scholarly journals Lack of effect of concomitant zidovudine on rifabutin kinetics in patients with AIDS-related complex.

1996 ◽  
Vol 40 (6) ◽  
pp. 1397-1402 ◽  
Author(s):  
R C Li ◽  
S Nightingale ◽  
R C Lewis ◽  
D C Colborn ◽  
P K Narang
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Plasma Concentrations ◽  
Urinary Recovery ◽  
Immunodeficiency Virus ◽  
Aids Related Complex ◽  
Safety Parameters ◽  
The Mean ◽  
Interval Ratio ◽  
Related Complex

The effect of concomitant dosing with the antiretroviral agent zidovudine (ZDV) on the pharmacokinetics of rifabutin (RBT) was investigated under steady-state conditions. Sixteen human immunodeficiency virus-positive patients with AIDS-related complex who had been maintained on stable ZDV therapy for > or = 6 weeks were administered RBT concomitantly for 12 days. Eight patients received daily doses of 300 or 450 mg of RBT. Administration of ZDV was discontinued on day 13, and RBT was given alone for 3 additional days. Four patients receiving 450 mg of RBT discontinued treatment. Under steady-state ZDV and RBT dosing, safety and kinetics assessments were performed on day 13 (ZDV plus RBT) and day 16 (RBT alone). Kinetics on days 13 and 16 demonstrated that RBT (300 or 450 mg) was readily absorbed, with the time at which the plasma concentration was maximal (Tmax) ranging between 2.6 and 2.9 h. At these two doses, the mean steady-state maximal plasma concentrations (Cmax) were 250 and 430 ng/ml on day 13 and 245 and 458 ng/ml on day 16, respectively. RBT kinetics at the two doses were proportional and similar on the basis of estimates of the ratios of the areas under the concentration-time curves over the dosing interval from 0 to 24 h (AUC0-24) (450 mg/300 mg), which were 1.5 and 1.4 for days 13 and 16, respectively. No significant differences were apparent in the mean oral clearance (CLs/F) estimates (range, 1.60 to 1.77 liters/h/kg), which were dose independent and similar for the 2 assessment days, as was the urinary recovery of RBT and its 25-deacetyl metabolite. Low urinary recovery of 25-deacetyl RBT and an AUC metabolite/parent ratio of 0.1 suggest that there is minimal metabolism of RBT via the deacetylation pathway. For RBT, pooled mean (95% confidence interval) ratio (day 13/day 16) estimates for Cmax, Tmax, AUC0-24, and CLs/F were 1.07 (range, 0.77 to 1.38), 1.08 (0.89 to 1.27), 0.97 (0.82 to 1.13), and 1.09 (0.92 to 1.26), respectively. In addition, no significant changes in any of the major safety parameters were detected throughout the study. Therefore, it is concluded that coadministration of ZDV and RBT does not affect the pharmacokinetics and/or safety of RBT in human immunodeficiency virus-positive patients.

scholarly journals Steady-State Pharmacokinetics of Amprenavir Coadministered with Ritonavir in Human Immunodeficiency Virus Type 1-Infected Patients

2003 ◽  
Vol 47 (1) ◽  
pp. 118-123 ◽  
Author(s):  
Cecile Goujard ◽  
Isabelle Vincent ◽  
Jean-Luc Meynard ◽  
Nathalie Choudet ◽  
Diane Bollens ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Time Curve ◽  
Concentration Time ◽  
Immunodeficiency Virus ◽  
The Mean ◽  
Hiv 1

ABSTRACT The protease inhibitor (PI) ritonavir is used as a strong inhibitor of cytochrome P450 3A4, which boosts the activities of coadministered PIs, resulting in augmented plasma PI levels, simplification of the dosage regimen, and better efficacy against resistant viruses. The objectives of the present open-label, multiple-dose study were to determine the steady-state pharmacokinetics of amprenavir administered at 600 mg twice daily (BID) and ritonavir administered at 100 mg BID in human immunodeficiency virus type 1 (HIV-1)-infected adults treated with different antiretroviral combinations including or not including a nonnucleoside reverse transcriptase inhibitor (NNRTI). Nineteen patients completed the study. The steady-state mean minimum plasma amprenavir concentration (C min,ss) was 1.92 μg/ml for patients who received amprenavir and ritonavir without an NNRTI and 1.36 μg/ml for patients who received amprenavir and ritonavir plus efavirenz. For patients who received amprenavir-ritonavir without an NNRTI, the steady-state mean peak plasma amprenavir concentration (C max,ss) was 7.12 μg/ml, the area under the concentration-time curve from 0 to 10 h (AUC0-10) was 32.06 μg · h/ml, and the area under the concentration-time curve over a dosing interval (12 h) at steady-state (AUCss) was 35.74 μg · h/ml. Decreases in the mean values of C min,ss (29%), C max,ss (42%), AUC0-10 (42%), and AUCss (40%) for amprenavir occurred when efavirenz was coadministered with amprenavir-ritonavir. No unexpected side effects were observed. As expected, coadministration of amprenavir with ritonavir resulted in an amprenavir C min,ss markedly higher than those previously reported for the marketed dose of amprenavir. When amprenavir-ritonavir was coadministered with efavirenz, amprenavir-ritonavir maintained a mean amprenavir C min,ss above the mean 50% inhibitory concentration of amprenavir previously determined for both wild-type HIV-1 isolates and HIV-1 strains isolated from PI-experienced patients. These data support the use of low-dose ritonavir to enhance the level of exposure to amprenavir and increase the efficacy of amprenavir.

scholarly journals Pharmacokinetic Study of Human Immunodeficiency Virus Protease Inhibitors Used in Combination with Amprenavir

2001 ◽  
Vol 45 (12) ◽  
pp. 3663-3668 ◽  
Author(s):  
Brian M. Sadler ◽  
Catherine Gillotin ◽  
Yu Lou ◽  
Joseph J. Eron ◽  
William Lang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Protease Inhibitors ◽  
Pharmacokinetic Study ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Immunodeficiency Virus

ABSTRACT In an open-label, randomized, multicenter, multiple-dose pharmacokinetic study, we determined the steady-state pharmacokinetics of amprenavir with and without coadministration of indinavir, nelfinavir, or saquinavir soft gel formulation in 31 human immunodeficiency virus type 1-infected subjects. The results indicated that amprenavir plasma concentrations were decreased by saquinavir soft gel capsule (by 32% for area under the concentration-time curve at steady state [AUCss] and 37% for peak plasma concentration at steady state [C max,ss]) and increased by indinavir (33% for AUCss). Nelfinavir significantly increased amprenavir minimum drug concentration at steady state (by 189%) but did not affect amprenavir AUCss orC max,ss. Nelfinavir and saquinavir steady-state pharmacokinetics were unchanged by coadministration with amprenavir compared with the historical monotherapy data. Concentrations of indinavir, coadministered with amprenavir, in plasma decreased in both single-dose and steady-state evaluations. The changes in amprenavir steady-state pharmacokinetic parameters, relative to those for amprenavir alone, were not consistent among protease inhibitors, nor were the changes consistent with potential interactions in CYP3A4 metabolism or P-glycoprotein transport. No dose adjustment of either protease inhibitor in any of the combinations studied is needed.

scholarly journals Switch from Enfuvirtide to Raltegravir Lowers Plasma Concentrations of Darunavir and Tipranavir: a Pharmacokinetic Substudy of the EASIER-ANRS 138 Trial

2011 ◽  
Vol 55 (7) ◽  
pp. 3613-3615 ◽  
Author(s):  
Lauriane Goldwirt ◽  
Joséphine Braun ◽  
Nathalie de Castro ◽  
Isabelle Charreau ◽  
Aurélie Barrail-Tran ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Time Curve ◽  
Concentration Time ◽  
Background Regimen ◽  
Immunodeficiency Virus ◽  
Plasma Concentration Time Curve

ABSTRACTWe compared tipranavir and darunavir concentrations measured at steady state in 20 human immunodeficiency virus (HIV)-infected patients enrolled in the EASIER-ANRS 138 clinical trial who switched from enfuvirtide to raltegravir while maintaining the same background regimen. The geometric mean ratios of the observed predose concentration (Ctrough), maximum concentration of drug observed in plasma (Cmax), and area under the plasma concentration-time curve (AUC) before (day 0) and after (week 24) the switch were 0.49, 0.76, and 0.67 and 0.82, 0.68, and 0.64 for tipranavir and darunavir, respectively. The virologic consequences of these drug interactions have yet to be determined.

Neurologic Manifestations of Human Immunodeficiency Virus Infection in Children

PEDIATRICS ◽  
1986 ◽  
Vol 78 (4) ◽  
pp. 678-687
Author(s):  
Leon G. Epstein ◽  
Leroy R. Sharer ◽  
James M. Oleske ◽  
Edward M. Connor ◽  
Jaap Goudsmit ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Neutralizing Antibodies ◽  
Fatal Outcome ◽  
Perinatal Period ◽  
Neurologic Manifestations ◽  
Progressive Encephalopathy ◽  
Immunodeficiency Virus ◽  
Aids Related Complex ◽  
Related Complex

This report describes the neurologic manifestations of 36 children with human immunodeficiency virus (HIV) infection. In this cohort, in 16 of 21 children with acquired immunodeficiency syndrome (AIDS), three of 12 children with AIDS-related complex, and one of three asymptomatic seropositive children, a progressive encephalopathy developed. Neurologic signs were often detected early but tended to worsen coincident with progression of the immunodeficiency. The presence of progressive encephalopathy correlated with the absence of serum neutralizing antibodies to HIV and with a poor, usually fatal, outcome. The incubation period from initial HIV infection in the perinatal period to the onset of progressive encephalopathy varied from 2 months to 5 years. Intrablood-brain barrier synthesis of HIV-specific antibodies was demonstrated in eight of 14 children with AIDS and AIDS-related complex, indicating active brain infection with HIV. In three cases this was unassociated with progressive neurologic signs. Unique neuropathologic findings in children who died with HIV infection further suggest that the progressive encephalopathy is the result of primary and persistent infection of the brain with this retrovirus. These findings broaden the spectrum of HIV infection in children and have important implications for the development of antiviral therapy.

scholarly journals Pharmacokinetics of Azithromycin Administered Alone and with Atovaquone in Human Immunodeficiency Virus-Infected Children

1999 ◽  
Vol 43 (6) ◽  
pp. 1516-1519 ◽  
Author(s):  
Leock Y. Ngo ◽  
Ram Yogev ◽  
Wayne M. Dankner ◽  
Walter T. Hughes ◽  
Sandra Burchett ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Concentration Time ◽  
Significant Difference ◽  
Immunodeficiency Virus ◽  
The Mean ◽  
Clinically Significant ◽  
To Receive

ABSTRACT To evaluate if atovaquone (ATQ) interacts pharmacokinetically with azithromycin (AZ) in human immunodeficiency virus-infected children, 10 subjects (ages, 4 to 13 years) were randomized in a crossover study to receive AZ (5 mg/kg/day) alone (ALONE) or AZ (5 mg/kg/day) and ATQ (30 mg/kg/day) simultaneously (SIM) prior to receiving AZ and ATQ staggered by 12 h. Despite a lack of significant difference in the mean AZ pharmacokinetic parameters, the steady-state values of AZ’s area under the concentration-time curve from 0 to 24 h and maximum concentration in serum were consistently lower (n = 7 of 7) for the SIM regimen than they were for the ALONE regimen. A larger study will be required to determine if ATQ affects AZ pharmacokinetics and efficacy in a clinically significant manner.

scholarly journals Zidovudine, trimethoprim, and dapsone pharmacokinetic interactions in patients with human immunodeficiency virus infection.

1996 ◽  
Vol 40 (5) ◽  
pp. 1231-1236 ◽  
Author(s):  
B L Lee ◽  
S Safrin ◽  
V Makrides ◽  
J G Gambertoglio
Keyword(s):  
Human Immunodeficiency Virus ◽  
Pneumocystis Carinii ◽  
Pharmacokinetic Interaction ◽  
Urinary Recovery ◽  
Time Curve ◽  
Concentration Time ◽  
Pharmacokinetic Interactions ◽  
Immunodeficiency Virus ◽  
Blood And Urine Samples ◽  
The Mean

Zidovudine is widely prescribed for the treatment of human immunodeficiency virus (HIV) infection. Trimethoprim and dapsone are commonly used in the management of Pneumocystis carinii pneumonia in HIV-infected patients. To examine the pharmacokinetic interactions among these drugs, eight HIV-infected patients (26 to 43 years old) with a mean CD4 count of 524.4 +/- 405.7 cells per mm3 received zidovudine (200 mg), trimethoprim (200 mg), and dapsone (100 mg) as single agents and in two- and three-drug combinations. Blood and urine samples were collected at a specified time and analyzed for zidovudine, zidovudine-glucuronide, trimethoprim, dapsone, and monoacetyl-dapsone concentrations under single-dose and steady-state conditions. Zidovudine did not influence the pharmacokinetic disposition of dapsone or trimethoprim. Dapsone had no effect on the pharmacokinetic disposition of zidovudine. Trimethoprim significantly decreased the renal clearance of zidovudine by 58% (5.0 +/- 1.8 versus 2.1 +/- 0.5 ml/min/kg of body weight [P < 0.05]). There was a concurrent 54% decrease in the mean urinary recovery of zidovudine (11.7 +/- 3.5 versus 5.4 +/- 3.0 [P < 0.05]), and the metabolic ratio was decreased by 78% (0.32 +/- 0.4 versus 0.07 +/- 0.05 [P < 0.05]). The mean area under the concentration-time curve from 0 to 6 h of the zidovudine-glucuronide/ zidovudine ratio was unchanged. We conclude that zidovudine, trimethoprim, and dapsone can be coadministered to patients with AIDS without significant pharmacokinetic interaction. However, in AIDS patients with liver impairment and impaired glucuronidation, doses of zidovudine may need to be decreased.

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