scholarly journals Pharmacokinetics of Indinavir Combined with Low-Dose Ritonavir in Human Immunodeficiency Virus Type 1-Infected Children

2004 ◽  
Vol 48 (5) ◽  
pp. 1904-1907 ◽  
Author(s):  
A. S. Bergshoeff ◽  
P. L. A. Fraaij ◽  
A. M. C. van Rossum ◽  
G. Verweel ◽  
L. H. Wynne ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Low Dose ◽  
Geometric Mean ◽  
Time Curve ◽  
Minimum Concentration ◽  
Concentration Time ◽  
Immunodeficiency Virus

ABSTRACT So far, no pediatric doses for indinavir combined with ritonavir have been defined. This study evaluated the pharmacokinetics of 400 mg of indinavir/m2 combined with 125 mg of ritonavir/m2 every 12 h (q12h) in 14 human immunodeficiency virus type 1-infected children. The area under the concentration-time curve from 0 to 24 h and the minimum concentration of drug in serum for indinavir were similar to those for 800 mg of indinavir-100 mg of ritonavir q12h in adults, while the maximum concentration of drug in serum was slightly decreased, with geometric mean ratios (90% confidence intervals in parentheses) of 1.1 (0.87 to 1.3), 0.96 (0.60 to 1.5), and 0.80 (0.68 to 0.94), respectively.

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 Pharmacokinetics of the Protease Inhibitor Indinavir in Human Immunodeficiency Virus Type 1-Infected Children

2001 ◽  
Vol 45 (3) ◽  
pp. 701-705 ◽  
Author(s):  
David M. Burger ◽  
Annemarie M. C. van Rossum ◽  
Patricia W. H. Hugen ◽  
Marja H. Suur ◽  
Nico G. Hartwig ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Drug Exposure ◽  
Optimal Dose ◽  
Dose Increase ◽  
Time Curve ◽  
Concentration Time ◽  
Immunodeficiency Virus

ABSTRACT The objective of this study was to evaluate the pharmacokinetics of indinavir in human immunodeficiency virus-infected children as part of a prospective, open, uncontrolled, multicenter study in The Netherlands. Human immunodeficiency virus type 1-infected children were monitored over 6 months of treatment with zidovudine (120 mg/m2 every 8 h [q8h]), lamivudine (4 mg/kg of body weight q12h), and indinavir (33mg/kg of metabolic weight [MW] q8h). Four weeks after the start of treatment, the steady-state pharmacokinetics of indinavir were determined by high-pressure liquid chromatography. If patients had an indinavir area under the concentration-time curve (AUC) of below 10 or above 30 mg/liter · h, a dose increase or a dose reduction was made and pharmacokinetic measurements were repeated 4 weeks later. Nineteen patients started with the dose of 33 mg/kg of MW q8h. The median AUC (range) was 10.5 (2.8 to 51.0) mg/liter · h. The median AUC (range) in 17 children treated with 50 mg/kg of MW q8h was 20.6 (4.1 to 38.7) mg/liter · h. Finally, five patients had a dose increase to 67 mg/kg of MW q8h, resulting in a median AUC (range) of 36.6 (27.2 to 80.0) mg/liter · h. After 6 months of treatment, there were 11 children with an AUC of below 20 mg/liter · h, of whom 5 (45%) had a detectable viral load, while this was the case in none of the 11 children with an AUC of higher than 20 mg/liter · h. We conclude that the optimal dose of indinavir in children to obtain drug exposure similar to that observed in adult patients is 50 mg/kg of MW q8h, which approximates 600 mg/m2 q8h. It would even be better to adjust the indinavir dose based on an AUC of greater than 20 mg/liter · h.

Low-Dose Zidovudine in Children With an Human Immunodeficiency Virus Type 1 Infection Acquired in the Perinatal Period

PEDIATRICS ◽  
1991 ◽  
Vol 88 (2) ◽  
pp. 364-370
Author(s):  
Stephane Blanche ◽  
Anne-Marie Duliege ◽  
Marianne Debré ◽  
Claude Griscelli ◽  
Maria Soledad Navarette ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Low Dose ◽  
Initial Therapy ◽  
Full Dose ◽  
Dose Therapy ◽  
Immunodeficiency Virus ◽  
The Mean

This report describes the one-year results of a noncomparative study designed to assess the safety and tolerance of low-dose zidovudine (azidothymidine) given orally to 60 human immunodeficiency virus type 1-infected infants and children. At baseline, the mean age was 1.9 years (±1.4), and all were symptomatic: 43% were P2A and 57% were P2B to F according to the Centers for Disease Control classification. All the patients received zidovudine for at least 6 months, and 52 of them (87%) completed a full year of therapy. The mean duration of follow-up was 346 days (±42) (range, 183 to 366 days). The initial therapy consisted of four daily doses of 100 mg/m2 (400 mg/m2 per day, equivalent to 20 mg/kg per day). However, this treatment was modified when neutropenia or anemia was observed. Twenty-nine children (48%) remained at the initial therapy for the entire study. Zidovudine dosage was adjusted 92 times in the other 31 children (52%), mostly due to neutropenia (83%). Altogether, the time under full-dose therapy represented 81% of the total duration of the protocol for all patients. Children with mild symptoms, P2A at study entry, were more likely to remain under full-dose therapy than children with severe symptoms, P2B to F: the time under full-dose therapy represented 91% of the duration of the protocol for the former group and only 74% for the latter one (P < .02). No clinical adverse experiences were attributed directly to zidovudine. Thirty-seven children were prescribed trimethoprim-sulfametoxazole as a prophylaxis for Pneumocystis carinii pneumonia. In a multivariate analysis, this comedication had no influence on the hematologic tolerance of zidovudine.

scholarly journals Safety and Immunogenicity of Two Influenza Virus Subunit Vaccines, with or without MF59 Adjuvant, Administered to Human Immunodeficiency Virus Type 1-Seropositive and -Seronegative Adults

2007 ◽  
Vol 15 (2) ◽  
pp. 253-259 ◽  
Author(s):  
P. Durando ◽  
D. Fenoglio ◽  
A. Boschini ◽  
F. Ansaldi ◽  
G. Icardi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Influenza Virus ◽  
Antibody Response ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Geometric Mean ◽  
Subunit Vaccines ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The objective of this study was to evaluate and compare both the safety and tolerability and the humoral and cell-mediated immune responses for two influenza virus subunit vaccines, one with MF59 adjuvant (Fluad) and one without an adjuvant (Agrippal), in healthy and in human immunodeficiency virus type 1 (HIV-1)-infected adult individuals. To achieve this aim, an open, randomized, comparative clinical trial was performed during the 2005-2006 season. A total of 256 subjects were enrolled to receive one dose of vaccine intramuscularly. Blood samples were taken at the time of vaccination and at 1 and 3 months postvaccination. A good humoral antibody response was detected for both vaccines, meeting all the criteria of the Committee for Medical Products for Human Use. After Beyer's correction for prevaccination status, Fluad exhibited better immunogenicity than Agrippal, as shown from the analysis of the geometric mean titers, with significant differences for some virus strains; however, no definitive conclusions on the clinical significance of such results can be drawn, because the method used to estimate antibody response is currently nonstandard for influenza virus vaccines. Significant induction of an antigen-specific CD4+ T-lymphocyte proliferative response was detected at all time points after immunization, for both the vaccines, among HIV-1-seronegative subjects. This was different from what was observed for HIV-1-infected individuals. In this group, significance was not reached at 30 days postvaccination (T30) for those immunized with Agrippal. Also when data were compared between treatment groups, a clear difference in the response at T30 was observed in favor of Fluad (P = 0.0002). The safety profiles of both vaccines were excellent. For HIV-1-infected individuals, no significant changes either in viremia or in the CD4+ cell count were observed at any time point. The results showed good safety and immunogenicity for both vaccines under study for both uninfected and HIV-1-infected adults, confirming current recommendations for immunization of this high-risk category.

scholarly journals Coadministration of Indinavir and Nelfinavir in Human Immunodeficiency Virus Type 1-Infected Adults: Safety, Pharmacokinetics, and Antiretroviral Activity

2002 ◽  
Vol 46 (12) ◽  
pp. 3877-3882 ◽  
Author(s):  
Sharon A. Riddler ◽  
Diane Havlir ◽  
Kathleen E. Squires ◽  
Brad Kerr ◽  
Ronald H. Lewis ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Geometric Mean ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Data ◽  
Virologic Suppression ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Combinations of protease inhibitors (PIs) can have potentially beneficial pharmacokinetic interactions, resulting in higher drug levels and less frequent dose administration. Indinavir (IDV) and nelfinavir (NFV) are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) protease and are commonly prescribed antiretroviral agents. Pilot pharmacokinetic data suggested a bidirectional enhancing interaction between IDV and NFV. A phase II study was conducted to evaluate the safety, pharmacokinetics, and antiviral activity of IDV plus NFV given in a combination every 12 h in HIV-1-infected subjects. IDV plus NFV was given as a twice-daily regimen to 20 HIV-1-infected subjects who were PI naive (11 of 20 were antiretroviral naive). After week 18, nucleoside reverse transcriptase inhibitors were added to the treatment regimen in seven subjects. The enrolled subjects had a geometric mean baseline plasma HIV-1 RNA of 63,095 copies/ml and a mean CD4+ cell count of 266 cells/mm3. Pharmacokinetic evaluations were performed at the following doses: IDV at 1,000 mg every 12 h (q12h) plus NFV at 750 mg q12h, IDV at 1,000 mg q12h plus NFV at 1,000 mg q12h, and IDV at 1,200 mg q12h plus NFV at 1,250 mg q12h. The coadministration of IDV plus NFV resulted in a modest inhibition of IDV elimination, resulting in a plasma profile of IDV 1200 mg q12h (with NFV at 1,250 mg q12h) that was comparable to the standard IDV dose of 800 mg q8h. In contrast, IDV had no apparent effect on the pharmacokinetic profile of NFV. The combination of IDV and NFV was generally well tolerated and resulted in sustained virologic suppression with 45% of the subjects having an HIV-1 RNA level in plasma of <400 copies/ml at week 72 (intent-to-treat).

scholarly journals Didanosine reduces atevirdine absorption in subjects with human immunodeficiency virus infections.

1996 ◽  
Vol 40 (3) ◽  
pp. 767-771 ◽  
Author(s):  
G D Morse ◽  
M A Fischl ◽  
M J Shelton ◽  
M T Borin ◽  
M R Driver ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Maximum Concentration ◽  
Concurrent Administration ◽  
Time Curve ◽  
Concentration Time ◽  
Immunodeficiency Virus ◽  
Combination Regimens

Atevirdine is a nonnucleoside reverse transcriptase inhibitor with in vitro activity against human immunodeficiency virus type 1 and is currently in phase II clinical trials. Atevirdine is most soluble at a pH of < 2, and therefore, normal gastric acidity is most likely necessary for optimal bioavailability. Because of the rapid development of resistance in vitro, atevirdine is being evaluated in combination with didanosine and/or zidovudine in both two- and three-drug combination regimens. To examine the influence of concurrent didanosine (buffered tablet formulation) on the disposition of atevirdine, 12 human immunodeficiency virus type 1-infected subjects (mean CD4+ cell count, 199 cells per mm3; range, 13 to 447 cells/mm3) participated in a three-way, partially randomized, crossover, single-dose study to evaluate the pharmacokinetics of didanosine and atevirdine when each drug was given alone (treatments A and B, respectively) versus concurrently (treatment C). Concurrent administration of didanosine and atevirdine significantly reduced the maximum concentration of atevirdine in serum from 3.45 +/- 2.8 to 0.854 +/- 0.33 microM (P = 0.004). Likewise, the mean atevirdine area under the concentration-time curve from 0 to 24 h after administration of the combination was reduced to 6.47 +/- 2.2 microM.h (P = 0.004) relative to a value of 11.3 +/- 4.8 microM.h for atevirdine alone. Atevirdine had no statistically significant effect on the pharmacokinetic parameters of didanosine. Concurrent administration of single doses of atevirdine and didanosine resulted in a markedly lower maximum concentration of atevirdine in serum and area under the concentration-time curve, with a minimal effect on the disposition of didanosine. It is unknown whether an interaction of similar magnitude would occur under steady-state conditions; thus, combination regimens which include both atevirdine and didanosine should be designed so that their administration times are separated. Since the duration of the buffering effect of didanosine formulations is unknown, atevirdine should be given prior to didanosine.

scholarly journals Maraviroc (UK-427,857), a Potent, Orally Bioavailable, and Selective Small-Molecule Inhibitor of Chemokine Receptor CCR5 with Broad-Spectrum Anti-Human Immunodeficiency Virus Type 1 Activity

2005 ◽  
Vol 49 (11) ◽  
pp. 4721-4732 ◽  
Author(s):  
Patrick Dorr ◽  
Mike Westby ◽  
Susan Dobbs ◽  
Paul Griffin ◽  
Becky Irvine ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Inhibitory Concentration ◽  
Geometric Mean ◽  
In Vivo Models ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Maraviroc (UK-427,857) is a selective CCR5 antagonist with potent anti-human immunodeficiency virus type 1 (HIV-1) activity and favorable pharmacological properties. Maraviroc is the product of a medicinal chemistry effort initiated following identification of an imidazopyridine CCR5 ligand from a high-throughput screen of the Pfizer compound file. Maraviroc demonstrated potent antiviral activity against all CCR5-tropic HIV-1 viruses tested, including 43 primary isolates from various clades and diverse geographic origin (geometric mean 90% inhibitory concentration of 2.0 nM). Maraviroc was active against 200 clinically derived HIV-1 envelope-recombinant pseudoviruses, 100 of which were derived from viruses resistant to existing drug classes. There was little difference in the sensitivity of the 200 viruses to maraviroc, as illustrated by the biological cutoff in this assay (= geometric mean plus two standard deviations [SD] of 1.7-fold). The mechanism of action of maraviroc was established using cell-based assays, where it blocked binding of viral envelope, gp120, to CCR5 to prevent the membrane fusion events necessary for viral entry. Maraviroc did not affect CCR5 cell surface levels or associated intracellular signaling, confirming it as a functional antagonist of CCR5. Maraviroc has no detectable in vitro cytotoxicity and is highly selective for CCR5, as confirmed against a wide range of receptors and enzymes, including the hERG ion channel (50% inhibitory concentration, >10 μM), indicating potential for an excellent clinical safety profile. Studies in preclinical in vitro and in vivo models predicted maraviroc to have human pharmacokinetics consistent with once- or twice-daily dosing following oral administration. Clinical trials are ongoing to further investigate the potential of using maraviroc for the treatment of HIV-1 infection and AIDS.

scholarly journals A Randomized Trial of High‐ versus Low‐Dose Subcutaneous Interleukin‐2 Outpatient Therapy for Early Human Immunodeficiency Virus Type 1 Infection

1999 ◽  
Vol 179 (4) ◽  
pp. 849-858 ◽  
Author(s):  
Richard T. Davey, Jr. ◽  
Doreen G. Chaitt ◽  
Jeffrey M. Albert ◽  
Stephen C. Piscitelli ◽  
Joseph A. Kovacs ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Randomized Trial ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Low Dose ◽  
Interleukin 2 ◽  
Outpatient Therapy ◽  
Immunodeficiency Virus ◽  
Early Human

scholarly journals Clinical Response and Tolerability to and Safety of Saquinavir with Low-Dose Ritonavir in Human Immunodeficiency Virus Type 1-Infected Mothers and Their Infants

2007 ◽  
Vol 51 (6) ◽  
pp. 2208-2210 ◽  
Author(s):  
Carmen D. Zorrilla ◽  
Russell Van Dyke ◽  
Arlene Bardeguez ◽  
Edward P. Acosta ◽  
Betsy Smith ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Adverse Events ◽  
Pregnant Women ◽  
Clinical Response ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Low Dose ◽  
Immunodeficiency Virus ◽  
Liver Transaminases

ABSTRACT Saquinavir boosted with low-dose ritonavir given with zidovudine and lamivudine was well tolerated by pregnant women and their infants. All mothers had <400 human immunodeficiency virus type 1 RNA copies/ml at delivery. Two had elevated liver transaminases and amylase. Seven infant adverse events were possibly treatment related (anemia, neutropenia, and hyperbilirubinemia).

Sign in / Sign up

Export Citation Format

Share Document