scholarly journals Effects of Transcutol P and Precirol ATO-5 on Percutaneous Absorption of Flutamide from Emulgels

2021 ◽  
Author(s):  
Parandis Khalilollah ◽  
Javad Shokri ◽  
Seyedehzahra Ahmadi ◽  
Farnaz Monajjemzadeh
Keyword(s):  
Percutaneous Absorption ◽  
High Performance ◽  
Area Under The Curve ◽  
Diffusion Cell ◽  
Rat Skin ◽  
Androgenic Alopecia ◽  
Absorption Enhancers ◽  
Franz Diffusion Cell ◽  
Drug Concentrations ◽  
Male Pattern

Background: Flutamide is a non-steroidal anti-androgenic agent which is not only used in treating prostate cancer but also can be effective in some disorders such as androgenic alopecia and male pattern baldness. Several serious side effects for systemic administration of flutamide can be overcome by emulgel dosage form. Absorption enhancers can promote permeation of flutamide through skin. Percutaneous absorption of Flutamide emulgels with different concentrations of Transcutol P and Precirol ATO5 was studied. Methods: Various emulgel formulations using different concentration of Transcutol P and Precirol ATO5 with 0.5 to 5 % w/w were prepared. Percutaneous absorption was tested with standard Franz Diffusion Cell equipment using full thickness rat skin. Drug concentrations in the samples were analyzed by High-Performance Liquid Chromatography (HPLC) equipped with UV-Vis detector at 305 nm. Results: The percutaneous absorption of flutamide emulgels formulated with enhancers was higher than control formulations. Enhancement ratio increased from 1.218 to 3.670 and 1.346 to3.900 for Precirol ATO5 and Transcutol P, respectively. Area under the Curve (AUC) increased by increase the enhancers’ concentration and a significant upsurge was seen in the concentration 1% for both enhancers. Conclusion: The flutamide emulgel containing 1% Transcutol P showed more appropriate percutaneous absorption through the skin compared to others.

Mitomycin C pharmacokinetics in patients with recurrent or metastatic colorectal carcinoma

1987 ◽  
Vol 65 (3) ◽  
pp. 407-411 ◽  
Author(s):  
Charles Erlichman ◽  
A. Michael Rauth ◽  
Rena Battistella ◽  
Sheldon Fine
Keyword(s):  
Colorectal Carcinoma ◽  
Mitomycin C ◽  
High Performance ◽  
Single Agent ◽  
Area Under The Curve ◽  
Metastatic Colorectal Carcinoma ◽  
Active Metabolites ◽  
Small Component ◽  
Drug Concentrations ◽  
Hplc Technique

The pharmacokinetics of mitomycin C as a single agent have been determined in 25 treatment courses given to 18 patients with recurrent or metastatic colorectal carcinoma using a high performance liquid chromatography (HPLC) assay to analyze plasma and urine samples. The plasma pharmacokinetics conformed to a two-compartment linear model in 21 of 25 courses monitored with a mean t½λ1 of 9.8 ± 1.2 (SEM) min and mean t½λz of 64.1 ± 8.9 (SEM) min. The large variation observed in t½λz was not related to dose or treatment, but an interaction of these two factors approached significance (p = 0.057). Renal excretion in the 12 courses in which it was determined averaged only 2.3% of the total administered dose during the first 4 h monitored and no mitomycin C metabolites were detected in plasma or urine by the HPLC technique used. The most common toxicity, thrombocytopenia, did not correlate with t½λz or the area under the curve. This may be due to (i) a failure to monitor active metabolites of mitomycin C; (ii) other factors besides plasma drug concentrations that mediate toxicity towards marrow elements; or (iii) the small number of courses associated with thrombocytopenia (<100 000/mm3). Our study indicates that (i) an interaction of drug dose and treatment course may be associated with increasing t½λz; (ii) the renal clearance contributes a small component of mitomycin C elimination; (iii) metabolites of mitomycin C cannot be detected by the present HPLC technique; and (iv) routine monitoring of mitomycin C using present methods cannot be recommended for clinical use to predict toxicity.

Validation of an In vitro-in vivo Assay System for Evaluation of Transdermal Delivery of Caffeine

2019 ◽  
Vol 9 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Fanni Farner ◽  
Luca Bors ◽  
Ágnes Bajza ◽  
Gellért Karvaly ◽  
István Antal ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Assay System ◽  
Diffusion Cell ◽  
Rat Skin ◽  
Topical Formulation ◽  
Franz Diffusion Cell ◽  
Topical Drugs ◽  
In Vivo Assay

Introduction: Degree of skin penetration of topical drugs and cosmetics is a crucial point concerning their effects and tolerability. For testing drug delivery across the dermal barrier different in vitro and in vivo assays have been developed. Caffeine has been shown to have beneficial effects against skin aging, sunburn and hair-loss, and it is protective against melanoma and non-melanoma type skin cancers. Aim of our study was to set up an assay system to evaluate caffeine penetration from topical formulation into the skin. </P><P> Methods: Franz diffusion cells consisting of either a filter paper or an artificial membrane or rat skin were used as in vitro/ex vivo test systems and transdermal microdialysis in anaesthetized rats was performed as an in vivo assay. </P><P> Results: Results indicate that Franz diffusion cell studies provide a good approximation of the release of caffeine from the formulation but are not able to differentiate between 2% and 4% cream concentrations. The maximum concentrations (Cmax) in case of the 2% cream formulation were 708.3 (2.7 μm pore), 78.7 (0.8 &#181;m pore), 45.3 (0.45 &#181;m pore) and 44.9 (rat skin) &#181;g/7.5 mL, respectively. The in vivo microdialysis experiments were in accordance with the in vitro and ex vivo results and gave more information on the dynamics and follicular and transcellular phases of drug penetration through the layers of the skin. </P><P> Discussion and Conclusion: Taken together, Franz diffusion cell and transdermal microdialysis are a good combination to evaluate caffeine release and penetration into the skin from the formulations tested. This system might also be used for rapid testing of other hydrophilic topical drugs and has a benefit in the prediction for human skin absorption and tolerability studies, in an early phase of drug development.

scholarly journals PENETRATION TEST OF CAFFEINE IN ETHOSOME AND DESMOSOME GEL USING AN IN VITRO METHOD

2017 ◽  
Vol 9 ◽  
pp. 120
Author(s):  
Iskandarsyah Iskandarsyah ◽  
Alvina Wijaya Puteri ◽  
Ernysagita Ernysagita
Keyword(s):  
Dimethyl Sulfoxide ◽  
Percutaneous Absorption ◽  
Lipid Vesicles ◽  
Penetration Enhancer ◽  
Diffusion Cell ◽  
Penetration Test ◽  
In Vitro Method ◽  
Franz Diffusion Cell

Objectives: Caffeine has many functions including its use in the field of cosmetics. Nonetheless, the percutaneous absorption of caffeine is very low(9%), and the penetration of a substance such as caffeine in the skin is not desirable. Ethosomes and desmosomes are lipid vesicles created by themodification of liposomes containing phospholipids and ethanol or dimethyl sulfoxide (DMSO) as the penetration enhancer. The purpose of this studywas to compare the effectiveness of ethosomes and desmosomes as vesicles in increasing the penetration of caffeine.Methods: Ethosomes and desmosomes were prepared using phosphatidylcholine, ethanol/DMSO, and caffeine. Phosphatidylcholine was used in theform of phospholipon 90 g that was obtained from soybeans. Observations were done including the characteristic of ethosomes and desmosomes,organoleptic observation, homogeneity observation, and in vitro penetration test using Franz diffusion cell method.Results: The cumulative penetration of caffeine ethosome gel is 3316.46±218.51 μg/cm2, with flux 249.45±30.06 μg·cm−2·hr−1, and 62.35±4.52%. Thecumulative penetration of the desmosome gel is 2954.95±222.87 μg/cm2 with flux 381.68±34.91 μg·cm−2·hr−1 and 53.4±3.65%.Conclusions: It can be concluded that ethosome is more effective than desmosome in increasing the penetration of caffeine.

Influence of novel percutaneous absorption enhancers, cyclohexanone and piperidone derivatives, on histopathology of rat skin

1991 ◽  
Vol 68 (1-3) ◽  
pp. 239-253 ◽  
Author(s):  
Quan Danyi ◽  
Takayama Kozo ◽  
Mitsuzono Toji ◽  
Isowa Koichi ◽  
Nagai Tsuneji
Keyword(s):  
Percutaneous Absorption ◽  
Rat Skin ◽  
Absorption Enhancers

scholarly journals Efavirenz Pharmacokinetics in Cerebrospinal Fluid and Plasma over a 24-Hour Dosing Interval

2012 ◽  
Vol 56 (9) ◽  
pp. 4583-4585 ◽  
Author(s):  
Aylin Yilmaz ◽  
Victoria Watson ◽  
Laura Dickinson ◽  
David Back
Keyword(s):  
Cerebrospinal Fluid ◽  
High Performance ◽  
Area Under The Curve ◽  
Dosing Interval ◽  
Lumbar Drain ◽  
Chromatography Tandem Mass Spectrometry ◽  
Drug Concentrations ◽  
Liquid Chromatography Tandem Mass ◽  
Median Plasma ◽  
Csf Concentration

ABSTRACTWe determined the pharmacokinetics of efavirenz in plasma and cerebrospinal fluid (CSF) over a 24-h dosing interval in a patient who had undergone a lumbar drain because of cryptococcal meningitis. Drug concentrations were determined by high-performance liquid chromatography-tandem mass spectrometry in paired CSF (n= 24) and plasma (n= 25) samples. The median plasma efavirenz concentration was 3,718 ng/ml (range, 2,439 to 4,952), and the median CSF concentration was 16.3 ng/ml (range, 7.3 to 22.3). The CSF/plasma area-under-the-curve ratio was 0.0044 corresponding to a CSF penetration of 0.44% of plasma.

scholarly journals Sphingolipid Analysis Indicate Lactosylceramide as a Potential Biomarker of Inflammatory Bowel Disease in Children

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1083
Author(s):  
Aleksandra Filimoniuk ◽  
Agnieszka Blachnio-Zabielska ◽  
Monika Imierska ◽  
Dariusz Marek Lebensztejn ◽  
Urszula Daniluk
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
High Performance ◽  
Area Under The Curve ◽  
Study Groups ◽  
Diagnostic Value ◽  
Serum Samples ◽  
Specificity And Sensitivity ◽  
Potential Biomarker ◽  
Inflammatory Bowel

An altered ceramide composition in patients with inflammatory bowel disease (IBD) has been reported recently. The aim of this study was to evaluate the concentrations of sphingolipids in the serum of treatment-naive children with newly diagnosed IBD and to determine the diagnostic value of the tested lipids in pediatric IBD. The concentrations of sphingolipids in serum samples were evaluated using a quantitative method, an ultra-high-performance liquid chromatography-tandem mass spectrometry in children with Crohn’s disease (CD) (n=34), ulcerative colitis (UC) (n = 39), and controls (Ctr) (n = 24). Among the study groups, the most significant differences in concentrations were noted for C16:0-LacCer, especially in children with CD compared to Ctr or even to UC. Additionally, the relevant increase in C20:0-Cer and C18:1-Cer concentrations were detected in both IBD groups compared to Ctr. The enhanced C24:0-Cer level was observed only in UC, while C18:0-Cer only in the CD group. The highest area under the curve (AUC), specificity, and sensitivity were determined for C16:0-LacCer in CD diagnosis. Our results suggest that the serum LacC16-Cer may be a potential biomarker that distinguishes children with IBD from healthy controls and differentiates IBD subtypes. In addition, C20:0-Cer and C18:0-Cer levels also seem to be closely connected with IBD.

scholarly journals Relationship between Plasma Trimethylamine N-Oxide Levels and Renal Dysfunction in Patients with Hypertension

2021 ◽  
pp. 1-12
Author(s):  
Jia Zhou ◽  
Dingkun Wang ◽  
Bingong Li ◽  
Xuelian Li ◽  
Xingjun Lai ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Kidney Disease ◽  
Renal Dysfunction ◽  
High Performance ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Hypertensive Patients ◽  
Ckd Stage ◽  
Liquid Chromatography Tandem Mass ◽  
The Relationship

<b><i>Introduction:</i></b> Trimethylamine N-oxide (TMAO) is a metabolite produced by gut bacteria. Although increased TMAO levels have been linked to hypertension (HTN) and chronic kidney disease (CKD) with poor prognosis, no clinical studies have directly addressed the relationship between them. In this study, we investigated the relationship between TMAO and renal dysfunction in hypertensive patients. <b><i>Methods:</i></b> We included healthy controls (<i>n</i> = 50), hypertensive patients (<i>n</i> = 46), and hypertensive patients with renal dysfunction (<i>n</i> = 143). Their blood pressure values were taken as the highest measured blood pressure. Renal function was evaluated using the estimated glomerular filtration rate. Plasma TMAO levels were measured using high-performance liquid chromatography tandem mass spectrometry. <b><i>Results:</i></b> We found significant differences in plasma TMAO levels among the 3 groups (<i>p</i> &#x3c; 0.01). The plasma TMAO of patients with HTN was significantly higher than that of healthy people, and the plasma TMAO of patients with HTN complicated by renal dysfunction was significantly higher than either of the other groups. Patients in the highest TMAO quartile were at a higher risk of developing CKD stage 5 than those in the lowest quartile. In the receiver operating characteristic curve, the area under the curve of TMAO combined with β 2-macroglobulin for predicting renal dysfunction in patients with HTN was 0.85 (95% confidence interval 0.80–0.90). <b><i>Conclusion:</i></b> An elevated TMAO level reflects higher levels of HTN and more severe renal dysfunction. TMAO, combined with β 2-macroglobulin levels, may assist in diagnosing CKD in hypertensive patients. Plasma TMAO has predictive value for early kidney disease in hypertensive patients.

scholarly journals PK/PD Analysis of Marbofloxacin by Monte Carlo Simulation against Mycoplasma agalactiae in Plasma and Milk of Lactating Goats after IV, SC and SC-Long Acting Formulations Administration

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1104
Author(s):  
Emilio Fernández-Varón ◽  
Edgar García-Romero ◽  
Juan M. Serrano-Rodríguez ◽  
Carlos M. Cárceles ◽  
Ana García-Galán ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
High Performance ◽  
Small Ruminants ◽  
Area Under The Curve ◽  
Hplc Method ◽  
Surrogate Markers ◽  
Contagious Agalactia ◽  
Lactating Goats ◽  
Long Acting

Contagious agalactia is a mycoplasmosis affecting small ruminants that have become an important issue in many countries. However, PK/PD studies of antibiotics to treat this problem in lactating goats affected by Mycoplasma (M.) agalactiae, the main CA-causing mycoplasma are almost non-existent. The aims of this study were to evaluate the plasma and milk disposition of marbofloxacin in lactating goats after intravenous (IV), subcutaneous (SC) and subcutaneous poloxamer P407 formulations with and without carboxy-methylcellulose (SC-P407-CMC and SC-P407) administration. Marbofloxacin concentrations were analysed by the High Performance Liquid Chromatography (HPLC) method. Minimum inhibitory concentrations (MIC) of M. agalactiae field isolates from mastitic goat’s milk were used to calculate surrogate markers of efficacy. Terminal half-lives of marbofloxacin after IV, SC, SC-P407 and SC-P407-CMC administration were 7.12, 6.57, 13.92 and 12.19 h in plasma, and the half-lives of elimination of marbofloxacin in milk were 7.22, 7.16, 9.30 and 7.74 h after IV, SC, SC-P407 and SC-P407-CMC administration, respectively. Marbofloxacin penetration from the blood into the milk was extensive, with Area Under the Curve (AUCmilk/AUCplasma) ratios ranged 1.04–1.23, and maximum concentrations (Cmax-milk/Cmax-plasma) ratios ranged 0.72–1.20. The PK/PD surrogate markers of efficacy fAUC24/MIC and the Monte Carlo simulation show that marbofloxacin ratio (fAUC24/MIC > 125) using a 90% of target attainment rate (TAR) need a dose regimen between 8.4 mg/kg (SC) and 11.57 mg/kg (P407CMC) and should be adequate to treat contagious agalactia in lactating goats.

scholarly journals Single-dose intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime in volunteer subjects.

1996 ◽  
Vol 40 (7) ◽  
pp. 1617-1622 ◽  
Author(s):  
J E Conte ◽  
J Golden ◽  
S Duncan ◽  
E McKenna ◽  
E Lin ◽  
...  
Keyword(s):  
Single Dose ◽  
Bronchoalveolar Lavage ◽  
Peak Concentration ◽  
Area Under The Curve ◽  
Lavage Fluid ◽  
Diffusion Method ◽  
Alveolar Cells ◽  
Epithelial Lining Fluid ◽  
Drug Concentrations ◽  
Oral Doses

The intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime were studied in 68 volunteers who received single, oral doses of azithromycin (0.5 g), clarithormycin (0.5 g), ciprofloxacin (0.5 g), or cefuroxime (0.5 g). In subgroups of four subjects each, the subjects underwent bronchoscopy and bronchoalveolar lavage at timed intervals following drug administration. Drug concentrations, including those of 14-hydroxyclarithromycin (14H), were determined in serum, bronchoalveolar lavage fluid, and alveolar cells (ACs) by high-pressure liquid chromatography. Concentrations in epithelial lining fluid (ELF) were calculated by the urea diffusion method. The maximum observed concentrations (mean +/- standard deviation) of azithromycin, clarithromycin, 14H, ciprofloxacin, and cefuroxime in serum were 0.13 +/- 0.07, 1.0 +/- 0.6, 0.60 +/- 0.41, 0.95 +/- 0.32, and 1.1 +/- 0.3 microgram/ml, respectively (all at 6 h). None of the antibiotics except clarithromycin (39.6 +/- 41.1 micrograms/ml) was detectable in ELF at the 6-h bronchoscopy. The movement into and persistence in cells was different for azithromycin and clarithromycin. In ACs azithromycin was not detectable at 6 h, reached its highest concentration at 120 h, and exhibited the greatest area under the curve (7,403 micrograms.hr ml-1). The peak concentration of clarithromycin (181 +/- 94.1 micrograms/ml) was greater and occurred earlier (6 h), but the area under the curve (2,006 micrograms.hr ml-1) was less than that observed for azithromycin. 14H was detectable in ACs at 6 h (40.3 +/- 5.2 micrograms/ml) and 12 h (32.8 +/- 57.2 micrograms/ml). The peak concentration of ciprofloxacin occurred at 6 h (4.3 +/- 5.2 micrograms/ml), and the area under the curve was 35.0 micrograms.hr ml-1. The data indicate that after the administration of a single dose, azithromycin, clarithromycin, and ciprofloxacin penetrated into ACs in therapeutic concentrations and that only clarithromycin was present in ELF. The correlation of these kinetic observations with clinical efficacy or toxicity was not investigated and is unclear, but the data provide a basis for further kinetic and clinical studies.

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