scholarly journals Indinavir Pharmacokinetics and Parmacodynamics in Children with Human Immunodeficiency Virus Infection

2000 ◽  
Vol 44 (3) ◽  
pp. 752-755 ◽  
Author(s):  
Giorgio Gatti ◽  
Alessandra Vigano' ◽  
Natascia Sala ◽  
Stefano Vella ◽  
Matteo Bassetti ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dosage Regimen ◽  
Renal Toxicity ◽  
Significant Negative Correlation ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Time Curve ◽  
Number Of Patients ◽  
Immunodeficiency Virus ◽  
The Difference

ABSTRACT The indinavir dosage regimen currently used for human immunodeficiency virus (HIV)-infected children is not based on pharmacokinetic data obtained in the target patient population. The purpose of our study was to characterize indinavir pharmacokinetics and pharmacodynamics in HIV-infected children. Eleven children (age range, 9.0 to 13.6 years; weight range, 21.7 to 56.0 kg) receiving indinavir (500 mg/m2 every 8 h) in combination with lamivudine and stavudine were studied. The correlation of indinavir pharmacokinetic parameters and demographic parameters was evaluated. Also, the pharmacodynamic relationship between parameters of indinavir exposure and parameters of renal toxicity and immunologic recovery was studied. The area under the indinavir concentration-time curve (AUC) and patient body surface area (BSA) showed a significant negative correlation (r = 0.73; P = 0.012). Patients with smaller BSA had excessive indinavir AUC compared to adults. On the other hand, the median minimum drug concentration in plasma (C min) was lower than that reported for adults. The maximum indinavir concentration in serum was higher in patients with renal toxicity (5 out of 11 children), but the difference was not statistically significant (15.3 ± 8.2 versus 9.8 ± 4.4 mg/liter; P = 0.19). There was a trend toward higher immunologic efficacy in patients with greater indinavir exposure: the time-averaged AUC of the percentage of CD4+ lymphocytes over the baseline value for patients with indinavir C min > 95% inhibitory concentration (IC95) was higher than in patients withC min < IC95(P = 0.068). Our study suggests that a dose reduction may be appropriate for children with small BSA and that a 6-h dosage regimen may be indicated for a substantial percentage of patients. Due to the low number of patients enrolled in this study, our results should be confirmed by a larger study.

scholarly journals Effects of Valproic Acid Coadministration on Plasma Efavirenz and Lopinavir Concentrations in Human Immunodeficiency Virus-Infected Adults

2004 ◽  
Vol 48 (11) ◽  
pp. 4328-4331 ◽  
Author(s):  
Robert DiCenzo ◽  
Derick Peterson ◽  
Kim Cruttenden ◽  
Gene Morse ◽  
Garret Riggs ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Valproic Acid ◽  
Geometric Mean ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Blood Samples ◽  
Immunodeficiency Virus ◽  
Before And After ◽  
Trough Concentrations ◽  
Hiv 1

ABSTRACT Valproic acid (VPA) has the potential to benefit patients suffering from human immunodeficiency virus (HIV)-associated cognitive impairment. The purpose of this study was to determine if VPA affects the plasma concentration of efavirenz (EFV) or lopinavir. HIV type 1 (HIV-1)-infected patients receiving EFV or lopinavir-ritonavir (LPV/r) had 9 or 10 blood samples drawn over 8 to 24 h of a dosing interval at steady state before and after receiving 250 mg of VPA twice daily for 7 days. VPA blood samples drawn before (C 0) and 8 h after the morning dose (8 h) were compared to blood samples from a group of HIV-1-infected subjects who were taking either combined nucleoside reverse transcriptase inhibitors alone or had discontinued antiretroviral therapy. Pharmacokinetic parameters were calculated by noncompartmental analysis, and tests of bioequivalence were based on 90% confidence intervals (CIs) for ratios or differences. The geometric mean ratio (GMR) (90% CI) of the areas under the concentration-time curve from 0 to 24 h (AUC0-24s) of EFV (n = 11) with and without VPA was 1.00 (0.85, 1.17). The GMR (90% CI) of the AUC0-8s of LPV (n = 8) with and without VPA was 1.38 (0.98, 1.94). The differences (90% CI) in mean C 0 and 8-h VPA concentrations versus the control (n = 11) were −1.0 (−9.4, 7.4) μg/ml and −2.1 (−11.1, 6.9) μg/ml for EFV (n = 10) and −5.0 (−13.2, 3.3) μg/ml and −6.7 (−17.6, 4.2) μg/ml for LPV/r (n = 11), respectively. EFV administration alone is bioequivalent to EFV and VPA coadministration. LPV concentrations tended to be higher when the drug was combined with VPA. Results of VPA comparisons fail to raise concern that coadministration with EFV or LPV/r will significantly influence trough concentrations of VPA.

scholarly journals Steady-State Pharmacokinetics of Abacavir in Plasma and Intracellular Carbovir Triphosphate following Administration of Abacavir at 600 Milligrams Once Daily and 300 Milligrams Twice Daily in Human Immunodeficiency Virus-Infected Subjects

2009 ◽  
Vol 53 (4) ◽  
pp. 1532-1538 ◽  
Author(s):  
Graeme Moyle ◽  
Marta Boffito ◽  
Carl Fletcher ◽  
Chris Higgs ◽  
Phillip E. Hay ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
High Performance ◽  
Pharmacokinetic Parameters ◽  
Virologic Suppression ◽  
Open Label ◽  
Time Curve ◽  
Mixed Effect ◽  
Once Daily ◽  
Immunodeficiency Virus ◽  
And Gender

ABSTRACT Abacavir (ABC) is administered either at 600 mg once daily (ABC 600 mg QD) or 300 mg twice daily (ABC 300 mg BID) in anti-human immunodeficiency virus (anti-HIV) combination therapy. Although ABC plasma pharmacokinetics following each regimen has been well defined, no study has directly compared the regimens with respect to pharmacokinetics of ABC's active intracellular anabolite, carbovir-triphosphate (CBV-TP). In an open-label, two-period, crossover study, 34 HIV-infected male and female subjects stabilized on antiretroviral regimens containing either ABC 600 mg QD or ABC 300 mg BID received their usual doses on days −1 and 1 and then switched regimens for days 2 to 11. Serial blood samples collected on days 1 and 11 were assayed for plasma ABC and intracellular CBV-TP concentrations using validated high-performance liquid chromatography-tandem mass spectrometry methods. Pharmacokinetic parameters were calculated using noncompartmental methods. Analysis of variance with a mixed-effect model was performed for treatment and gender comparisons. In 27 evaluable subjects, the regimens provided bioequivalent ABC daily areas under the concentration-time curve from 0 to 24 h (AUC0-24) and comparable CBV-TP concentrations at the end of the dosing interval (C τ). As expected, ABC QD resulted in 109% higher ABC maximum concentrations of drug in plasma (C max) than did ABC BID. ABC QD also resulted in 32% higher CBV-TP AUC0-24 and 99% higher CBV-TP C max than did ABC BID. Females had a 38% higher weight-adjusted ABC AUC0-24 and 81% higher weight-adjusted CBV-TP AUC0-24 than did males. Virologic suppression was maintained during regimen switch, and no tolerability differences between regimens were observed. In conclusion, this study showed that ABC 600 mg QD and ABC 300 mg BID regimens led to similar intracellular CBV-TP C τ values, thus providing pharmacokinetic support for the interchangeability of these two regimens. Women had higher intracellular CBV-TP exposure than did men.

scholarly journals Clinical and Pharmacokinetic Data Support Once-Daily Low-Dose Boosted Saquinavir (1,200 Milligrams Saquinavir with 100 Milligrams Ritonavir) in Treatment-Naive or Limited Protease Inhibitor-Experienced Human Immunodeficiency Virus-Infected Patients

2007 ◽  
Vol 51 (6) ◽  
pp. 2035-2042 ◽  
Author(s):  
Ana Marin-Niebla ◽  
Luis Fernando Lopez-Cortes ◽  
Rosa Ruiz-Valderas ◽  
Pompeyo Viciana ◽  
Rosario Mata ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitor ◽  
Virological Failure ◽  
Low Dose ◽  
Pharmacokinetic Data ◽  
Time Curve ◽  
Once Daily ◽  
Intention To Treat ◽  
Immunodeficiency Virus ◽  
Treatment Naïve

ABSTRACT We evaluated the plasma and intracellular pharmacokinetics, clinical efficacy, and safety of once-daily low-dose boosted saquinavir (SQVr; 1,200 of saquinavir [SQV] with 100 mg of ritonavir) plus two nucleotide reverse transcriptase inhibitors in treatment-naive or limited protease inhibitor (PI)-experienced human immunodeficiency virus (HIV)-infected patients. A prospective study without entry restrictions on the plasma HIV-RNA (VL) or CD4 cell count was carried out. Plasma and intracellular SQV levels were measured by high-performance liquid chromatography. Efficacy was evaluated by an intention-to-treat analysis; treatment failure was defined as virological failure (a VL of >50 copies/ml after 24 weeks or a confirmed rebound to >50 copies/ml) or interruption for any reason. A total of 151 patients were included in the study (106 of them either had never received PI or had no previous virological failure on PIs) and could be characterized as follows: previous C3 stage, 28.9%; injection-drug users, 69.1%; subjects with chronic viral hepatitis, 53%; and subjects with cirrhosis, 10%. The median baseline CD4 level was 184/μl, and the median VL was 4.8 log10 copies/ml. Median C max, area under the concentration-time curve from 0 to 24 h, and C min plasma and intracellular SQV levels were 3,672 and 10,105 ng/ml, 34,283 and 99,535 ng·h/ml, and 359 and 1,062 ng/ml, respectively. The efficacy as determined by intention to treat at 52 weeks was 69.7% (96% in the on-treatment analysis), with similar results regardless of the baseline VL and CD4 counts. Only five patients had virological failure despite adequate C min levels, but with a poor adherence (the only variable related to virological failure). Adverse events caused the withdrawal of the treatment in four patients (2.6%). In conclusion, given the pharmacokinetic profile, efficacy, and tolerability of this regimen, once-daily low-dose SQVr may be considered a treatment option in treatment-naive or limited PI-experienced HIV-infected patients, with the additional benefit of being currently the least-expensive PI-based regimen available.

scholarly journals Pharmacokinetics of Ritonavir and Delavirdine in Human Immunodeficiency Virus-Infected Patients

2003 ◽  
Vol 47 (5) ◽  
pp. 1694-1699 ◽  
Author(s):  
Mark J. Shelton ◽  
Ross G. Hewitt ◽  
John Adams ◽  
Andrew Della-Coletta ◽  
Steven Cox ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Systemic Exposure ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Minimum Concentration ◽  
Mean Values ◽  
Immunodeficiency Virus ◽  
The Mean ◽  
Full Dosage ◽  
Delavirdine Mesylate

ABSTRACT To evaluate the pharmacokinetic effect of adding delavirdine mesylate to the antiretroviral regimens of human immunodeficiency virus (HIV)-infected patients stabilized on a full dosage of ritonavir (600 mg every 12 h), 12 HIV-1-infected subjects had delavirdine mesylate (400 mg every 8 h) added to their current antiretroviral regimens for 21 days. Ritonavir pharmacokinetics were evaluated before (day 7) and after (day 28) the addition of delavirdine, and delavirdine pharmacokinetics were evaluated on day 28. The mean values (± standard deviations) for the maximum concentration in serum (C max) of ritonavir, the area under the concentration-time curve from 0 to 12 h (AUC0-12), and the minimum concentration in serum (C min) of ritonavir before the addition of delavirdine were 14.8 ± 6.7 μM, 94 ± 36 μM · h, and 3.6 ± 2.1 μM, respectively. These same parameters were increased to 24.6 ± 13.9 μM, 154 ± 83 μM · h, and 6.52 ± 4.85 μM, respectively, after the addition of delavirdine (P is <0.05 for all comparisons). Delavirdine pharmacokinetic parameters in the presence of ritonavir included a C max of 23 ± 16 μM, an AUC0-8 of 114 ± 75 μM · h, and a C min of 9.1 ± 7.5 μM. Therefore, delavirdine increases systemic exposure to ritonavir by 50 to 80% when the drugs are coadministered.

scholarly journals Pyrimethamine pharmacokinetics in human immunodeficiency virus-positive patients seropositive for Toxoplasma gondii.

1996 ◽  
Vol 40 (6) ◽  
pp. 1360-1365 ◽  
Author(s):  
J M Jacobson ◽  
M Davidian ◽  
P M Rainey ◽  
R Hafner ◽  
R H Raasch ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Toxoplasma Gondii ◽  
Drug Users ◽  
Compartment Model ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Immunodeficiency Virus

Pyrimethamine pharmacokinetics were studied in 11 human immunodeficiency virus (HIV)-positive patients who were seropositive for exposure to Toxoplasma gondii and were taking zidovudine (AIDS Clinical Trials Group Protocol 102). Pyrimethamine was administered at 50 mg daily for 3 weeks to achieve steady state, and pharmacokinetic profiles were determined after administration of the last dose. Noncompartmental and compartmental analyses were performed. Population pharmacokinetic analysis assuming a one-compartment model yielded the following estimates: area under the 24-h concentration-time curve, 42.7 +/- 12.3 micrograms.h/ml; halflife, 139 +/- 34 h; clearance, 1.28 +/- 0.41 liters/h; volume of distribution, 246 +/- 641; and absorption rate constant, 1.5 +/- 1.3 liters/h. These values are similar to those seen in subjects without HIV infection. Pyrimethamine pharmacokinetics did not differ significantly in those subjects who were intravenous drug users. Adverse effects were noted in 73% of those initially enrolled in this study, leading to discontinuation for 38%. No association was noted between pyrimethamine levels and the incidence of adverse events. No significant differences were seen in zidovudine pharmacokinetic parameters obtained from studies performed before and during treatment with pyrimethamine. In summary, pyrimethamine exhibited pharmacokinetics in HIV-infected patients that were similar to those in non-HIV-infected subjects and it did not alter the pharmacokinetics of zidovudine in these patients.

scholarly journals Pharmacokinetic and Pharmacodynamic Study of the Human Immunodeficiency Virus Protease Inhibitor Amprenavir after Multiple Oral Dosing

2001 ◽  
Vol 45 (1) ◽  
pp. 30-37 ◽  
Author(s):  
Brian M. Sadler ◽  
Catherine Gillotin ◽  
Yu Lou ◽  
Daniel S. Stein
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Dose Range ◽  
Area Under The Curve ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Protease Enzyme ◽  
Immunodeficiency Virus

ABSTRACT In a dose-ranging study of amprenavir (formerly 141W94), an inhibitor of the protease enzyme of human immunodeficiency virus (HIV) type 1, single-dose and steady-state pharmacokinetic parameters were estimated from plasma samples collected on day 1 and during week 3, respectively. Amprenavir was administered on either a twice-daily (b.i.d.) or three-times-daily dosage schedule to 62 HIV-infected adults, 59 of whom had pharmacokinetic data. Log-log regression analysis (the power model) revealed that the steady-state area under the curve (AUCss) and the maximum, minimum, and average concentrations at steady state (C max,ss,C min,ss, and C avg,ss, respectively) increased in a dose-proportional manner over the 300- to 1,200-mg dose range. Steady-state clearance was dose independent. AUCss/AUC0→∞ decreased linearly with dose and correlated significantly with treatment-associated decreases in α1-acid glycoprotein. After 3 weeks, the dose of 1,200 mg b.i.d. provided a median amprenavir Cmin,ss (0.280 μg/ml) that was higher than the median in vitro 50% inhibitory concentration for clinical HIV isolates (0.023 μg/ml), even after adjustment for protein binding. The median amprenavir C min,sswas also greater than the estimated in vivo trough concentration calculated to yield 90% of the maximum antiviral effect (0.228 μg/ml) over 4 weeks. A pharmacodynamic analysis of the relationship between steady-state pharmacokinetic parameters and safety revealed headache and oral numbness to be the only side effects significantly associated with C max. The pharmacodynamic relationship defined in this study supports the use of 1,200 mg b.i.d. as the approved dose of amprenavir.

scholarly journals Steady-State Pharmacokinetics of a Double-Boosting Regimen of Saquinavir Soft Gel plus Lopinavir plus Minidose Ritonavir in Human Immunodeficiency Virus-Infected Adults

2004 ◽  
Vol 48 (11) ◽  
pp. 4256-4262 ◽  
Author(s):  
Esteban Ribera ◽  
Rosa M. Lopez ◽  
Marjorie Diaz ◽  
Leonor Pou ◽  
Lidia Ruiz ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Rescue Therapy ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Minimum Concentration ◽  
Immunodeficiency Virus ◽  
Strong Linear Correlation ◽  
Drug Doses ◽  
Therapeutic Doses

ABSTRACT Management of treatment-experienced human immunodeficiency virus patients has become complex, and therapy may need to include two protease inhibitors at therapeutic doses. The objective of this study was to characterize the pharmacokinetics in serum of saquinavir (1,000 mg twice daily [b.i.d.]), lopinavir (400 mg b.i.d.), and ritonavir (100 mg b.i.d.) in a multidrug rescue therapy study and to investigate whether steady-state pharmacokinetics of lopinavir-ritonavir are affected by coadministration of saquinavir. Forty patients were included (25 given ritonavir, lopinavir, and saquinavir and 15 given ritonavir and lopinavir). The median pharmacokinetic parameters of lopinavir were as follows: area under the concentration-time curve from 0 to 12 h (AUC0-12), 85.1 μg/ml · h; maximum concentration of drug in serum (C max), 10.0 μg/ml; trough concentration of drug in serum (C trough), 7.3 μg/ml; and minimum concentration of drug in serum (C min), 5.5 μg/ml. Lopinavir concentrations were similar in patients with and without saquinavir. The median pharmacokinetic parameters for saquinavir were as follows: AUC0-12, 22.9 μg/ml · h; C max, 2.9 μg/ml; C trough, 1.6 μg/ml; and C min, 1.4 μg/ml. There was a strong linear correlation between lopinavir and ritonavir and between saquinavir and ritonavir concentrations in plasma. The correlation between lopinavir and saquinavir levels was weaker. We found higher saquinavir concentrations in women than in men, with no difference in lopinavir levels. Only patients with very high body weight presented lopinavir and saquinavir concentrations lower than the overall group. Ritonavir has a double-boosting function for both lopinavir and saquinavir, and in terms of pharmacokinetics, the drug doses selected seemed appropriate for combining these agents in a dual protease inhibitor-based antiretroviral regimen for patients with several prior virologic failures.

scholarly journals Pilot Pharmacokinetic Study of Human Immunodeficiency Virus-Infected Patients Receiving Tenofovir Disoproxil Fumarate (TDF): Investigation of Systemic and Intracellular Interactions between TDF and Abacavir, Lamivudine, or Lopinavir-Ritonavir

2009 ◽  
Vol 53 (5) ◽  
pp. 1937-1943 ◽  
Author(s):  
Alain Pruvost ◽  
Eugènia Negredo ◽  
Frédéric Théodoro ◽  
Jordi Puig ◽  
Mikaël Levi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Pharmacokinetic Parameters ◽  
Reverse Transcriptase Inhibitors ◽  
Plasma Exposure ◽  
Time Curve ◽  
Residual Concentration ◽  
Concentration Time ◽  
Immunodeficiency Virus ◽  
Liquid Chromatography Tandem Mass

ABSTRACT Previous work has demonstrated the existence of systemic interaction between tenofovir (TFV) disoproxil fumarate (TDF) and didanosine as well as between TDF and lopinavir-ritonavir (LPV/r). Here we investigated TDF interactions with the nucleoside reverse transcriptase inhibitors (NRTIs) lamivudine (3TC) and abacavir (ABC), comparing both the concentrations of nucleoside/nucleotide reverse transcriptase inhibitors in plasma and the intracellular concentrations of their triphosphate metabolites (NRTI-TP) for human immunodeficiency virus-infected patients receiving these NRTIs with TDF and after 4 weeks of TDF interruption. We also looked at interactions between TDF-ABC and LPV/r, comparing patients receiving or not receiving LPV/r. Blood samples were taken at baseline and at 1, 2, and 4 h after dosing. Liquid chromatography-tandem mass spectrometry was used to measure NRTIs and NRTI-TPs. Statistical analyses were performed on pharmacokinetic parameters: the area under the concentration-time curve from 0 to 4 h (AUC0-4), the maximum concentration of the drug (C max), and the residual concentration of the drug at the end of the dosing interval (C trough) for plasma and the AUC0-4 and C trough for intracellular data. Among the groups of patient discontinuing TDF, the very long intracellular half-life of elimination (150 h) of TFV-DP (the diphosphorylated metabolite of TFV, corresponding to a triphosphorylated species) was confirmed. Comparison between groups as well as the longitudinal study showed no significant systemic or intracellular interaction between TDF and ABC or 3TC. Significant differences were observed between patients receiving LVP/r and those receiving nevirapine. For ABC, plasma exposure was decreased (40%) under LVP/r, while, in contrast, plasma exposure to TFV was increased by 50% and the intracellular TFV-DP AUC0-4 was increased by 59%. A trend for a gender effect was observed for TFV-DP at the intracellular level, with higher and C trough values for women.

scholarly journals Multiple-Dose Pharmacokinetics and Pharmacodynamics of Abacavir Alone and in Combination with Zidovudine in Human Immunodeficiency Virus-Infected Adults

2000 ◽  
Vol 44 (8) ◽  
pp. 2061-2067 ◽  
Author(s):  
James A. McDowell ◽  
Yu Lou ◽  
William S. Symonds ◽  
Daniel S. Stein
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Multiple Dose ◽  
Total Daily Dose ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Time Curve ◽  
Immunodeficiency Virus ◽  
Multiple Dose Pharmacokinetics ◽  
Hiv 1

ABSTRACT Abacavir (1592U89) is a nucleoside reverse transcriptase inhibitor with potent activity against human immunodeficiency virus type 1 (HIV-1) when used alone or in combination with other antiretroviral agents. The present study was conducted to determine the multiple-dose pharmacokinetics and pharmacodynamics of abacavir in HIV-1-infected subjects following oral administration of daily doses that ranged from 600 to 1,800 mg, with and without zidovudine. Seventy-nine subjects received abacavir monotherapy for 4 weeks (200, 400, or 600 mg every 8 hours [TID] and 300 mg every 12 h [BID]) and thereafter received either zidovudine (200 mg TID or 300 mg BID) or matching placebo with abacavir for 8 additional weeks. Pharmacokinetic parameters were calculated for abacavir after administration of the first dose and at week 4 and for abacavir, zidovudine, and its glucuronide metabolite at week 12. The concentrations of abacavir in cerebrospinal fluid were determined in a subset of subjects. Steady-state plasma abacavir concentrations were achieved by week 4 of monotherapy and persisted to week 12. At steady state, abacavir pharmacokinetic parameters (area under the plasma concentration-time curve for a dosing interval [AUCtau] and peak concentration [C max]) were generally proportional to dose over the range of a 600- to 1,200-mg total daily dose. Coadministration of zidovudine with abacavir produced a small and inconsistent effect on abacavir pharmacokinetic parameters across the different doses. At the clinical abacavir dose (300 mg BID) zidovudine coadministration had no effect on the abacavir AUCtau, which is most closely associated with efficacy. Zidovudine pharmacokinetics appeared to be unaffected by abacavir. Statistically significant but weak relationships were found for the change in the log10 HIV-1 RNA load from the baseline to week 4 versus total daily AUCtau and C tau(P < 0.05). The incidence of nausea was significantly associated with total daily AUCtau andC max. In conclusion, abacavir has predictable pharmacokinetic characteristics following the administration of multiple doses.

scholarly journals Pharmacokinetics of itraconazole (oral solution) in two groups of human immunodeficiency virus-infected adults with oral candidiasis.

1997 ◽  
Vol 41 (11) ◽  
pp. 2554-2558 ◽  
Author(s):  
J Reynes ◽  
C Bazin ◽  
F Ajana ◽  
A Datry ◽  
J P Le Moing ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Cell Count ◽  
Oral Candidiasis ◽  
Oral Solution ◽  
Cd4 T Cell ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Immunodeficiency Virus ◽  
Cd4 T Cell Count

The pharmacokinetics of itraconazole formulated in a hydroxypropyl-beta-cyclodextrin oral solution was determined for two groups of human immunodeficiency virus (HIV)-infected adults with oral candidiasis (group A, 12 patients with CD4+ T-cell count of >200/mm3 and no AIDS, and group B, 11 patients with CD4+ T-cell count of <100/mm3 and AIDS). Patients received 100 mg of itraconazole every 12 h for 14 days. Concentrations of itraconazole and hydroxyitraconazole, the main active metabolite, were measured in plasma and saliva by high-performance liquid chromatography. Pharmacokinetic parameters determined at days 1 and 14 (the area under the concentration-time curve from 0 to 10 h, the maximum concentration of drug in plasma [Cmax], and the time to Cmax) were comparable in both groups. Trough levels in plasma (Cmin) were similar in both groups for the complete duration of the study. An effective concentration of itraconazole in plasma (>250 ng/ml) was reached at day 4. At day 14, Cmin values of itraconazole were 643 +/- 304 and 592 +/- 401 ng/ml for groups A and B, respectively, and Cmin values of hydroxyitraconazole were 1,411 +/- 594 and 1,389 +/- 804 ng/ml for groups A and B, respectively. In saliva, only unchanged itraconazole was detected, and mean concentrations were still high (>250 ng/ml) 4 h after the intake, which may contribute to the fast clinical response. In conclusion, the oral solution of itraconazole generates effective levels in plasma and saliva in HIV-infected patients; its relative bioavailability is not modified by the stage of HIV infection.

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