scholarly journals Inclusion Compound of Efavirenz and γ-Cyclodextrin: Solid State Studies and Effect on Solubility

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 519
Author(s):  
Susana Santos Braga ◽  
Firas El-Saleh ◽  
Karyna Lysenko ◽  
Filipe A. Almeida Paz
Keyword(s):  
Solid State ◽  
Inclusion Compound ◽  
Aqueous Solubility ◽  
Variation Method ◽  
Solid Inclusion ◽  
Antiretroviral Drug ◽  
Immunodeficiency Virus ◽  
Ft Ir ◽  
Cp Mas Nmr

Efavirenz is an antiretroviral drug of widespread use in the management of infections with human immunodeficiency virus type 1 (HIV-1). Efavirenz is also used in paediatrics, but due to its very poor aqueous solubility the liquid formulations available resort to oil-based excipients. In this report we describe the interaction of γ-cyclodextrin with efavirenz in solution and in the solid state. In aqueous solution, the preferential host–guest stoichiometry was determined by the continuous variation method using 1H NMR, which indicated a 3:2 host-to-guest proportion. Following, the solid inclusion compound was prepared at different stoichiometries by co-dissolution and freeze-drying. Solid-state characterisation of the products using FT-IR, 13C{1H} CP-MAS NMR, thermogravimetry, and X-ray powder diffraction has confirmed that the 3:2 stoichiometry is the adequate starting condition to isolate a solid inclusion compound in the pure form. The effect of γ-cyclodextrin on the solubility of efavirenz is studied by the isotherm method.

scholarly journals Solid-state studies and antioxidant properties of the γ-cyclodextrin·fisetin inclusion compound

2017 ◽  
Vol 13 ◽  
pp. 2138-2145 ◽  
Author(s):  
Joana M Pais ◽  
Maria João Barroca ◽  
Maria Paula M Marques ◽  
Filipe A Almeida Paz ◽  
Susana S Braga
Keyword(s):  
Inclusion Compound ◽  
Antioxidant Properties ◽  
Physicochemical Analysis ◽  
Water Soluble ◽  
Solid Inclusion ◽  
Human Consumption ◽  
X Ray Diffraction ◽  
Wide Range ◽  
Soluble Solid ◽  
Cp Mas Nmr

Fisetin is a natural antioxidant with a wide range of nutraceutical properties, including antidiabetic, neuroprotecting, and suppression or prevention of tumors. The present work describes the preparation of a water-soluble, solid inclusion compound of fisetin with gamma-cyclodextrin (γ-CD), a cyclic oligosaccharide approved for human consumption. A detailed physicochemical analysis of the product is carried out using elemental analysis, powder X-ray diffraction (PXRD), Raman, infrared and 13C{1H} CP-MAS NMR spectroscopies, and thermal analysis (TGA) to verify fisetin inclusion and to present a hypothetical structural arrangement for the host–guest units. The antioxidant activity of the γ-CD·fisetin inclusion compound is evaluated by the DPPH assay.

scholarly journals Pharmacokinetic Profiles of Nevirapine and Indinavir in Various Fractions of Seminal Plasma

2001 ◽  
Vol 45 (10) ◽  
pp. 2902-2907 ◽  
Author(s):  
Rieneke M. E. van Praag ◽  
Sjoerd Repping ◽  
Jan W. A. de Vries ◽  
Joep M. A. Lange ◽  
Richard M. W. Hoetelmans ◽  
...  
Keyword(s):  
Seminal Plasma ◽  
Seminal Vesicles ◽  
Sexual Abstinence ◽  
Limited Data ◽  
Dosing Interval ◽  
Drug Ingestion ◽  
Drug Concentrations ◽  
Antiretroviral Drug ◽  
Immunodeficiency Virus

ABSTRACT Limited data are available on antiretroviral drug concentrations in seminal plasma during a dosing interval. Further, since human ejaculate is composed of fluids originating from the testes, the seminal vesicles, and the prostate, all having different physiological characteristics, drug concentrations in total seminal plasma do not necessarily reflect concentrations in the separate compartments. Five human immunodeficiency virus type 1-infected patients on nevirapine (NVP; 200 mg twice a day [b.i.d.]) and/or indinavir (IDV; 800 mg b.i.d. with ritonavir, 100 mg b.i.d.) regimens used a split ejaculate technique to separate seminal plasma in two fractions, representing fluids from the testes and prostate (first fraction) and fluids from the seminal vesicles (second fraction). Split-ejaculate samples were provided at 0, 2, 5, and 8 h after drug ingestion, on separate days after 3 days of sexual abstinence. NVP and IDV showed time-dependent concentrations in seminal plasma, with peak concentrations in both fractions at 2 and 2 to 5 h, respectively, after drug ingestion. The NVP concentrations were not significantly different between the first and second fractions of the ejaculate at all time points measured and were in the therapeutic range, except for the predose concentration in two patients. The median (range) predose IDV concentrations in the first and second fractions of the ejaculate were 448 (353 to 1,015) ng/ml and 527 (240 to 849) ng/ml, respectively (P = 0.7). In conclusion, NVP and IDV concentrations in seminal plasma are dependent on the time after drug ingestion. Furthermore, our data suggest that NVP and IDV achieve therapeutic concentrations in both the testes and prostate and the seminal vesicles throughout the dosing interval.

scholarly journals High Concentrations of Nelfinavir as an Independent Risk Factor for Lipodystrophy in Human Immunodeficiency Virus-Infected Patients

2002 ◽  
Vol 46 (12) ◽  
pp. 4009-4012 ◽  
Author(s):  
Jean-Marc Tréluyer ◽  
Jean-Pierre Morini ◽  
Jérome Dimet ◽  
Isabelle Gorin ◽  
Elisabeth Rey ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Risk Factor ◽  
Independent Risk Factor ◽  
Drug Exposure ◽  
Self Report ◽  
Antiretroviral Drug ◽  
Immunodeficiency Virus ◽  
Trough Concentrations ◽  
High Concentrations

ABSTRACT To assess the relationship between antiretroviral drug exposure and lipodystrophy, 69 human immunodeficiency virus type 1-infected patients receiving nelfinavir were investigated cross-sectionally. Lipodystrophy was defined by patients' self-report. Nelfinavir trough concentrations in plasma were significantly related to overall lipodystrophy and peripheral fat wasting scores and appeared to be an independent risk factor for lipodystrophy

scholarly journals Dynamics of Human Immunodeficiency Virus Type 1 Replication in Vertically Infected Infants

1999 ◽  
Vol 73 (1) ◽  
pp. 362-367 ◽  
Author(s):  
Katherine Luzuriaga ◽  
Hulin Wu ◽  
Margaret McManus ◽  
Paula Britto ◽  
William Borkowsky ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Drug Regimen ◽  
Turnover Rates ◽  
Antiretroviral Drug ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Plasma human immunodeficiency virus type 1 (HIV-1) turnover and kinetics were studied in children aged 15 days to 2 years following the initiation of a triple antiretroviral drug regimen consisting of zidovudine, lamivudine, and nevirapine. HIV-1 turnover was at least as rapid as that previously described in adults; turnover rates were more rapid in infants and children aged 3 months to 2 years than in infants less than 3 months of age. These data confirm the central role of HIV-1 replication in the pathogenesis of vertical HIV-1 infection and reinforce the importance of early, potent combination therapies for the long-term control of HIV-1 replication.

scholarly journals Phenotypic Susceptibilities to Tenofovir in a Large Panel of Clinically Derived Human Immunodeficiency Virus Type 1 Isolates

2002 ◽  
Vol 46 (4) ◽  
pp. 1067-1072 ◽  
Author(s):  
P. R. Harrigan ◽  
M. D. Miller ◽  
P. McKenna ◽  
Z. L. Brumme ◽  
B. A. Larder
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Tenofovir Disoproxil Fumarate ◽  
Antiretroviral Drug ◽  
Immunodeficiency Virus ◽  
Large Panel ◽  
Treatment Naïve ◽  
Rt Inhibitors ◽  
Hiv 1

ABSTRACT Tenofovir is a nucleotide analogue human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitor, and its oral prodrug, tenofovir disoproxil fumarate, has recently been approved for the treatment of HIV-1 infection in the United States. The objective of this study was to characterize the in vitro susceptibility profiles of a large panel of clinically derived HIV-1 isolates for tenofovir. The distribution of tenofovir susceptibilities in over 1,000 antiretroviral-naive, HIV-1-infected individuals worldwide was determined using the Virco Antivirogram assay. In addition, phenotypic susceptibilities to tenofovir and other RT inhibitors were determined in a panel of nearly 5,000 recombinant HIV-1 clinical isolates from predominantly treatment-experienced patients analyzed as a part of routine drug resistance testing. Greater than 97.5% of isolates from treatment-naive patients had tenofovir susceptibilities <3-fold above those of the wild-type controls by the Antivirogram. The clinically derived panel of 5,000 samples exhibited a broad range of antiretroviral drug susceptibilities, including 69, 43, and 16% having >10-fold-decreased susceptibilities to at least one, two, and three antiretroviral drug classes, respectively. Greater than 88% of these 5,000 clinical isolates were within the threefold susceptibility range for tenofovir, and >99% exhibited <10-fold-reduced susceptibilities to tenofovir. Decreased susceptibility to tenofovir was not directly associated with resistance to other RT inhibitors; r 2 values of log-log linear regression plots of susceptibility to tenofovir versus susceptibility to other RT inhibitors were <0.4. The results suggest that the majority of treatment-naive and treatment-experienced individuals harbor HIV that remains within the normal range of tenofovir susceptibilities and may be susceptible to tenofovir disoproxil fumarate therapy.

scholarly journals Inhibition of Human Immunodeficiency Virus Type 1 Entry in Cells Expressing gp41-Derived Peptides

2004 ◽  
Vol 78 (2) ◽  
pp. 568-575 ◽  
Author(s):  
Marc Egelhofer ◽  
Gunda Brandenburg ◽  
Holger Martinius ◽  
Patricia Schult-Dietrich ◽  
Gregory Melikyan ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Heptad Repeat ◽  
Therapeutic Approaches ◽  
Transmembrane Glycoprotein ◽  
Antiretroviral Drug ◽  
Immunodeficiency Virus ◽  
Hiv Type 1 ◽  
Hiv 1 ◽  
Maximal Expression

ABSTRACT As the limitations of antiretroviral drug therapy, such as toxicity and resistance, become evident, interest in alternative therapeutic approaches for human immunodeficiency virus (HIV) infection is growing. We developed the first gene therapeutic strategy targeting entry of a broad range of HIV type 1 (HIV-1) variants. Infection was inhibited at the level of membrane fusion by retroviral expression of a membrane-anchored peptide derived from the second heptad repeat of the HIV-1 gp41 transmembrane glycoprotein. To achieve maximal expression and antiviral activity, the peptide itself, the scaffold for presentation of the peptide on the cell surface, and the retroviral vector backbone were optimized. This optimized construct effectively inhibited virus replication in cell lines and primary blood lymphocytes. The membrane-anchored C-peptide was also shown to bind to free gp41 N peptides, suggesting that membrane-anchored antiviral C peptides have a mode of action similar to that of free gp41 C peptides. Preclinical toxicity and efficacy studies of this antiviral vector have been completed, and clinical trials are in preparation.

Sign in / Sign up

Export Citation Format

Share Document