Oral Bioavailability and Pharmacokinetics of Trovafloxacin in Patients with AIDS

ABSTRACT Trovafloxacin pharmacokinetics were evaluated in 12 subjects with AIDS. By using a randomized design, single 200-mg doses of oral trovafloxacin and intravenous alatrofloxacin were administered. The mean absolute bioavailability was 91%. The pharmacokinetics of trovafloxacin when administered orally as the active form or intravenously as the prodrug (alatrofloxacin) are not altered in subjects with AIDS compared to those in healthy adults.

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Injectable Dexamethasone Sodium Phosphate Administered Orally? A Pharmacokinetic Analysis of a Common Emergency Department Practice

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-20.2.105 ◽

2015 ◽

Vol 20 (2) ◽

pp. 105-111

Author(s):

Alexander Toledo ◽

Christopher S. Amato ◽

Nigel Clarke ◽

Richard E. Reitz ◽

David Salo

Keyword(s):

Sodium Phosphate ◽

Area Under The Curve ◽

Relative Bioavailability ◽

Healthy Adults ◽

Absolute Bioavailability ◽

Pharmacokinetic Analysis ◽

Pharmacokinetic Data ◽

Open Label ◽

Dexamethasone Sodium Phosphate ◽

The Mean

BACKGROUND: The injectable formulation of dexamethasone has been administered orally, for the treatment of pediatric asthma and croup. The practice is followed in emergency departments around the country, but pharmacokinetic data supporting this practice are lacking. OBJECTIVES: This study evaluated the relative bioavailability and pharmacokinetics of dexamethasone sodium phosphate for injection (DSPI) administered orally compared to dexamethasone oral concentrate (DOC) in healthy adults. METHODS: This was an open label, crossover study of 11 healthy adults 18 to 45 years of age. All subjects received 8 mg of dexamethasone oral concentrate initially. After a 1-week wash-out period, subjects received 8 mg of DSPI administered orally. Dexamethasone levels were measured by liquid chromatography in tandem mass spectrometry. Cmax and area under the curve (AUC (0-t) and AUC (0-∞)) were calculated and compared between groups using the paired t test. RESULTS: The mean ± SD AUC(0-t) for dexamethasone oral concentrate and DSPI were 5497.23 ± 1649 and 4807.82 ± 1971) ng/dL/hr, respectively; 90% confidence interval (CI) was 78.8%–96.9%. The mean ± SD AUC(0-∞) for dexamethasone oral concentrate and DSPI were 6136.43 ± 2577 and 5591.48 ± 3075 ng/dL/hr, respectively; 90% CI was 79.0% –105.2%. Mean Cmax ± SD for DOC and DSPI were 942.94 ± 151 and 790.92 ± 229 ng/dL, respectively; 90% CI 76.8%–91.7%. The relative bioavailability of DSPI administered orally was 87.4% when using AUC(0-t) and 91.1% when using AUC(0-∞). The calculated absolute bioavailability was 75.9%. CONCLUSIONS: DSPI is not bioequivalent to dexamethasone oral concentrate when administered orally. The existing literature supports the efficacy of DSPI despite this. Dosing adjustments may be considered.

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Coadministration of Cyclosporine Strongly Enhances the Oral Bioavailability of Docetaxel

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.4.1160 ◽

2001 ◽

Vol 19 (4) ◽

pp. 1160-1166 ◽

Cited By ~ 146

Author(s):

Mirte M. Malingré ◽

Dick J. Richel ◽

Jos H. Beijnen ◽

Hilde Rosing ◽

Franciska J. Koopman ◽

...

Keyword(s):

Oral Bioavailability ◽

Efflux Pump ◽

Systemic Exposure ◽

Oral Formulation ◽

Absolute Bioavailability ◽

Oral Drug ◽

Time Curve ◽

Glycoprotein P ◽

The Mean ◽

Further Development

PURPOSE: Oral bioavailability of docetaxel is very low, which is, at least in part, due to its affinity for the intestinal drug efflux pump P-glycoprotein (P-gp). In addition, metabolism of docetaxel by cytochrome P450 (CYP) 3A4 in gut and liver may also contribute. The purpose of this study was to enhance the systemic exposure to oral docetaxel on coadministration of cyclosporine (CsA), an efficacious inhibitor of P-gp and substrate for CYP 3A4. PATIENTS AND METHODS: A proof-of-concept study was carried out in 14 patients with solid tumors. Patients received one course of oral docetaxel 75 mg/m2 with or without a single oral dose of CsA 15 mg/kg. CsA preceded oral docetaxel by 30 minutes. During subsequent courses, patients received intravenous (IV) docetaxel 100 mg/m2. RESULTS: The mean (± SD) area under the concentration-time curve (AUC) in patients who received oral docetaxel 75 mg/m2 without CsA was 0.37 ± 0.33 mg·h/L and 2.71 ± 1.81 mg·h/L for the same oral docetaxel dose with CsA. The mean AUC of IV docetaxel 100 mg/m2 was 4.41 ± 2.10 mg·h/L. The absolute bioavailability of oral docetaxel was 8% ± 6% without and 90% ± 44% with CsA. The oral combination of docetaxel and CsA was well tolerated. CONCLUSION: Coadministration of oral CsA strongly enhanced the oral bioavailability of docetaxel. Interpatient variability in the systemic exposure after oral drug administration was of the same order as after IV administration. These data are promising and form the basis for the further development of a clinically useful oral formulation of docetaxel.

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CONCENTRADO PROTEICO OBTIDO DAS FOLHAS DE MANDIOCA (Manihot esculenta Crantz) DE TRÊS VARIEDADES COMERCIAIS.

Revista Acta Ambiental Catarinense ◽

10.24021/raac.v13i1.3296 ◽

2017 ◽

Vol 13 (1) ◽

Author(s):

Izabel Aparecida Soares ◽

Mauro Sérgio Téo ◽

Carlise DEBASTIANI ◽

Suzymeire BARONI ◽

Vanessa Silva RETUCI

Keyword(s):

Manihot Esculenta ◽

Crude Protein ◽

Hydrocyanic Acid ◽

Protein Concentrate ◽

Manihot Esculenta Crantz ◽

White Variety ◽

Mean Values ◽

Randomized Design ◽

Significant Difference ◽

The Mean

O trabalho teve por objetivo verificar diferenças entre rendimento do concentrado proteico e proteína bruta da folha da mandioca (Manihot esculenta Crantz), obtidos a partir de três variedades comerciais: branca, cascuda e vermelha. As manivas foram plantadas seguindo o delineamento experimental inteiramente casualizado com três repetições. Nas comparações entre as variedades, considerou coletas escalonadas pós-plantio, realizadas aos 12, 14 e 16 meses. O concentrado proteico foi obtido a partir da farinha das folhas inteiras e submetido ao método de termo - coagulação ácido e a proteína bruta pelo método padrão AOAC. Os dados foram submetidos a análise de variância e comparados pelo teste de Tukey - 5% de probabilidade. Os resultados não indicaram diferença significativa entre as médias obtidas para rendimento de concentrado proteico. Para a variável porcentagem de proteína bruta a variedade Branca foi a que apresentou maior valor, com média de 46,25%, seguida pela Cascuda e Vermelha, 44,52% e 37,30%, sucessivamente. Conclui-se que outros estudos devem avaliar condições que possam influenciar no teor de proteína foliar, como clima e solo, e, avaliar os níveis de ácido cianídrico de cada variedade, indicando qual das três é a melhor para a extração do concentrado proteico das folhas. Palavras chaves: Manihot esculenta Crantz, variedades comerciais, concentrado proteico, proteína bruta. ABSTRACT: The study aimed to assess the differences between income protein concentrate, crude protein of cassava leaf (Manihot esculenta Crantz), obtained from three commercial varieties: white, red and cascuda. The cuttings were planted following the completely randomized design with three replications. Comparisons between the varieties considered after planting staggered collections, held on 12, 14 and 16 months. The protein concentrate was obtained from flour of whole sheets and subjected to the term method - acid coagulation and crude protein by AOAC standard method. The data were submitted to ANOVA and Tukey test - 5% probability. The results indicated no significant difference between the mean values obtained for protein concentrate income. For the variable percentage of crude protein White variety showed the highest, with an average of 46.25%, followed by cascuda and Red, 44.52% and 37.30%, successively. We conclude that further studies should evaluate conditions that may affect the leaf protein content, such as climate and soil, and evaluate the hydrocyanic acid levels of each variety, indicating which of the three is the best for the extraction of protein concentrate from leaves Key words: Manihot esculenta Crantz, commercial varieties, protein concentrate, crude protein.

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Calibration of Experiments on Perennial Crops using Covariance Analysis: the Case of Coconut

Experimental Agriculture ◽

10.1017/s0014479700014605 ◽

1986 ◽

Vol 22 (4) ◽

pp. 353-361

Author(s):

Tilak Abeysinghe

Keyword(s):

Coefficient Of Variation ◽

Experimental Error ◽

Covariance Analysis ◽

Mean Square ◽

Perennial Crops ◽

Randomized Design ◽

Calibration Experiment ◽

Experimental Yield ◽

The Mean

SUMMARYThe calibrating efficiency of the pre-experimental yield of coconuts was examined using ten years data from a calibration experiment. On the basis of a fully randomized design it was found that the two-year pooled pre-experimental yield on four-tree plots produces consistent calibration and reduces the experimental error mean square by about 73%. This brings down the mean coefficient of variation to 9.7% from its pre-calibration levels of 36 on one-tree plots and 18 on four-tree plots.

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Mouse, rat, and dog bioavailability and mouse oral antidepressant efficacy of (2R,6R)-hydroxynorketamine

Journal of Psychopharmacology ◽

10.1177/0269881118812095 ◽

2018 ◽

Vol 33 (1) ◽

pp. 12-24 ◽

Cited By ~ 10

Author(s):

Jaclyn N Highland ◽

Patrick J Morris ◽

Panos Zanos ◽

Jacqueline Lovett ◽

Soumita Ghosh ◽

...

Keyword(s):

Oral Administration ◽

Learned Helplessness ◽

Oral Bioavailability ◽

Forced Swim Test ◽

Abuse Potential ◽

Absolute Bioavailability ◽

Forced Swim ◽

Antidepressant Effects ◽

Immobility Time ◽

Antidepressant Efficacy

Background: ( R,S)-ketamine has gained attention for its rapid-acting antidepressant actions in patients with treatment-resistant depression. However, widespread use of ketamine is limited by its side effects, abuse potential, and poor oral bioavailability. The ketamine metabolite, ( 2R,6R)-hydroxynorketamine, exerts rapid antidepressant effects, without ketamine’s adverse effects and abuse potential, in rodents. Methods: We evaluated the oral bioavailability of ( 2R,6R)-hydroxynorketamine in three species (mice, rats, and dogs) and also evaluated five candidate prodrug modifications for their capacity to enhance the oral bioavailability of ( 2R,6R)-hydroxynorketamine in mice. Oral administration of ( 2R,6R)-hydroxynorketamine was assessed for adverse behavioral effects and for antidepressant efficacy in the mouse forced-swim and learned helplessness tests. Results: ( 2R,6R)-hydroxynorketamine had absolute bioavailability between 46–52% in mice, 42% in rats, and 58% in dogs. Compared to intraperitoneal injection in mice, the relative oral bioavailability of ( 2R,6R)-hydroxynorketamine was 62%, which was not improved by any of the candidate prodrugs tested. Following oral administration, ( 2R,6R)-hydroxynorketamine readily penetrated the brain, with brain to plasma ratios between 0.67–1.2 in mice and rats. Oral administration of ( 2R,6R)-hydroxynorketamine to mice did not alter locomotor activity or precipitate behaviors associated with discomfort, sickness, or stereotypy up to a dose of 450 mg/kg. Oral ( 2R,6R)-hydroxynorketamine reduced forced-swim test immobility time (15–150 mg/kg) and reversed learned helplessness (50–150 mg/kg) in mice. Conclusions: These results demonstrate that ( 2R,6R)-hydroxynorketamine has favorable oral bioavailability in three species and exhibits antidepressant efficacy following oral administration in mice.

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PERUBAHAN KADAR RAFINOSA, GLUKOSA, MANOSA, ARABINOSA DAN SUKROSA WHEAT POLLARD AKIBAT LAMA STEAM DAN PENAMBAHAN AIR YANG BERBEDA

Jurnal Litbang Provinsi Jawa Tengah ◽

10.36762/litbangjateng.v15i2.412 ◽

2017 ◽

Vol 15 (2) ◽

pp. 161-169

Author(s):

Bambang Sulistiyanto ◽

Sri Kismiati ◽

Cahya Setya Utama

Keyword(s):

Digestive Tract ◽

Starch Content ◽

Short Chain Fatty Acids ◽

Steam Treatment ◽

Sucrose Content ◽

Water Addition ◽

Feed Material ◽

Glucose Levels ◽

Randomized Design ◽

The Mean

Wheat pollard is a waste of the wheat industry and many contain non starch polisacharida (NSP) that interfere with the chicken digestive tract. NSP in wheat pollard can be removed by heating, so it can be used by microbes in the digestive tract of poultry. Utilization of NSP by microbes will result in short chain fatty acids (SCFA), namely acetic acid, propionate and butyrate which have a positive effect on the digestive tract of poultry. The purpose of this study is to examine changes in levels of rafinose, glucose, mannose, arabinose and sucrose in wheat pollard into a source of functional feed for poultry. The benefit of research is to know the technique / manufacture of functional feed material from wheat pollard. The material used in the research is wheat pollard and aquades by using autoclave tool. The design used was a complete randomized design of 2x3 factorial pattern with 3 replications. The first factor is the duration of steam 30 and 60 minutes while the second factor is the addition of water (0, 30 and 60%). The results showed that the addition of water and the duration of different steam strongly influenced (p <0.001) and had interactions on rafinose, mannose, arabinose, sucrose and glucose parameters. The mean of water addition factor increased rafinose level from 1.11+0.03% to 29+0.02% while steam duration decreased raffinose content from 1.99+0.01% to 1.90+0.04%. Glucose levels increased in water addition factor and steam duration from 0.25+0.01% to 1.06+0.12% and 0.54+0.03% to 0.63+0.07%. The mean of water addition factor decreased the mannose level from 0.19+0.01% to 0.06+0.02% and the steam duration increased the manosa level from 0.09+0.01% to 0.15+0.01%. Levels of arabinose increased in water addition factor and steam duration from 0.30+0.03% to 0.98+0.01% and 0.54+0.02% to 0.70+0.04%. The average water addition decreased the sucrose content from 1.80+0.09% to 1.55+0.04% and the steam duration increased the sucrose content from 1.48+0.04% to 1.72+0.03%. The research conclusions that the steam treatment and the addition of water greatly affect the changes of rafinose, glucose, mannose, arabinose and sucrose in wheat pollard and potentially as functional feed. Recommendations that can be given by researchers is the source of feed ingredients that have high starch content should be processed before it is given to poultry so it has a functional value and improve the digestibility of the feed material.

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Differences in Balance Function Between Cancer Survivors and Healthy Subjects: A Pilot Study

Integrative Cancer Therapies ◽

10.1177/1534735418790387 ◽

2018 ◽

Vol 17 (4) ◽

pp. 1144-1149 ◽

Cited By ~ 6

Author(s):

Shinichiro Morishita ◽

Yuta Mitobe ◽

Atsuhiro Tsubaki ◽

Osamu Aoki ◽

Jack B. Fu ◽

...

Keyword(s):

Muscle Strength ◽

Cancer Survivors ◽

Healthy Subjects ◽

Center Of Pressure ◽

Healthy Adults ◽

Body Sway ◽

Balance Function ◽

Adult Cancer Survivors ◽

Eyes Open ◽

The Mean

Older adults who have survived cancer experience significantly more falls compared with healthy adults. Adult cancer survivors may also have a lower balance function than healthy adults. We examined muscle strength and balance function among 19 cancer survivors and 14 healthy subjects. The mean age of the cancer survivors was 51.5 ± 11.2 years; 6 men and 13 women. Cancer diagnoses included breast cancer, retroperitoneal sarcoma, acute leukemia, lung cancer, colorectal cancer, thyroid cancer, Ewing’s sarcoma, and tongue cancer. The mean age of healthy subjects was 47.4 ± 14 years; 3 men, 11 women. Muscle strength was assessed using hand grip and knee extensor strength tests. Balance function was evaluated using the Timed Up and Go (TUG) test, and body sway was tested using a force platform. No significant differences were found with respect to right and left grip strength or right and left knee extension strength between the 2 groups. A significantly higher TUG time was observed in cancer survivors than in healthy subjects ( P < .05). With eyes open, the area of the center of pressure was significantly larger in cancer survivors than in healthy subjects ( P < .05). Similarly, the length per area was significantly lower both with eyes open and closed for cancer survivors than for healthy subjects ( P < .05). TUG was significantly correlated with muscle strength in both groups ( P < .05). However, no body sway parameters were related to muscle strength in either group. Cancer survivors had lower balance function that might not have been related to muscle strength. Cancer survivors should be evaluated for balance function as there is a potential for impairment. The findings of this study will be relevant for planning the prevention of falls for cancer survivors.

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LC478, a Novel Di-Substituted Adamantyl Derivative, Enhances the Oral Bioavailability of Docetaxel in Rats

Pharmaceutics ◽

10.3390/pharmaceutics11030135 ◽

2019 ◽

Vol 11 (3) ◽

pp. 135 ◽

Cited By ~ 1

Author(s):

Seung Han ◽

Qili Lu ◽

Kyeong Lee ◽

Young Choi

Keyword(s):

Oral Bioavailability ◽

Oral Absorption ◽

Ussing Chamber ◽

Absolute Bioavailability ◽

Time Curve ◽

Glycoprotein P ◽

Dose Concentration ◽

Chamber Studies

P-glycoprotein (P-gp)-mediated efflux of docetaxel in the gastrointestinal tract mainly impedes its oral chemotherapy. Recently, LC478, a novel di-substituted adamantyl derivative, was identified as a non-cytotoxic P-gp inhibitor in vitro. Here, we assessed whether LC478 enhances the oral bioavailability of docetaxel in vitro and in vivo. LC478 inhibited P-gp mediated efflux of docetaxel in Caco-2 cells. In addition, 100 mg/kg of LC478 increased intestinal absorption of docetaxel, which led to an increase in area under plasma concentration-time curve (AUC) and absolute bioavailability of docetaxel in rats. According to U.S. FDA criteria (I, an inhibitor concentration in vivo tissue)/(IC50, inhibitory constant in vitro) >10 determines P-gp inhibition between in vitro and in vivo. The values 15.6–20.5, from (LC478 concentration in intestine, 9.37–12.3 μM)/(IC50 of LC478 on P-gp inhibition in Caco-2 cell, 0.601 μM) suggested that 100 mg/kg of LC478 sufficiently inhibited P-gp to enhance oral absorption of docetaxel. Moreover, LC478 inhibited P-gp mediated efflux of docetaxel in the ussing chamber studies using rat small intestines. Our study demonstrated that the feasibility of LC478 as an ideal enhancer of docetaxel bioavailability by P-gp inhibition in dose (concentration)-dependent manners.

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Oral Bioavailability Evaluation of Celastrol-Encapsulated Silk Fibroin Nanoparticles Using an Optimized LC-MS/MS Method

Molecules ◽

10.3390/molecules25153422 ◽

2020 ◽

Vol 25 (15) ◽

pp. 3422

Author(s):

Shuyu Zhan ◽

Amy Paik ◽

Felicia Onyeabor ◽

Baoyue Ding ◽

Sunil Prabhu ◽

...

Keyword(s):

Silk Fibroin ◽

Oral Bioavailability ◽

Rat Plasma ◽

Absolute Bioavailability ◽

Limit Of Quantification ◽

Extraction Solvent ◽

Liquid Liquid Extraction ◽

Silk Fibroin Nanoparticles

Celastrol (CL), a compound isolated from Tripterygium wilfordii, possesses various bioactivities such as antitumor, anti-inflammatory and anti-obesity effects. In previous studies, we developed CL-encapsulated silk fibroin nanoparticles (CL-SFNP) with satisfactory formulation properties and in vitro cancer cytotoxicity effect. For further in vivo oral bioavailability evaluation, in this study, a simple and reliable LC-MS/MS method was optimized and validated to determine CL concentration in rat plasma. The separation of CL was performed on a C18 column (150 by 2 mm, 5 µm) following sample preparation using liquid–liquid extraction with the optimized extraction solvent of tert-butyl methylether. The assay exhibited a good linearity in the concentration range of 0.5–500 ng/mL with the lower limit of quantification (LLOQ) of 0.5 ng/mL. The method was validated to meet the requirements for bioassay with accuracy of 91.1–110.0%, precision (RSD%) less than 9.1%, extraction recovery of 63.5–74.7% and matrix effect of 87.3–101.2%. The developed method was successfully applied to the oral bioavailability evaluation of CL-SFNP. The pharmacokinetic results indicated the AUC0-∞ values of CL were both significantly (p < 0.05) higher than those for pure CL after intravenous (IV) or oral (PO) administration of equivalent CL in rats. The oral absolute bioavailability (F, %) of CL significantly (p < 0.05) increased from 3.14% for pure CL to 7.56% for CL-SFNP after dosage normalization. This study provides valuable information for future CL product development.

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Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial

Nutrients ◽

10.3390/nu11102362 ◽

2019 ◽

Vol 11 (10) ◽

pp. 2362 ◽

Cited By ~ 6

Author(s):

Hidese ◽

Ogawa ◽

Ota ◽

Ishida ◽

Yasukawa ◽

...

Keyword(s):

Cognitive Functions ◽

Verbal Fluency ◽

Controlled Trial ◽

Depression Scale ◽

Healthy Adults ◽

Placebo Administration ◽

Double Blind ◽

Randomized Controlled ◽

Median Split ◽

The Mean

This randomized, placebo-controlled, crossover, and double-blind trial aimed to examine the possible effects of four weeks L-theanine administration on stress-related symptoms and cognitive functions in healthy adults. Participants were 30 individuals (nine men and 21 women; age: 48.3 ± 11.9 years) who had no major psychiatric illness. L-theanine (200 mg/day) or placebo tablets were randomly and blindly assigned for four-week administration. For stress-related symptoms, Self-rating Depression Scale, State-Trait Anxiety Inventory-trait, and Pittsburgh Sleep Quality Index (PSQI) scores decreased after L-theanine administration (p = 0.019, 0.006, and 0.013, respectively). The PSQI subscale scores for sleep latency, sleep disturbance, and use of sleep medication reduced after L-theanine administration, compared to the placebo administration (all p < 0.05). For cognitive functions, verbal fluency and executive function scores improved after L-theanine administration (p = 0.001 and 0.031, respectively). Stratified analyses revealed that scores for verbal fluency (p = 0.002), especially letter fluency (p = 0.002), increased after L-theanine administration, compared to the placebo administration, in individuals who were sub-grouped into the lower half by the median split based on the mean pretreatment scores. Our findings suggest that L-theanine has the potential to promote mental health in the general population with stress-related ailments and cognitive impairments.

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