The percutaneous absorption and skin distribution of lindane in man

1997 ◽  
Vol 16 (11) ◽  
pp. 645-651 ◽  
Author(s):  
Ian P Dick ◽  
Peter G Blain ◽  
Faith M Williams
Keyword(s):  
Stratum Corneum ◽  
Percutaneous Absorption ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Systemic Circulation ◽  
White Spirit ◽  
Application Site ◽  
Small Areas ◽  
Exposure Site ◽  
Applied Dose

1 The absorption and distribution of lindane through skin was examined using human volunteers. Two different preparations were employed, one with acetone as the vehicle and the other, a commercial product, consisting primarily of white spirit as the solvent base. 2 The mean peak plasma concentrations of lindane following exposure to the acetone and white-spirit based applications were 0.91 and 0.47 ng/ml, respec tively. The similarity between these levels did not reflect the 40-fold higher dose of lindane in the acetone vehicle. White spirit enhanced the penetration of lindane with respect to the acetone vehicle, high lighting the influence of vehicle upon percutaneous absorption. Low levels of trichlorophenol glucuronide metabolites, but no lindane, were detected in the urine. 3 The exposure site was washed at 6 h to mimic a decontamination procedure at the end of a working day. The proportion of the applied dose unabsorbed by 6 h was 80% and 10% for the acetone and the white spirit-based formulation, respectively. Small areas of the exposed site were tape stripped at 6 and 24 h to assess any lindane that may be associated with the stratum corneum. High levels were observed in the stratum corneum at 6 h exposure (up to 30% of the applied dose for the white spirit based formulation). However, this level had decreased by 24 h (by at least 90% of the amount found at 6 h). A gauze or gauze/shirt combination covering the application site between 6 and 24 h did account for some of this loss of lindane from the stratum corneum attributed to friction and removal of exfoliated cells. The unaccounted propor tion was presumed to have been absorbed through the skin into the systemic circulation. This demonstrates the absorption of chemicals can occur from a depot in the stratum corneum even following a wash proce dure.

The percutaneous absorption and skin distribution of lindane in man

1997 ◽  
Vol 16 (11) ◽  
pp. 652-657 ◽  
Author(s):  
Ian P Dick ◽  
Peter G Blain ◽  
Faith M Williams
Keyword(s):  
Stratum Corneum ◽  
Percutaneous Absorption ◽  
Aqueous Ethanol ◽  
Skin Surface ◽  
Acetone Solution ◽  
White Spirit ◽  
Strong Indication ◽  
Applied Dose

1 The absorption of lindane through human skin was assessed in vitro using static diffusion cells with 50% aqueous ethanol as the receptor fluid. Four formula tions of lindane were applied, three of which were commercial preparations. The dermal distribution of lindane within the skin was also examined, focusing particularly on any association of lindane to the stratum corneum. The results were then compared with a parellel in vivo study. 2 Two of the formulations contained white spirit as the predominant solvent, and lindane absorption was greatest from these preparations in terms of the percentage of the applied dose (15-25% by 24 h). Absorption was less from an aqueous spray dilution (3% by 24 h), with absorption from acetone being the least ( < 1% by 24 h). Similar amounts of lindane penetrated by 24 h for the acetone and white spirit- based applications (approx. 8 ?g). This supported the in vivo observation that similar plasma lindane levels were recorded following exposure to the acetone solution and the white spirit-based formulation A, although the lindane concentration in acetone was 40- fold higher. 3 For the acetone and water-based preparations, a soap/ water swab of the skin surface at 6 h contained the majority of the applied dose (around 75%). Substantial amounts of lindane were recovered in tape-strippings taken at 6 h (representative of stratum corneum content) which were significantly greater than lindane in the remainder of the skin, for the acetone solution and formulation A. This provided a strong indication that lindane had accumulated in the stratum corneum, a property that has been linked with other lipophilic chemicals.

Comparative Plasma Heparin Levels after Subcutaneous Sodium and Calcium Heparin

1978 ◽  
Vol 40 (02) ◽  
pp. 397-406 ◽  
Author(s):  
Joyce Low ◽  
J C Biggs
Keyword(s):  
Peak Plasma ◽  
Plasma Concentrations ◽  
Factor Xa ◽  
Normal Subjects ◽  
Sodium Salts ◽  
Sodium Heparin ◽  
Significant Difference ◽  
Heparin Plasma ◽  
Calcium Heparin ◽  
Plasma Heparin

SummaryComparative plasma heparin levels were measured in normal subjects injected subcutaneously with 5,000 units of the sodium and calcium salts of heparin. Plasma heparin levels were measured up to 7 hr post-injection by an anti-factor Xa assay (Denson and Bonnar 1973). Preliminary studies indicated that heparin levels were reproducible in subjects who received two injections of the same heparin. Peak plasma concentrations (Cmax) and the time at which peak concentration was reached (Tmax) varied greatly from subject to subject. In one group of subjects (15) two commonly used heparins, a sodium heparin (Evans) and a calcium heparin (Choay) were compared. Peak heparin concentrations were not significantly different. However the Tmax for the sodium heparin (1.5 hr) was significantly earlier than the Tmax for the calcium heparin (3 hr) and this was not due to a difference in the volume of the two heparin injections. No significant difference could be detected in the plasma clearance rate and the molecular weight distribution of the two heparins.In two other groups of subjects, sodium and calcium preparations from two manufacturers were compared. In general, the sodium salts gave rise to significantly higher plasma concentrations, which could be interpreted as a greater bioavailability of sodium salts. These results indicate that the salt of the heparin can influence the plasma concentration achieved after subcutaneous injection.

Bioavailability in Rats of Human Recombinant Tissue Plasminogen Activator After Subcutaneous and Intramuscular Injection

1986 ◽  
Vol 56 (03) ◽  
pp. 299-301 ◽  
Author(s):  
L J Garcia Frade ◽  
S Poole ◽  
S Hanley ◽  
L J Creighton ◽  
A D Curtis ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Inferior Vena ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Vena Cava ◽  
Recombinant Tissue Plasminogen Activator ◽  
Fibrin Plate ◽  
Tissue Plasminogen

SummaryThe bioavailability of human recombinant tissue plasminogen activator (rt-PA) in rats was measured after subcutaneous (s.c.) and intramuscular (i.m.) injection. Rt-PA was absorbed after both i.m. and s.c. injection, giving peak plasma concentrations within 30 min and 1 h, respectively, with detectable concentrations up to 6 h. These peak values of bioavailable t-PA were obtained in a functional fibrin plate assay of euglobulin precipitates and expressed as +88% and +243% (for s.c. and i.m. routes respectively) above basal rat fibrinolytic activity. Prior injection of rt-PA, s.c. or i.m., significantly reduced the weights of thrombi induced in the inferior vena cava after injection.

scholarly journals Identification of Anti-Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Oxysterol Derivatives In Vitro

2021 ◽  
Vol 22 (6) ◽  
pp. 3163
Author(s):  
Hirofumi Ohashi ◽  
Feng Wang ◽  
Frank Stappenbeck ◽  
Kana Tsuchimoto ◽  
Chisa Kobayashi ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Replication ◽  
Cultured Cells ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Membrane Vesicles ◽  
Drug Candidates ◽  
Increased Risk ◽  
Derivatives Of

The development of effective antiviral drugs targeting the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is urgently needed to combat the coronavirus disease 2019 (COVID-19). We have previously studied the use of semi-synthetic derivatives of oxysterols, oxidized derivatives of cholesterol as drug candidates for the inhibition of cancer, fibrosis, and bone regeneration. In this study, we screened a panel of naturally occurring and semi-synthetic oxysterols for anti-SARS-CoV-2 activity using a cell culture infection assay. We show that the natural oxysterols, 7-ketocholesterol, 22(R)-hydroxycholesterol, 24(S)-hydroxycholesterol, and 27-hydroxycholesterol, substantially inhibited SARS-CoV-2 propagation in cultured cells. Among semi-synthetic oxysterols, Oxy210 and Oxy232 displayed more robust anti-SARS-CoV-2 activities, reducing viral replication more than 90% at 10 μM and 99% at 15 μM, respectively. When orally administered in mice, peak plasma concentrations of Oxy210 fell into a therapeutically relevant range (19 μM), based on the dose-dependent curve for antiviral activity in our cell-based assay. Mechanistic studies suggest that Oxy210 reduced replication of SARS-CoV-2 by disrupting the formation of double-membrane vesicles (DMVs); intracellular membrane compartments associated with viral replication. Our study warrants further evaluation of Oxy210 and Oxy232 as a safe and reliable oral medication, which could help protect vulnerable populations with increased risk of developing COVID-19.

scholarly journals Human Endotoxemia Induces Down-Regulation of Monocyte CC Chemokine Receptor 2

2006 ◽  
Vol 13 (1) ◽  
pp. 156-159 ◽  
Author(s):  
Michael Heesen ◽  
Rosemarijn Renckens ◽  
Alex F. de Vos ◽  
Dagmar Kunz ◽  
Tom van der Poll
Keyword(s):  
Chemokine Receptor ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Necrosis Factor Alpha ◽  
Human Endotoxemia ◽  
Cc Chemokine ◽  
Chemotactic Protein ◽  
Human Volunteers ◽  
Cc Chemokine Receptor 2 ◽  
Factor Alpha

ABSTRACT Upon injection of Escherichia coli lipopolysaccharide into human volunteers, the monocyte density of CC chemokine receptor 2 (CCR2) decreased. Minimal CCR2 density was observed 4 h after injection. Peak plasma concentrations of the CCR2 ligand monocyte chemotactic protein 1 and of tumor necrosis factor alpha were reached after 4 h and 2 h, respectively.

Single-dose pharmacokinetics of orally administered terbinafine in bearded dragons (Pogona vitticeps) and the antifungal susceptibility patterns of Nannizziopsis guarroi

2021 ◽  
pp. 1-8
Author(s):  
Michael S. McEntire ◽  
Jennifer M. Reinhart ◽  
Sherry K. Cox ◽  
Krista A. Keller
Keyword(s):  
Single Dose ◽  
High Performance ◽  
Clinical Decision Making ◽  
Peak Plasma ◽  
Antifungal Susceptibility ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
Oral Solution ◽  
Susceptibility Data ◽  
Pogona Vitticeps

Abstract OBJECTIVE To identify the antifungal susceptibility of Nanniziopsis guarroi isolates and to evaluate the single-dose pharmacokinetics of orally administered terbinafine in bearded dragons. ANIMALS 8 healthy adult bearded dragons. PROCEDURES 4 isolates of N guarroi were tested for antifungal susceptibility. A compounded oral solution of terbinafine (25 mg/mL [20 mg/kg]) was given before blood (0.2 mL) was drawn from the ventral tail vein at 0, 4, 8, 12, 24, 48, 72, and 96 hours after administration. Plasma terbinafine concentrations were measured with high-performance liquid chromatography. RESULTS The antifungal minimum inhibitory concentrations against N guarroi isolates ranged from 4,000 to > 64,000 ng/mL for fluconazole, 125 to 2,000 ng/mL for itraconazole, 125 to 2,000 ng/mL for ketoconazole, 125 to 1,000 ng/mL for posaconazole, 60 to 250 ng/mL for voriconazole, and 15 to 30 ng/mL for terbinafine. The mean ± SD peak plasma terbinafine concentration in bearded dragons was 435 ± 338 ng/mL at 13 ± 4.66 hours after administration. Plasma concentrations remained > 30 ng/mL for > 24 hours in all bearded dragons and for > 48 hours in 6 of 8 bearded dragons. Mean ± SD terminal half-life following oral administration was 21.2 ± 12.40 hours. CLINICAL RELEVANCE Antifungal susceptibility data are available for use in clinical decision making. Results indicated that administration of terbinafine (20 mg/kg, PO, q 24 to 48 h) in bearded dragons may be appropriate for the treatment of dermatomycoses caused by N guarroi. Clinical studies are needed to determine the efficacy of such treatment.

scholarly journals Plasma and tissue clindamycin antimicrobial activity after parenteral administration to cats under surgical conditions

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Sabrina Passini ◽  
Laura Montoya ◽  
Martín Lupi ◽  
Paula Lorenzini ◽  
María Fabiana Landoni ◽  
...  
Keyword(s):  
Peak Plasma ◽  
Subcutaneous Tissue ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Dose Interval ◽  
Tissue Concentrations ◽  
Administration Routes ◽  
Infection Treatment ◽  
Plasma Concentration Ratio ◽  
Surgical Conditions

Clindamycin plasma and tissue disposition in cats under surgical conditions after a single intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration at a dose rate of 10 mg/kg were studied. After intravenous, intramuscular and subcutaneous administration, peak plasma concentrations were 10.93±3.78 μg/mL (Cp(0)), 5.93±1.18 μg/mL (Cmax)) and 6.30±0.88 μg/mL (Cmax)), respectively. Eight hours after clindamycin IV, IM and SC administration plasma concentrations declined to 2.01±0.61 μg/mL, 2.96±0.43 μg/mL and 3.36±0.97 μg/mL, respectively. Sixty to 90 minutes after clindamycin administration, tissue concentrations ranged from a minimum in subcutaneous tissue of 4.90 μg/g (IV), 3.06 μg/g (IM) and, 3.13 μg/g (SC) to a maximum in uterus of 13.41 μg/g (IV), 14.07 μg/g (IM) and, 14.44 μg/g (SC). The lowest tissue/plasma concentration ratio for the three administration routes was observed in subcutaneous tissue, while the highest was observed at genital level (ovary for IV and IM and uterus for SC). Estimated efficacy predictor (AUC/MIC), considering MIC breakpoint for bacteria isolated from animals, indicates that clindamycin administered IV, IM or SC at the studied dose is appropriated for perioperative prophylactic protocols and that given with a dose interval of 12 hours would be effective for susceptible infection treatment in cats.

scholarly journals Pharmacokinetics of Buprenorphine Hydrochloride (BN HCl). (2): Role of Stratum Corneum in Percutaneous Absorption of TSN-09 (BN HCl containing tape) in Male Rats.

2001 ◽  
Vol 16 (6) ◽  
pp. 584-589
Author(s):  
Yasuhiro TAKAHASHI ◽  
Shigeyuki ISHII ◽  
Hironori ARIZONO ◽  
Shin-ichi NISHIMURA ◽  
Noriyuki SAITO ◽  
...  
Keyword(s):  
Stratum Corneum ◽  
Percutaneous Absorption ◽  
Male Rats

scholarly journals Development of Ethosomal Gel from Withania Somnifera

2020 ◽  
Vol 4 (2) ◽  
Keyword(s):  
Drug Delivery ◽  
Stratum Corneum ◽  
Patient Compliance ◽  
Drug Delivery Systems ◽  
Withania Somnifera ◽  
Systemic Circulation ◽  
Cellular Communication ◽  
Cost Of Treatment ◽  
Total Cost ◽  
Novel Drug

Novel drug delivery systems are used to increase administration of drugs through transdermal system. Ethosomes has the ability to permeate through the stratum corneum. Ethosomes are the delivery carriers that enable the drugs to reach the deep skin layers as well as the systemic circulation. These vesicles are well known for their importance in cellular communication and in particle transportation for many years. This article reviews various aspects of ethosomes which includes their preparation, characterization, advantages and their applications in drug delivery. Ethosomes has number of important benefits such as, it improves the drug’s efficacy, enhances the patient compliance, comfort and reduces the total cost of treatment.

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