ABSTRACT
The Pistia stratiotes L. was tested for phytoremediation potential of the compound clomazone in water. Clomazone is a post-emergent herbicide marketed as Gamit®. Five groups with four samples each were evaluated, a low concentration control (LCC: 37.86â¯mgâ¯L-1), low concentration treatment (LCT: 38.16â¯mgâ¯L-1), high concentration control (HCC: 54.71â¯mgâ¯L-1), high concentration treatment (HCT: 54.33â¯mgâ¯L-1), and a plant control group (PCG). Plant resistance to clomazone at determined concentrations and their ability to remove the herbicide from water by HPLC over 24 days were evaluated. The results demonstrate that P. stratiotes has high resistance to clomazone exposure and was able to eliminate up to 90% of the herbicide residues during the experimental period. Under dissipation by P. stratiotes in water, clomazone had a halflife of 19.6 days for in the control treatments, LCC and HCC, and 8.0 days in the treatment groups, LCT and HCT. This study indicates that Pistia stratiotes is an effective phytoremediation agent for the herbicide clomazone in water.
Subject(s)
Araceae/drug effects , Biodegradation, Environmental , Isoxazoles/adverse effects , Oxazolidinones/adverse effects , Water Resources , Araceae/physiology , Drug Tolerance , Herbicides/adverse effects , Isoxazoles/pharmacokinetics , Oxazolidinones/pharmacokinetics , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/isolation & purificationABSTRACT
BACKGROUND: Risperidone (RSP) is a benzisoxazole antipsychotic agent used to treat schizophrenia and other psychiatric illnesses in adults and children (including those with autism). After oral administration, RSP is completely absorbed from the gastrointestinal tract and undergoes hydroxylation to yield 9-hydroxyrisperidone (9-OH-RSP), an active metabolite that has a pharmacologic profile and potency similar to RSP. OBJECTIVES: The aims of this study were to compare the relative bioavailability of a pharmaceutical-equivalent (test) formulation with a reference formulation of oral RSP 2 mg, both available commercially on the Brazilian pharmaceutical market, and to generate data regarding the oral bioavailability of the tested drug in healthy Brazilian volunteers. METHODS: This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Brazilian volunteers from August to December 2008. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa, with a 30-day washout period between doses. Study drugs were administered after a 12-hour overnight fast. For pharmacokinetic analysis, blood samples were drawn at 0 (baseline), 0.25, 0.5, 1, 1.5, 3, 5, 8, 12, 24, 48, 72, 96, and 120 hours after administration. Plasma concentrations of RSP and 9-OH-RSP were determined using LC-MS/MS. The test and reference formulations were to be considered bioequivalent if the 90% CIs for the geometric mean test/reference ratios were within a predetermined range of 80% to 125%, in accordance with the policies of the Brazilian Sanitary Surveillance Agency and the US Food and Drug Administration. Tolerability was determined using clinical assessments, monitoring of vital signs, analysis of laboratory test results, and subject interviews regarding adverse events. RESULTS: A total of 22 subjects were enrolled (11 men, 11 women; mean [SD] age, 32 [12] years [range, 1858 years]; weight, 70.4 [11.9] kg [range, 50-103 kg]; height, 1.67 [0.08] m [range, 1.56-1.80 m]; and body mass index, 25 [4] kg/m(2) [range, 18-29 kg/m(2)]). For RSP, mean (SD) C(max) values were 12.6 (2.7) and 16.0 (2.3) ng/mL for the test and reference formulations, respectively. For 9-OH-RSP, mean Cmax values were 17.8 (1.3) and 21.0 (1.7) ng/mL for the test and reference formulations. The 90% CIs for the mean test/ reference ratios for RSP C(max), AUC(0-120), and AUC(0-∞) were 74% to 82%, 75% to 85%, and 76% to 85%, respectively, and 83% to 87%, 75% to 79%, and 75% to 78% for 9-OH-RSP. The related adverse events (headache, low back pain, drowsiness, standing hypotension, local postvenipuncture ecchymoses, insomnia, nausea, and vomiting) were transient and mild. CONCLUSIONS: This single-dose study found that the test and reference formulations of oral RSP 2 mg did not meet the Brazilian and US regulatory criteria for bioequivalence in these fasting, healthy volunteers. The study formulations appeared to be well tolerated.
Subject(s)
Antipsychotic Agents/pharmacokinetics , Isoxazoles/pharmacokinetics , Pyrimidines/pharmacokinetics , Risperidone/pharmacokinetics , Administration, Oral , Adult , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effects , Area Under Curve , Biological Availability , Brazil , Chromatography, Liquid , Cross-Over Studies , Female , Humans , Isoxazoles/blood , Male , Middle Aged , Paliperidone Palmitate , Pyrimidines/blood , Risperidone/administration & dosage , Risperidone/adverse effects , Tandem Mass Spectrometry , Therapeutic EquivalencyABSTRACT
Toxic epidermal necrolysis is a potentially fatal disease due to allergic reactions to drugs. We report on a 58 years old female, that presented Raynaud sphenomenon during 20 years. During the last year, she developed polyarthritis of hands, shoulders, knees and ankles. Rheumatoid factor (RF), antinuclear antibodies (ANA) and U_ ribonucleoprotein (U1 RNP) were present, and Mixed connective tissue disease was suspected. Because of a poor response to methotrexate the patient received leflunomide. Two weeks later, she began with fever, pruritus and generalized edema. Within days this affected her neck, thorax, eyes and oral mucous. She had bullaes and areas of epidermic detachment. A toxic epidermal necrolysis was diagnosed and treated with IV immunoglobulins. The lesions disappeared successfully. In addition to the dermatological problem, the patient later presented ocular complications that required the transplant of both corneal, with the sub-sequent loss of one of her eyes.
Subject(s)
Humans , Female , Middle Aged , Isoxazoles/toxicity , Stevens-Johnson Syndrome , Antidotes , Antirheumatic Agents/toxicity , Anaphylaxis/chemically induced , Immunoglobulins, Intravenous/therapeutic use , Isoxazoles/adverse effects , Isoxazoles/pharmacokinetics , Isoxazoles/therapeutic use , Stevens-Johnson SyndromeABSTRACT
The degradation kinetics of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone 4-imine (1) in a 25% solution of ethyl alcohol in water has been studied. The rate constants were observed to follow pseudo-first-order kinetics in all cases. The pH-rate profile indicated a negligible decomposition at pH values higher than its pKa2 value [5.4 +/- 0.14 (*n = 6)]. Un-ionized 1 was subject to specific acid catalysis. The ionic strength did not affect the stability of the drug. These data can be used to develop a stable oral liquid dosage form of the drug.