Effects of a P-Glycoprotein Inhibitor on Brain and Plasma Concentrations of Anti-Human Immunodeficiency Virus Drugs Administered in Combination in Rats

2002 ◽  
Vol 30 (5) ◽  
pp. 479-482 ◽  
Author(s):  
Jouko Savolainen ◽  
Jeffrey E. Edwards ◽  
Michael E. Morgan ◽  
Patrick J. McNamara ◽  
Bradley D. Anderson
Keyword(s):  
Human Immunodeficiency Virus ◽  
Plasma Concentrations ◽  
P Glycoprotein ◽  
Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Drugs

The acute-phase protein response to human immunodeficiency virus infection in human subjects

1999 ◽  
Vol 276 (6) ◽  
pp. E1092-E1098 ◽  
Author(s):  
Farook Jahoor ◽  
Brian Gazzard ◽  
Gary Phillips ◽  
Danny Sharpstone ◽  
Melanie Delrosario ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Infection ◽  
Human Immunodeficiency Virus Infection ◽  
Acute Phase ◽  
Protein Turnover ◽  
Plasma Concentrations ◽  
Retinol Binding Protein ◽  
Whole Body ◽  
Body Protein ◽  
Immunodeficiency Virus

Although several studies have shown that asymptomatic human immunodeficiency virus infection elicits an increase in whole body protein turnover, it is not known whether this increased protein turnover includes changes in the kinetics of acute-phase proteins (APPs). To answer this question, we measured 1) the plasma concentrations of four positive (C-reactive protein, α1-antitrypsin, haptoglobin, and fibrinogen) and four negative APPs [albumin, high-density lipoprotein (HDL)-apolipoprotein (apo) A1, transthyretin, and retinol-binding protein] and 2) the fractional (FSR) and absolute (ASRs) synthesis rates of three positive and three negative APPs using a constant intravenous infusion of [2H5]phenylalanine in five subjects with symptom-free acquired immunodeficiency syndrome (AIDS) and five noninfected control subjects. Compared with the values of the controls, the plasma concentrations, FSRs, and ASRs of most positive APPs were higher in the AIDS group. The negative APPs had faster FSRs in the AIDS group, there was no difference between the ASRs of the two groups, and only HDL-apoA1 had a lower plasma concentration. These results suggest that symptom-free AIDS elicits an APP response that is different from bacterial infections, as the higher concentrations and faster rates of synthesis of the positive APPs are not accompanied by lower concentrations and slower rates of synthesis of most of the negative APPs.

scholarly journals Small Bowel Review - Part I

1997 ◽  
Vol 11 (1) ◽  
pp. 49-56 ◽  
Author(s):  
ABR Thomson ◽  
E Jarocka-Cyrta ◽  
J Faria ◽  
GE Wild
Keyword(s):  
Human Immunodeficiency Virus ◽  
Small Bowel ◽  
Early Development ◽  
Intestinal Infections ◽  
Immunodeficiency Virus ◽  
Proliferation And Differentiation ◽  
Nucleotides And Nucleosides ◽  
Gastrointestinal Peptides ◽  
Human Immunodeficiency Virus Drugs ◽  
Mucosal Proliferation

The small bowel has undergone intense study. Part I of this two-part review of the small bowel focuses on gastrointestinal peptides; intestinal infections and human immunodeficiency virus; drugs; intestinal growth - mucosal proliferation and differentiation; nucleic acids, nucleotides and nucleosides; vitamins and minerals; Whipple's disease; radiation; and early development.

Hepatitis B virus and human immunodeficiency virus drugs in pregnancy: Findings from the Antiretroviral Pregnancy Registry

2012 ◽  
Vol 57 (5) ◽  
pp. 953-959 ◽  
Author(s):  
Robert S. Brown ◽  
Elizabeth C. Verna ◽  
Marcus R. Pereira ◽  
Hugh H. Tilson ◽  
Christopher Aguilar ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Drugs ◽  
Pregnancy Registry ◽  
In Pregnancy

scholarly journals Is the Recommended Dose of Efavirenz Optimal in Young West African Human Immunodeficiency Virus-Infected Children?

2009 ◽  
Vol 53 (10) ◽  
pp. 4407-4413 ◽  
Author(s):  
Déborah Hirt ◽  
Saik Urien ◽  
Mathieu Olivier ◽  
Hélène Peyrière ◽  
Boubacar Nacro ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Body Weight ◽  
Plasma Concentrations ◽  
Individual Characteristics ◽  
Population Pharmacokinetic ◽  
Ratio Test ◽  
Time Curve ◽  
Once Daily ◽  
Concentration Time ◽  
Immunodeficiency Virus

ABSTRACT We aimed in this study to describe efavirenz concentration-time courses in treatment-naïve children after once-daily administration to study the effects of age and body weight on efavirenz pharmacokinetics and to test relationships between doses, plasma concentrations, and efficacy. For this purpose, efavirenz concentrations in 48 children were measured after 2 weeks of didanosine-lamivudine-efavirenz treatment, and samples were available for 9/48 children between months 2 and 5 of treatment. Efavirenz concentrations in 200 plasma specimens were measured using a validated high-performance liquid chromatography method. A population pharmacokinetic model was developed with NONMEM. The influence of individual characteristics was tested using a likelihood ratio test. The estimated minimal and maximal concentrations of efavirenz in plasma (C min and C max, respectively) and the area under the concentration-time curve (AUC) were correlated to the decrease in human immunodeficiency virus type 1 RNA levels after 3 months of treatment. The threshold C min (and AUC) that improved efficacy was determined. The target minimal concentration of 4 mg/liter was considered for toxicity. An optimized dosing schedule that would place the highest percentage of children in the interval of effective and nontoxic concentrations was simulated. The pharmacokinetics of efavirenz was best described by a one-compartment model with first-order absorption and elimination. The mean apparent clearance and volume of distribution for efavirenz were 0.211 liter/h/kg and 4.48 liters/kg, respectively. Clearance decreased significantly with age. When the recommended doses were given to 46 of the 48 children, 19% (44% of children weighing less than 15 kg) had C mins below 1 mg/liter. A significantly higher percentage of children with C mins of >1.1 mg/liter or AUCs of >51 mg/liter·h than of children with lower values had viral load decreases greater than 2 log10 copies/ml after 3 months of treatment. Therefore, to optimize the percentage of children with C mins between 1.1 and 4 mg/liter, children should receive the following once-daily efavirenz doses: 25 mg/kg of body weight from 2 to 6 years, 15 mg/kg from 6 to 10 years, and 10 mg/kg from 10 to 15 years. These assumptions should be prospectively confirmed.

scholarly journals A Novel Nonnucleoside Analogue That Inhibits Human Immunodeficiency Virus Type 1 Isolates Resistant to Current Nonnucleoside Reverse Transcriptase Inhibitors

2006 ◽  
Vol 51 (2) ◽  
pp. 429-437 ◽  
Author(s):  
Zhijun Zhang ◽  
Wen Xu ◽  
Yung-Hyo Koh ◽  
Jae Hoon Shim ◽  
Jean-Luc Girardet ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Plasma Concentrations ◽  
Cross Resistance ◽  
Double Mutation ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are important components of current combination therapies for human immunodeficiency virus type 1 (HIV-1) infection. However, their low genetic barriers against resistance development, cross-resistance, and serious side effects can compromise the benefits of the two current drugs in this class (efavirenz and nevirapine). In this study, we report a novel and potent NNRTI, VRX-480773, that inhibits viruses from efavirenz-resistant molecular clones and most NNRTI-resistant clinical HIV-1 isolates tested. In vitro mutation selection experiments revealed that longer times were required for viruses to develop resistance to VRX-480773 than to efavirenz. RT mutations selected by VRX-480773 after 3 months of cell culture in the presence of 1 nM VRX-480773 carried the Y181C mutation, resulting in a less-than-twofold increase in resistance to the compound. A virus containing the double mutation V106I-Y181C emerged after 4 months, causing a sixfold increase in resistance. Viruses containing additional mutations of D123G, F227L, and T369I emerged when the cultures were incubated with increasing concentrations of VRX-480773. Most of the resistant viruses selected by VRX-480773 are susceptible to efavirenz. Oral administration of VRX-480773 to dogs resulted in plasma concentrations that were significantly higher than those required for the inhibition of wild-type and mutant viruses. These results warrant further clinical development of VRX-480773 for the treatment of HIV infection in both NNRTI-naive and -experienced patients.

scholarly journals Association of Saquinavir Plasma Concentrations with Side Effects but Not with Antiretroviral Outcome in Patients Infected with Protease Inhibitor-Susceptible Human Immunodeficiency Virus Type 1

2007 ◽  
Vol 51 (9) ◽  
pp. 3264-3272 ◽  
Author(s):  
Jörn Lötsch ◽  
Sebastian Harder ◽  
Martin Stürmer ◽  
Hans-Wilhelm Doerr ◽  
Gerd Geisslinger ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Side Effects ◽  
Protease Inhibitor ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Plasma Concentrations ◽  
Cd4 Counts ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The objective of this study was to identify parameters among saquinavir pharmacokinetics, patients' demographics or comedications, to be addressed for improved personalized therapy. The presence of human immunodeficiency virus type 1 (HIV-1) RNA at therapy week 48 (principal target parameter), CD4 cell count at week 48, infections and side effects during 48 weeks, indicators of liver toxicity and lipid abnormalities at week 48, and a 12-h saquinavir plasma concentration-versus-time profile were assessed in 56 patients receiving saquinavir-ritonavir (1,000 and 100 mg, respectively) twice daily (44 therapy-naïve and 12 antiretrovirally pretreated patients) for association with saquinavir plasma concentrations, demographics, baseline values of target parameters, and coadministered antiretrovirals. Antiretroviral failure was observed in 8 of the 56 patients in whom HIV-1 RNA was detectable at week 48. This therapeutic failure was not associated with individual saquinavir pharmacokinetics. More likely, therapeutic failure was related to incidences interfering with antiretroviral therapy, causing therapy interruptions or incompliance. Weak associations were, however, seen between high maximum saquinavir plasma concentrations and both CD4 counts of ≥200 cells μl−1 at week 48 (P = 0.014) and constitutional side effects during 48 weeks (P = 0.002). However, patients with high CD4 counts and constitutional side effects were not identical (P = 0.53). Saquinavir therapeutic drug monitoring in patients infected with protease inhibitor-susceptible HIV-1 taking saquinavir-ritonavir (1,000 and 100 mg, respectively) is not demanded for improving the antiretroviral effect. It may be contemplated in cases with constitutional side effects or low CD4 counts with weak immune responses.

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