This study reports a preclinical evaluation of an alginate/chitosan nanoparticle formulation containing NovaBupi®, a racemic bupivacaine (BVC) containing 25% dextrobupivacaine and 75% ...levobupivacaine.
New Zealand White rabbits (n=6) received intraoral or intrathecal injections of BVC 0.5% or BVC 0.5%-loaded alginate-chitosan nanoparticles (BVC
). BVC plasma levels and pharmacokinetic parameters were determined in blood samples of these rabbits. An infraorbital nerve blockade was performed in male Wistar rats (n=7) with the same formulations and the vehicle (NP
). Histological evaluation of local toxicity after 6 hours and 24 hours of the treatments was performed in rats' (n=6) oral tissues.
No statistically significant difference was observed between plasma concentrations and pharmacokinetic parameters (
>0.05) after intraoral injections. However, after intrathecal injection BVC
changed approximately three times the values of volume of distribution and area under the curve (AUC
;
<0.05). The total analgesic effect of BVC after infraorbital nerve blockade was improved by 1.4-fold (
<0.001) with BVC
. BVC and BVC
did not induce significant local inflammatory reaction.
The encapsulation of BVC prolongs the local anesthetic effect after infraorbital nerve blockade and altered the pharmacokinetics after intrathecal injection.
In this study, new drug delivery formulations of tramadol (TR) in thermoreversible gels were studied with regard to the pre-clinical pharmacokinetics (PK) and pharmacodynamics (PD). F2 presented ...significant Pearson correlation between the enhancement of TR / M1 concentrations and miosis (P<0.05). ...the association of PL407 (20%) and PL188 (10%) in...
Summary
Background: Helicobacter pylori treatment failure is a growing problem in daily practice.
Aim: To determine the efficacy of the combination of rabeprazole, levofloxacin and furazolidone as ...a rescue therapy.
Methods: Duodenal ulcer patients previously submitted, without success, to at least two H. pylori treatment regimens were included. Gastroscopy (urease test, histological examination and culture) and 13C‐urea breath test were performed. All patients received a combination of rabeprazole 20 mg, levofloxacin 500 mg and furazolidone 200 mg (two tablets) administered in a single dose in the morning for 10 days. Clinical examination and a new 13C‐urea breath test were performed 90 days after therapy.
Results: Twelve patients (eight females and four males), mean age 43 (30–58) years were included. Two patients failed to complete the treatment because of nausea and vomiting. Ten patients completed the study and took all the medications as advised. Culture was obtained in six patients: 100 and 83% of the samples were sensitive to furazolidone and levofloxacin, respectively. Per‐protocol and intention‐to‐treat eradication rates were 100 and 83% (P = 0.019).
Conclusions: the combination of rabeprazole, levofloxacin and furazolidone in a single daily dose for 10 days constitutes a highly‐effective and low‐cost alternative as a third‐line therapy in patients infected with H. pylori.
We evaluated pharmacokinetics (PK) and pharmacodynamics (PD) induced by new formulations of tramadol (TR) in thermoreversible gels. The poloxamer- (PL-) tramadol systems were prepared by direct ...dispersion of the drug in solutions with PL 407 and PL 188. The evaluated formulations were as follows: F1: TR 2% in aqueous solution and F2: PL 407 (20%) + PL 188 (10%) + TR 2%; F3: PL 407 (25%) + PL 188 (5%) + TR 2%; F4: PL 407 (20%) + TR 2%. New Zealand White rabbits were divided into four groups (n=6) and treated by subcutaneous route with F1, F2, F3, or F4 (10 μg·kg−1). PK evaluation used TR and M1 plasma levels. PD evaluation was performed with the measurement of both pupils’ diameters. F2 showed higher TR plasma concentration after 180 minutes and presented lower M1 concentrations at almost all evaluated periods. Areas under the curve (ASC0–480 and ASC0–∞) and clearance of F2 presented differences compared to F1. F2 presented significant correlation (Pearson correlation) between the enhancement of TR and M1 concentrations and the decrease of pupil size (miosis). Thus, F2 was effective in altering pharmacokinetics and pharmacodynamics effects of TR.
Since patients who regularly take NSAIDS may use sucralfate because of its cytoprotective properties, we examined the influence of this compound on the pharmacokinetics of diclofenac.
Potassium ...diclofenac (105 mg) was administered orally to eighteen healthy male volunteers with or without a 5-day pre-treatment with sucralfate (2000 mg twice daily). Blood samples were collected at intervals post-dose and serum concentrations of diclofenac were determined by reverse-phase h.p.l.c.
Pre-treatment with sucralfate significantly decreased both the AUC(0,8 h) 2265 ng h ml-1 (geometric mean) (range 1815-2827) vs 1821 ng h ml-1 (1295-2562) and the Cmax 1135 ng ml-1 (geometric mean) (range 898-1436) 701 ng ml-1 (501-981) with no significant delay in absorption tmax 1.0 h (median) (range 0.5-2.0) vs 1.0 h (0.5-4.0).
The short-term treatment of healthy male volunteers with sucralfate decreases potassium diclofenac bioavailability. These findings suggest that either an appropriate increase in the diclofenac intake or the use of another gastric mucosa protector must be adopted.
Aims Since patients who regularly take NSAIDS may use sucralfate because of its cytoprotective properties, we examined the influence of this compound on the pharmacokmetics of diclofenac.
Methods ...Potassium diclofenac (105 mg) was administered orally to eighteen healthy male volunteers with or without a 5‐day pre‐treatment with sucralfate (2000 mg twice daily). Blood samples were collected at intervals post‐dose and serum concentrations of diclofenac were determined by reverse‐phase h.p.1.c. Results Pre‐treatment with sucralfate significantly decreased both the AUC(0,8 h) 2265 ng h Ml−1 (geometric mean) (range 1815–2827)vs 1821 ng h ml−’(1295–2562) and the Cmax 1135 ng ml−1 (geometric mean) (range 898–1436) vs 701 ng ml−1 (501–981) with no significant delay in absorption tmax 1.0 h (median) (range 0.5–2.0) vs 1.0 h (0.5‐4.0)l.
Conclusions The short‐tern treatment of healthy male volunteers with sucralfate decreases potassium diclofenac bioavailability. These findings suggest that either an appropriate increase in the diclofenac intake or the use of another gastric mucosa protector must be adopted.
An oral triple therapy using sucralfate instead of a bismuth to eradicate Helicobacter pylori has yielded worse results than those obtained with conventional oral triple therapies. To date, the ...effect of sucralfate on the pharmacokinetics of nitroimidazolic compounds used in triple therapy such as with metronidazole is unknown. The aim of this study was to investigate the effect of a 5-day administration period of sucralfate (2 g b.i.d.) on metronidazole pharmacokinetics.
Fourteen healthy male volunteers were selected. The study had an open randomized 2-period crossover design with a 14-day washout period between the phases. The plasma concentration of metronidazole and its hydroxy-metabolite were measured by reverse-phase HPLC with ultraviolet detection.
No statistically significant difference was observed in any of the pharmacokinetic parameters studied in the absence and presence of sucralfate.
Our results clearly indicate that short-term treatment with sucralfate in healthy volunteers does not alter the extent or the rate of metronidazole absorption, and does not affect metronidazole clearance.
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