Changes in renal function associated with indinavir

Boubaker, K; Sudre, Philippe; Bally, Frank; Vogel, G; Meuwly, Jean‐Yves; Glauser, M. P.; Telenti, Amalio

doi:10.1097/00002030-199818000-00003

Cited by 73 publications

(38 citation statements)

References 10 publications

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“…Twice-daily regimens of 800 mg of indinavir plus 100 to 200 mg of ritonavir are considered effective but poorly tolerated, and concerns about the increase in nephrotoxicity have been raised (6). A limited number of patients (n ϭ 7) were affected in our population study, and only a marginal association between C max and this side effect was observed.…”

Section: Discussionmentioning

confidence: 88%

Population Pharmacokinetics of Indinavir in Patients Infected with Human Immunodeficiency Virus

Csajka¹,

Marzolini²,

Fattinger

et al. 2004

Antimicrob Agents Chemother

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Indinavir is currently used at a fixed dose of 800 mg either three times a day or twice a day in combination with 100 mg of ritonavir. Dosage individualization based on plasma concentration monitoring might, however, be indicated. This study aimed to assess the pharmacokinetic profile of indinavir in patients infected with human immunodeficiency virus to characterize interpatient and intrapatient variability and to build up a Bayesian approach for dosage adaptation. A population analysis was performed with the NONMEM computer program with 569 plasma samples from a cohort of 239 unselected patients receiving indinavir. A onecompartment model with first-order absorption was adapted, and the influences of clinical characteristics on oral clearance (CL) and distribution volume (V) were examined. Predicted average drug exposure and trough and peak concentrations were derived for each patient and correlated with efficacy and toxicity markers. The population estimates of CL were 32.4 liters/h for female and 42.0 liters/h for male patients; oral V was 65.7 liters; and the rate constant of absorption (K a ) was 1.0 h ؊1 . CL decreased by 63% with ritonavir intake and was moderately correlated to body weight. Both interpatient variability, best assigned to oral CL (coefficient of variation [CV], 39%) and K a (CV, 67%), and intrapatient variability were large (CV, 41%; standard deviation, 670 g/liter). In conclusion, initial indinavir dosage should be decided according to ritonavir intake and sex, prior to plasma concentration measurements. The high interpatient pharmacokinetic variability represents an argument for therapeutic drug monitoring.Indinavir is a protease inhibitor (PI) used in association with reverse transcriptase inhibitors in the treatment of human immunodeficiency virus type 1 (HIV-1) infection. The currently recommended adult dosage is either 800 mg t.i.d or 800 mg b.i.d in combination with low-dose ritonavir. Indinavir has unfavorable pharmacokinetic behavior, with high peak concentrations that create a risk of adverse reactions, such as nephrolithiasis (14), and minimum concentrations that are only slightly above the 95% inhibitory concentration of the virus under the t.i.d regimen, due to extensive cytochrome P450-mediated metabolism (http://www.eudra.org/humandocs/humans /epar/crixivan/crixivan.htm). Large interpatient and intrapatient variability in indinavir disposition, as reported in other population analyses (27,29), and poor adherence to recommendations regarding food intake or drug interactions may further weaken the antiviral coverage in spite of a strict compliance with the every-8-h regimen. Insufficient concentrations in plasma are clearly associated with a rebound in viral load and an increased risk of emergence of viral resistances. Combining ritonavir as a kinetic booster in indinavir-containing regimens has been successful, allowing the daily doses of such regimens to be reduced while at the same time improving their antiviral efficacy (7,10,18,28). New strategies based on target concen...

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Section: Discussionmentioning

confidence: 88%

Population Pharmacokinetics of Indinavir in Patients Infected with Human Immunodeficiency Virus

Csajka¹,

Marzolini²,

Fattinger

et al. 2004

Antimicrob Agents Chemother

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“…Prevention of indinavir crystalluria and nephrolithiasis depends on maintenance of a daily fluid intake of at least 1.5 to 2 L. Urinary acidification, although theoretically of benefit, is not generally recommended. Patients who are treated with higher doses (e.g., Ն1000 mg twice daily) over longer periods of time are more likely to develop crystalluria; other risk factors are low lean body mass, co-infection with hepatitis B or C virus, and use of acyclovir or trimethoprim-sulfamethoxazole (84,86,93). In patients who develop indinavir-related nephrolithiasis, therapy usually can be resumed after resolution of the acute episode once adequate volume status is achieved.…”

Section: Renal Toxicity Of Antiretroviral Agentsmentioning

confidence: 99%

Highly Active Antiretroviral Therapy and the Kidney

Berns

Kasbekar

2006

Clinical Journal of the American Society of Nephrology

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Highly active antiretroviral therapy has dramatically altered the treatment and life expectancy of individuals who are infected with HIV. More than 20 antiretroviral drugs and drug combinations now are available in the United States. Nephrologists need to have an understanding of the pharmacokinetics of antiretroviral medications and the proper dosing of these medications in patients with impaired kidney function. It is also important for nephrologists to be aware of drug-drug interactions that can occur between antiretroviral medications and other medications that they may prescribe, including immunosuppressive medications that are used for renal transplantation, as this becomes more common in HIV-infected patients. Adverse reactions that affect the kidneys and cause fluid-electrolyte complications occur with certain antiretroviral agents, although most are relatively free of nephrotoxicity. This article reviews the clinical pharmacology and dosing modifications of the newer antiretroviral medications in patients with reduced kidney function; important drug-drug interactions involving these medications, particularly with other medications that are likely to be prescribed by nephrologists; and renal toxicities of antiretroviral agents.

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“…Reported side effects include lipodystrophy, hyperbilirrubinemia, gastrointestinal malaise, diarrhea and headache. Nephrolithiasis is the most common renal side effect, being reported in 4-9% of individuals [1], but the spectrum of renal and urinary adverse effects of IDV is much larger, as it can be appreciated in the case here presented.…”

mentioning

confidence: 55%

Indinavir-associated toxicity mimicking urinary tuberculosis in a patient with AIDS

et al. 2008

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This case reported to a patient with AIDS who presented persistent sterile leukocyturia and hematuria, lower back pain, bladder suffering symptoms, and renal papillary necrosis which were thought to be secondary to urinary tuberculosis but were demonstrated to be indinavir-associated side effects. The intention of this report is to remind medical professionals involved in the care of HIV+ patients of this possible association in order to avoid unnecessary investigation and to stress the need of careful periodical assessment of renal function and urinalysis in patients treated with indinavir.

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Changes in renal function associated with indinavir

Cited by 73 publications

References 10 publications

Population Pharmacokinetics of Indinavir in Patients Infected with Human Immunodeficiency Virus

Population Pharmacokinetics of Indinavir in Patients Infected with Human Immunodeficiency Virus

Highly Active Antiretroviral Therapy and the Kidney

Indinavir-associated toxicity mimicking urinary tuberculosis in a patient with AIDS

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