Pressure Difference ◽  
Volume Flow Rate ◽  
Blood Clot ◽  
Linear Regression Analysis ◽  
Imaging Study ◽  
Clot Lysis ◽  
Resonance Imaging

SummaryMagnetic resonance imaging was employed to study the dependence of clot lysing patterns on two different modes of transport of urokinase into whole blood clots. In one group of clots (nonperfused clots, n1 = 10), access of urokinase to the fibrin network was possible by diffusion only, whereas in the other group (perfused clots, n2 = 10) bulk flow of plasma containing urokinase was instituted through occlusive clots by a pressure difference of 3 .7 kPa (37 cm H2O) across 3 cm long clots with a diameter of 4 mm. It was determined separately that this pressure difference resulted in a volume flow rate of 5.05 ± 2.4 × 10−2 ml/min through occlusive clots. Perfused clots diminished in size significantly in comparison to nonperfused ones already after 20 min (p <0.005). Linear regression analysis of two-dimensional clot sizes measured by MRI showed that the rate of lysis was more than 50-times faster in the perfused group in comparison to the nonperfused group. It was concluded that penetration of the thrombolytic agent into clots by perfusion is much more effective than by diffusion. Our results might have some implications for understanding the differences in lysis of arterial and venous thrombi.

Isolation and Identification of a Potent PTP1B Inhibitor, Ursolic Acid, from Carolina Jasmine (Gelsemium sempervirens (L.) J.St.-Hil.)

2020 ◽  
Vol 17 (12) ◽  
pp. 939-943
Author(s):  
Toshiro Noshita ◽  
Yusuke Kakizoe ◽  
Satoshi Tanabe ◽  
Hidekazu Ouchi ◽  
Akihiro Tai
Keyword(s):  
Ursolic Acid ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Active Agent ◽  
Protein Tyrosine Phosphatase 1B ◽  
Inhibiting Activity ◽  
Inhibition Activity ◽  
Isolation And Identification ◽  
Gelsemium Sempervirens

Extracts of Carolina jasmine (Gelsemium sempervirens (L.) J.St.-Hil.) petals were evaluated in vitro for inhibition activity against protein tyrosine phosphatase 1B (PTP1B). The principle active agent was also isolated from the extract and identified as ursolic acid (1). This is the first report of ursolic acid from G. sempervirens and of PTP1B-inhibiting activity in the genus Gelsemium.

scholarly journals 1592. Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales and Pseudomonas aeruginosa With Overexpression of AmpC β-Lactamase From Phase 3 Clinical Trials

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S792-S793
Author(s):  
Lynn-Yao Lin ◽  
Dmitri Debabov ◽  
William Chang ◽  
Urania Rappo
Keyword(s):  
Clinical Trials ◽  
Active Agent ◽  
Complicated Urinary Tract Infection ◽  
Carbapenem Resistance ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Control Groups ◽  
In Vitro Susceptibility ◽  
Intra Abdominal Infection

Abstract Background AmpC overproduction is a main mechanism of carbapenem resistance, in the absence of acquired carbapenemases. Ceftazidime-avibactam (CAZ-AVI) has potent in vitro activity against AmpC-producing P. aeruginosa and Enterobacterales that are resistant to carbapenems and other β-lactams. Methods Activity of CAZ-AVI and comparators was evaluated against AmpC-overproducing Enterobacterales (n=77) and P. aeruginosa (n=53) collected from 4 CAZ-AVI clinical trials: RECLAIM (complicated intra-abdominal infection [cIAI]), REPRISE (cIAI/complicated urinary tract infection [cUTI]), RECAPTURE (cUTI) and REPROVE (hospital-acquired pneumonia/ventilator associated pneumonia). In vitro susceptibility of CAZ-AVI and comparators was performed by broth microdilution using ThermoFisher custom panels. CLSI breakpoints were used to determine susceptibility. Quantitative PCR and microarray data were used to characterize presence and expression of AmpC. Clinical response at test of cure was assessed. Results Against 77 AmpC-overproducing Enterobacterales isolates, meropenem-vaborbactam (MVB) (98.7% susceptible [S]), CAZ-AVI (96.1% S), and meropenem (MEM) (96.1% S) had similar in vitro activity (Table), with greater in vitro activity than amikacin (AMK) (84.4% S), gentamicin (61.0% S), and ceftolozane-tazobactam (TZC) (35.1% S). Clinical cures in patients with baseline AmpC-overproducing Enterobacterales were 21/26 (81%) in CAZ-AVI group vs 17/20 (85%) in control groups. Against 53 AmpC-overproducing P. aeruginosa isolates, CAZ-AVI (73.6% S) showed greater in vitro activity than AMK (69.8% S), TZC (58.5% S), and MEM (37.7% S). Clinical cures in patients with baseline AmpC-overproducing P. aeruginosa were 12/14 (86%) in CAZ-AVI group vs 9/12 (75%) in control groups. MIC distributions against the same P aeruginosa isolates were CAZ-AVI (MIC50/90, 4/ &gt;64 µg/mL), MVB (MIC50/90, 8/32 µg/mL), and MEM (MIC50/90, 8/32 µg/mL). Table Conclusion CAZ-AVI was the most active agent against AmpC-overproducing P. aeruginosa with higher proportion of clinical cure than controls. CAZ-AVI was also among the most active agents against AmpC-overproducing Enterobacterales, with &gt;96% isolates susceptible. Disclosures Lynn-Yao Lin, MS, AbbVie (Employee) Dmitri Debabov, PhD, AbbVie (Employee) William Chang, BS, AbbVie (Employee) Urania Rappo, MD, MS, PharmD, Allergan (before its acquisition by AbbVie) (Employee)

scholarly journals Effects of bismuth subsalicylate and calcium-ammonium nitrate on ruminal in vitro fermentation of bahiagrass hay with supplemental molasses

animal ◽  
2021 ◽  
Vol 15 (5) ◽  
pp. 100195
Author(s):  
D.D. Henry ◽  
F.M. Ciriaco ◽  
R.C. Araujo ◽  
M.E. Garcia-Ascolani ◽  
P.L.P. Fontes ◽  
...  
Keyword(s):  
Ammonium Nitrate ◽  
In Vitro Fermentation ◽  
Calcium Ammonium Nitrate ◽  
Bismuth Subsalicylate

scholarly journals 1463. Activity of Delafloxacin against Multi-Drug-Resistant Fastidious Respiratory Pathogens from European Medical Centers (2014-2019)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S733-S733
Author(s):  
Dee Shorttidge ◽  
Jennifer M Streit ◽  
Michael D Huband ◽  
Robert K Flamm
Keyword(s):  
Active Agent ◽  
The United States ◽  
Multidrug Resistant ◽  
Respiratory Pathogens ◽  
Services Research ◽  
In Vitro Susceptibility ◽  
Amoxicillin Clavulanate ◽  
Tract Infections ◽  
Research Grant

Abstract Background Delafloxacin (DLX) is an anionic fluoroquinolone (FQ) that has been approved in the United States and in Europe for the treatment of acute bacterial skin and skin structure infections and was recently approved in the US for treatment of community-acquired bacterial pneumonia (CABP). In the present study, in vitro susceptibility (S) results for DLX and comparator agents were determined for CABP pathogens including Streptococcus pneumoniae (SPN), Haemophilus influenzae (HI), H. parainfluenzae (HP) and Moraxella catarrhalis (MC) clinical isolates from European hospitals participating in the SENTRY Program during 2014-2019. Methods A total of 2,835 SPN, 1,484 HI, 959 MC, and 20 HP isolates were collected from community-acquired respiratory tract infections (CARTI) during 2014-2019 from European hospitals. Sites included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology, and EUCAST (2020) breakpoints were applied where applicable. Other antimicrobials tested included levofloxacin (LEV) and moxifloxacin (MOX; not tested in 2015). Multidrug-resistant (MDR) SPN isolates were categorized as being nonsusceptible (NS) to amoxicillin-clavulanate, erythromycin (ERY), and tetracycline; other SPN phenotypes were ERY-NS, or penicillin (PEN)-NS. β-lactamase (BL) presence was determined for HI, HP, and MC. Results The activities of the 3 FQs are shown in the table. The most active agent against SPN was DLX, with the lowest MIC50/90 values of 0.015/0.03 mg/L. DLX activities were the same when tested against the MDR or PEN-NS for SPN phenotypes. ERY-NS isolates had DLX MIC50/90 results of 0.015/0.03 mg/L. DLX was the most active FQ against HI, HP, and MC. BL presence did not affect FQ MIC values for HI or MC; only 1 HP isolate was BL-positive. Conclusion DLX demonstrated potent in vitro antibacterial activity against SPN, HI, HP, and MC. DLX was active against MDR SPN that were NS to the agents commonly used as treatments for CABP. These data support the utility of DLX in CABP including when caused by antibiotic resistant strains. Table 1 Disclosures Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Robert K. Flamm, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)

scholarly journals 1375. In vitro Activity of Cefiderocol and Comparator Agents against Gram-Negative Isolates from Cancer Patients

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S421-S422 ◽  
Author(s):  
Kenneth V I Rolston ◽  
Bahgat Gerges ◽  
Issam Raad ◽  
Samuel L Aitken ◽  
Ruth Reitzel ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Active Agent ◽  
Vitro Activity ◽  
Significant Activity ◽  
In Vitro Activity ◽  
Research Support ◽  
Gram Negative ◽  
E Coli ◽  
Research Grant

Abstract Background Gram-negative bacilli (GNB) are now the predominant cause of bacterial infection in cancer patients (CP). Many GNB are problematic because they have become resistant to commonly used antibiotics. Cefiderocol (CFDC), a novel siderophore cephalosporin, is active against a wide spectrum of GNB. We evaluated its in vitro activity and that of eleven comparator agents against GNB isolated from CP. Methods A total of 341 recent GNB blood isolates from CP were tested using CLSI approved methods for MIC determination by broth microdilution. Comparator agents were amikacin (A), aztreonam (AZ), ceftazidime (CZ), ceftazidime/avibactam (CAV), cefepime (CEF), ciprofloxacin (CIP), colistin (CL), meropenem (MR), ceftolozane/tazobactam (C/T), tigecycline (TG), and trimethoprim/sulfamethoxazole (T/S). Results CFDC MIC90s as mg/L were: S. maltophilia [50 isolates] 0.25, E. coli (ESBL−) [50 isolates] 0.5, E. coli (ESBL+) [51 isolates] 2.0, K. pneumoniae (ESBL− and +) [60 isolates] 0.5; K. pneumoniae (CRE) [22 isolates] 2.0; P. aeruginosa (MDR) [32 isolates] 1.0; E. cloacae [27 isolates] 4.0; Achromobacter spp. [15 isolates] 0.12. CFDC inhibited P. agglomerans, Burkholderia spp., Sphingomonas spp., Ochrobactrum spp. at ≤1 mg/L [23 total isolates] and Elizabethkingia spp. and R. radiobacter at ≤8 mg/L [11 total isolates]. Among comparator agents, only T/S had consistent activity against S. maltophilia. For E. coli (ESBL− and +) MR, TG, CAV, CL were most active. For K. pneumoniae (ESBL–and +) MR, CAV were most active. For K. pneumoniae (CRE) and P. aeruginosa (MDR), none of the comparators had significant activity. For E. cloacae, MR, A, CAV, TG were most active. Among the uncommon organisms, MR and TG had the greatest activity. Conclusion Although susceptibility breakpoints have yet to be determined, CFDC has significant activity (≤4 mg/L) against most problematic Gram-negative organisms causing infections in CP based on available pharmacokinetic/pharmacodynamic data. In particular, its activity against S. maltophilia was superior to the comparators. Also, it was the most active agent against P. aeruginosa (MDR) and K. pneumoniae (CRE). Based on our results, CFDC warrants clinical evaluation for the treatment of blood stream infections caused by GNB in CP. Disclosures K. V. I. Rolston, Merck: Investigator, Research grant; JMI Laboratories: Investigator, Research grant; Shionogi (Japan): Investigator, Research grant. B. Gerges, Shionogi: Collaborator, Research support. S. L. Aitken, Shionogi: Scientific Advisor, Consulting fee; Merck: Scientific Advisor, Consulting fee; Medicines Co: Scientific Advisor, Consulting fee; Achaogen: Scientific Advisor, Consulting fee; Zavante: Scientific Advisor, Consulting fee; R. Prince, Shionogi: Investigator, Research support. Merck: Investigator, Research support.

In Vivo Testing of Sericin-Polyurethane Nanofiber Mats for Wound Healing in Rats

2017 ◽  
Vol 751 ◽  
pp. 581-585 ◽  
Author(s):  
Piyaporn Kampeerapappun ◽  
Pornpen Siridamrong
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Active Agent ◽  
L929 Cell ◽  
Wound Healing Process ◽  
Original Size ◽  
Nanofiber Mats ◽  
Dressing Materials

The objective of this study was to investigate sericin-polyurethane nanofiber cover (SUC) for wound dressing materials in a rat skin. Sericin-polyurethane blended nanofibers were fabricated by using electrospinning. The composition of 3%w/v polyurethane in ethanol and 19% w/v sericin were blended and electrospun at 15 kV, 20 cm from tip to collector with a feed rate of 6.2 ml/hr. The mats, approximately 1.5 mm thick, were sterile by gamma irradiation with a radiation dose of 15 kGy. The samples of in vitro and in vivo testing were separated into three groups; gauze, polyurethane nanofiber cover (UC), and SUC. In vitro cultured L929 cell lines were investigated with inverted microscope. It was found that cells migrated to SCU. For in vivo tests, the remaining wound in rats was measured on day 2-14 after excision. Compared to original size of wound samples, the size of the wound remained 24% for SUC, 33% for gauze, and 34% for UC at day 8. The sericin, an active agent, contained in SUC mats was about 5 µl at 1.5 ×1.5 cm. It can be concluded that sericin is non-toxic to cells and can promote wound healing process in rats.

Novel chitosan−magnesium aluminum silicate nanocomposite film coatings for modified-release tablets

2011 ◽  
Vol 407 (1-2) ◽  
pp. 132-141 ◽  
Author(s):  
Wanwisa Khunawattanakul ◽  
Satit Puttipipatkhachorn ◽  
Thomas Rades ◽  
Thaned Pongjanyakul
Keyword(s):  
Nanocomposite Film ◽  
Aluminum Silicate ◽  
Modified Release ◽  
Film Coatings ◽  
Magnesium Aluminum Silicate
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