Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Indinavir”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed2001

Comparison of P-triglyceride levels among patients with human immunodeficiency virus on randomized treatment with ritonavir, indinavir or ritonavir/saquinavir.

This study compared the alterations in p-triglyceride (PT) in 111 protease inhibitor (PI)-naive patients on randomized treatment with either indinavir (800 mg 3 times daily), ritonavir (600 mg twice daily) or ritonavir/saquinavir (400 mg each twice daily) and 2 nucleoside reverse transcriptase inhibitors (NRTIs). PT (non-fasting) was measured at regular intervals until week 48. PT levels were evaluated in relation to PI regime, CD4 cell count and prior NRTI experience. The effect on PT levels of changing PI regime was analysed. For 24 patients fasting and non-fasting PT values were correlated. In the ritonavir-containing arms PT levels increased significantly (median PT at baseline: 1.80 mmol/l; week 36: 2.3 mmol/l; p < 0.001). In the indinavir arm no significant rise in PT levels was observed. Comparing the PI arms at week 48 showed significantly higher levels of PT in the ritonavir-containing arms than in the indinavir arm (p < 0.001). There was a high correlation between fasting and non-fasting PT values (p < 0.001, p = 0.88). A significant decline in PT values when changing PI treatment was observed (n = 13, p = 0.016). Ritonavir-containing regimens caused a rapid and sustained elevation of PT values, while indinavir did not significantly affect PT levels.

Anti-HIV Agents↗
PubMed2006

Indinavir-treated Cryptococcus neoformans promotes an efficient antifungal immune response in immunosuppressed hosts.

A previous paper demonstrated that indinavir affects the virulence of Cryptococcus neoformans, thereby rendering the fungus more susceptible to killing by natural effector cells. This study demonstrates that inoculation of immunosuppressed mice with C. neoformans previously exposed to indinavir, in comparison to untreated C. neoformans, results in: (i) a more pronounced secretion of interleukin-12 by splenic dendritic cells; (ii) reduction of CD14 and Fc gammaRs expression on splenic dendritic cells, and upregulation of CD86 and CD40 molecules; (iii) enhancement of interferon-y and interleukin-2 production by splenic T cells and increase of their proliferation in response to fungal antigens; and (iv) survival from an otherwise lethal challenge, correlated with a drastic decrease in colony forming units from brain and liver. In conclusion, these data indicate that indinavir interaction with C. neoformans could be beneficial because of its direct influence on fungal virulence and blunting of the deleterious effects exerted by C. neoformans on host immune response. Thus, indinavir could be crucial in addressing the outcome of cryptococcosis in immunocompromised hosts.

Animals↗
PubMed2002

Indinavir-induced cholelithiasis in a patient infected with human immunodeficiency virus.

We report the first case of acute cholecystitis due to indinavir-induced cholelithiasis in a patient infected with human immunodeficiency virus who had been receiving indinavir for 56 months. Infrared spectroscopy demonstrated that the gallstone was composed of indinavir monohydrate (50%), calcium bilirubinate (28%), calcium palmitate (10%), cholesterol (7%), and proteins (5%). The role of high-level chronic unconjugated hyperbilirubinemia coupled with high blood concentrations of indinavir is discussed.

Acute Disease↗
PubMed2004

Impact of indinavir on the quality of life in patients with advanced HIV infection treated with zidovudine and lamivudine.

OBJECTIVE: In AIDS Clinical Trial Group (ACTG) study 320, triple-combination antiretroviral therapy including indinavir significantly slowed progression to acquired immunodeficiency syndrome or death, compared with treatment with dual nucleoside reverse-transcriptase inhibitors (NRTIs) alone, in zidovudine-experienced patients with advanced human immunodeficiency virus (HIV) infection. We examined the impact of indinavir on quality of life in participants from this study. METHODS: A total of 1156 protease inhibitor- and lamivudine-naive patients stratified by CD4 cell count (<or=50 and 51-200 cells/mm(3)) were randomized to receive zidovudine (or stavudine) and lamivudine, with or without indinavir. Health-related quality of life was measured using the ACTG QoL601-602 questionnaire, which assesses general health status measured on a visual analogue scale and 8 specific health-related domains. Quality-adjusted survival time was estimated using the visual analogue scale for general health. RESULTS: Mean changes in general health scores after 24 weeks were +2.9 in the triple-therapy group versus -0.2 in the dual-therapy group (P=.018). By week 24, scores in all specific domains were higher with triple-drug therapy than dual-drug therapy, with statistically significant differences in role function, energy, and pain scores. Benefits of triple-drug therapy were largely confined to patients with CD4 cell counts of <or=50 cells/mm(3). Quality-adjusted survival time did not differ significantly between the 2 treatment groups. CONCLUSIONS: Triple-drug therapy with indinavir and 2 NRTIs resulted in a significant improvement in general health status after 24 weeks, especially in patients with low CD4 cell counts. Patients receiving triple-drug therapy also had significantly better role function, energy, and pain scores than did patients treated with dual-drug therapy.

Adult↗
PubMed1998

A pilot study of nevirapine, indinavir, and lamivudine among patients with advanced human immunodeficiency virus disease who have had failure of combination nucleoside therapy.

The effects of nevirapine, indinavir, and lamivudine in combination were studied among 22 human immunodeficiency virus (HIV)-infected patients with CD4 cell counts < or =50/mm3, whose options for antiretroviral therapy were limited by clinical or laboratory failure or toxicity with previous regimens. Median plasma HIV RNA was 5.16 log10 copies/mL at baseline, decreasing by a median of 3.12 log10 copies/mL at 24 weeks. Median baseline CD4 cell count was 30/mm3, increasing by a median of 95/mm3 at week 24. Adverse reactions led to drug discontinuation in 4 cases. Steady-state pharmacokinetic analysis in 17 patients was consistent with an interaction between nevirapine and indinavir. Nevirapine plasma levels were within the expected range, while indinavir levels were lower than expected. Despite this interaction, the combination of nevirapine, indinavir, and lamivudine was safe and well-tolerated and had substantial antiviral and immunologic effects lasting for the 24-week study.

Anti-HIV Agents↗
PubMed2001

Antiretroviral drug concentrations in semen of HIV-infected men: differential penetration of indinavir, ritonavir and saquinavir.

Variable drug penetration of antiretroviral drugs into the genital tract may contribute to the differential evolution of HIV and the emergence of drug resistance. This, in turn, may have an impact on the sexual transmission of resistant HIV in patients treated with antiretroviral drugs. We have measured concentrations of the HIV-1 protease inhibitors indinavir, ritonavir and saquinavir in the blood plasma (BP) and seminal plasma (SP) of 23 HIV-1-positive men. Forty-five time-matched blood and semen samples were obtained. SP concentrations of indinavir exceeded the EC95 of indinavir, corrected for protein binding, of 42 ng/mL at all time intervals. In contrast, the median ritonavir and saquinavir SP concentrations were below the relevant EC95 at all times post drug ingestion. The median SP:BP concentration ratios for indinavir were 0.6, 0.8 and 1.4, respectively, at 0-2, 2-6 and 6-8 h post-drug ingestion. In contrast, the median SP:BP concentration ratios at 0-3, 3-9 and 9-12 h post-drug ingestion were <0.02, <0.04 and <0.04, respectively, for both ritonavir and saquinavir. These differences justify further study of HIV-1 evolution and development of resistance in the genital tract of men taking these anti-HIV drugs.

Adult↗
PubMed2003

Changes in indinavir exposure over time: a case study in six HIV-1-infected children.

OBJECTIVE: To study changes in indinavir exposure over time in HIV-1-infected children. MATERIALS AND METHODS: Protease inhibitor (PI)-naive HIV-1-infected children were treated with indinavir, zidovudine and lamivudine. Steady-state plasma pharmacokinetic (PK) sampling was carried out as standard of care. The AUC(0-8) was targeted between 15 and 30 mg h/L. PK sampling was repeated after dosage adjustment until the AUC(0-8) reached target values. Patients were included when the time interval between PK samplings was > or =2 years and differences in dosage/m2 <10% between PK samplings 1 and 2. Corrections of dose for changes in body size were carried out. RESULTS: Six children were enrolled with a median age of 5.2 years (range 1.7-13.6 years). All had a viral load below 500 copies/mL. The geometric mean (GM) of the AUC(0-8) decreased from 25.3 mg h/L at the first PK-day to 19.1 mg h/L at the second PK-day [geometric mean ratio (GMR): 0.76 (95% C.I.: 0.48-1.20)]. The GM of Cmax decreased from 11.8 to 10.4 mg/L [GMR: 0.88 (95% C.I.: 0.59-1.32)]. The GM of Cmin decreased from 0.08 to 0.07 mg/L [GMR: 0.86 (95% C.I.: 0.62-1.18)]. All children had an AUC(0-8) above 15 mg h/L on the first PK-day; three had an AUC(0-8) below 15 mg h/L on the second PK-day. In two of these three children, the plasma viral load was >500 copies/mL. CONCLUSION: Changes in indinavir exposure were observed over time. In two patients, decreased indinavir exposure was associated with virological failure. Therapeutic drug monitoring should be carried out over time since this may prevent subtherapeutic dosing in children.

Adolescent↗
PubMed1998

Variation in incidence of indinavir-associated nephrolithiasis among HIV-positive patients.

BACKGROUND: Nephrolithiasis may be an important consequence of indinavir therapy; however little has been published on the variation in incidence between different populations of patients or the possible mechanisms of calculus formation. OBJECTIVE: To examine variation in the incidence of indinavir-associated nephrolithiasis (IAN) in HIV-positive patients in relation to hemophilia and hepatitis C virus (HCV) infection. METHODS: Clinical data were abstracted retrospectively from the medical records of all adult patients treated with indinavir from September 1995 to September 1997. Occurrence of first IAN, defined as flank pain and hematuria after initiation of therapy, was analyzed in relation to hemophilia status and HCV infection. RESULTS: There were 17 episodes of IAN (22%) among 79 patients treated with indinavir. Of 10 patients with hemophilia, 50% developed IAN as compared with 17% of patients without hemophilia (P = 0.03). Median days to first IAN was 22 (range 7-110 days) for hemophiliacs and 156 (range 5-611 days) for those without hemophilia. Data for HCV status were available for 74 out of 79 patients: 10 out of 27 (37%) patients with HCV developed IAN compared with six out of 42 (14%) without HCV (P = 0.02). CONCLUSION: Overall incidence of IAN was higher than that previously reported and was significantly greater in hemophiliacs than in non-hemophiliacs. HCV may be a contributing factor.

Adult↗
PubMed2001

Clinical outcome among HIV-infected patients starting saquinavir hard gel compared to ritonavir or indinavir.

OBJECTIVE: To compare the clinical response among patients who initiate protease inhibitor therapies with different virological potency. DESIGN: We analysed patients who started indinavir, ritonavir or saquinavir hard gel capsule (hgc) as part of at least triple therapy during prospective follow-up within the EuroSIDA study. METHODS: Changes in plasma viral load (pVL) and CD4 cell count from baseline were compared between treatment groups. Time to new AIDS-defining events and death were compared in Kaplan--Meier models, and Cox models were established to further assess differences in clinical progression (new AIDS/death). Adjustment was made for differences in baseline parameters, in particular pVL, CD4 cell count, and region of Europe. RESULTS: A total of 2708 patients (median follow-up: 30 months) were included, of which 556 started ritonavir (21%), 1342 indinavir (50%), and 810 saquinavir hgc (30%). The three groups were fairly evenly balanced at baseline regarding CD4 count, previous diagnosis of AIDS and pVL, After 12 months, the median changes in CD4 cell count were 90, 96 and 74 x 10(6) cells/l, respectively;P < 0.001, the proportions of patients with pVL < 500 copies/ml were 47, 54 and 41%; P < 0.001, and the proportions with clinical progression were 11.9, 9.2 and 11.9%, respectively; P = 0.20 (log-rank test). In multivariate models the relative risk of clinical progression for indinavir compared with saquinavir hgc was: 0.77 (0.60--0.99); P = 0.043, and for ritonavir 0.83 (0.62--1.11); P = 0.20. CONCLUSIONS: Saquinavir hgc was associated with an inferior long-term clinical response relative to indinavir, which was consistent with the observed differences in virological and immunological responses.

Administration, Oral↗
PubMed2001

Prospective evaluation of the effect of initiating indinavir-based therapy on insulin sensitivity and B-cell function in HIV-infected patients.

OBJECTIVE: To determine whether initiation of antiretroviral therapy that includes the protease inhibitor indinavir causes insulin resistance or abnormal B-cell function in study subjects with HIV infection. METHODS: Nonwasted, HIV-infected study subjects who did not have concurrent diabetes were prospectively evaluated by oral and intravenous glucose tolerance testing at baseline, at 2 weeks after starting indinavir monotherapy, and at another 6 weeks after initiating indinavir-based triple-therapy. RESULTS: Mean CD4 count at entry was 282 cells/microl and median HIV RNA was 33,000 copies/ml; all experienced a virologic response. Fasting glucose increased from 83.2 +/- 3.7 mg/dl at baseline to 86.8 +/- 3.2 at week 2 and 91.7 +/- 3.5 at week 8 (p =.003). Insulin sensitivity by minimal model analysis decreased by 30.5% over 8 weeks, from 3.83 +/- 0.63 min-1 per microU/ml x 10-4 to 3.09 +/- 0.53 at week 2 and 2.66 +/- 0.35 at week 8 (p =.01). Insulin secretion by the acute insulin response to intravenous glucose did not change (baseline 822 +/- 283 microU/ml x min, week 8 880 +/- 289; p = 0.4), and the insulin response to oral glucose (30 minute insulin:glucose ratio) fell from 1.69 +/- 0.54 microU/ml per mg/dl at baseline to 1.18 +/- 0.34 at week 8 (p =.05). CONCLUSION: During 8 weeks of indinavir-based therapy, fasting glucose increased and insulin sensitivity decreased, without a compensatory increase in insulin release. This combination of insulin resistance without augmented B-cell response may explain the hyperglycemia and other metabolic abnormalities seen in some protease inhibitor-treated patients.

Adult↗
PubMed2001

A pilot trial of indinavir, ritonavir, didanosine, and lamivudine in a once-daily four-drug regimen for HIV infection.

OBJECTIVE: To evaluate the tolerance, pharmacokinetics, and virologic and immunologic outcomes of once-daily indinavir, ritonavir, didanosine, and lamivudine in HIV-seropositive individuals. DESIGN: Open-label 24-week pilot study. PATIENTS: Ten HIV-seropositive subjects who were either antiretroviral-naive or minimally experienced with short-term single-or dual-nucleoside therapy provided informed consent and were enrolled. All subjects received didanosine (400 mg) 30 to 60 minutes before a meal followed by indinavir (1200 mg), ritonavir (400 mg), and lamivudine (300 mg) concurrent with the aforementioned meal. METHODS: Safety laboratory tests, including a complete blood cell count and amylase, lipase, liver transaminase, and nonfasting lipid monitoring as well as plasma HIV viral load and CD4+ lymphocyte count, were carried out at monthly intervals. Genotyping was performed at baseline. Pharmacokinetic studies for indinavir and ritonavir were performed at week 8. RESULTS: Nine of 10 subjects completed 24 weeks of therapy. No subject demonstrated primary protease inhibitor mutations at baseline. Toxicities experienced by subjects were typically mild and consistent with those commonly reported for each of the medications, including two cases of hematuria. By week 24, median nonfasting cholesterol and triglyceride levels increased by 49% and 108%, respectively. Median baseline plasma HIV viral load and CD4+ lymphocyte count were 29,292 (4.47 log10) copies/ml and 224 cells/mm3, respectively. Eight of 10 subjects had a plasma HIV viral load of <50 copies/ml by week 12. The 2 subjects with a detectable HIV viral load reached <50 copies/ml by week 28. Median CD4+ lymphocyte counts increased by 193 cells/mm3 at week 24. Indinavir and ritonavir plasma concentrations remained above respective inhibitory and effective concentrations (IC95 and EC50) (uncorrected for protein binding) throughout the 24-hour dosing interval for 6 of 10 and 8 of 10 subjects, respectively. CONCLUSIONS: Our pilot study demonstrates excellent virologic suppression despite low minimum protease inhibitor concentrations during a dosing interval in some patients and is supportive of further study.

Adult↗
PubMed2005

Steady-state pharmacokinetics and tolerability of indinavir-lopinavir/r combination therapy in antiretroviral-experienced patients.

Six HIV-positive antiretroviral experienced patients initiating therapy with a regimen including lopinavir/ritonavir (400/100 mg twice per day) and indinavir (800 mg twice per day) underwent steady-state pharmacokinetic analysis. The AUC0-12 h of indinavir when combined with lopinavir/ritonavir was comparable with previously published data on indinavir/ritonavir 800/100 mg twice per day in HIV-infected individuals. However, lopinavir AUC0-12 h, Cmax, and C12 h were lower than previously reported in the absence of indinavir. The regimen was well tolerated, although 2 patients developed grade 3 hypertriglyceridemia. No patient discontinued the regimen because of indinavir-related urologic or retinoid-type adverse effects. Further study of the regimen with larger cohorts of patients is necessary.

Adult↗
PubMed1997

Modeling of the change in CD4 lymphocyte counts in patients before and after administration of the human immunodeficiency virus protease inhibitor indinavir.

We investigated the relationships between changes in CD4 lymphocytes counts over 24 weeks after the initiation of therapy with indinavir at dosages of > or = 2.4 g/day (n = 15) in human immunodeficiency virus-positive patients and compared them to the baseline values. Starting CD4 count were linked to the time-weighted average CD4 cell count (return) through a nonlinear effect model. The diminution of destruction of CD4 cells after the initiation of indinavir therapy was estimated by fitting simultaneous differential equations to the data by using a linked lymph node (LN)-blood (BL) (two-compartment) system in which there is a constant rate of generation (R), first-order transfer rate constants (KLN-BL and KBL-LN) of compartment exchange, and first-order rate constants of CD4 destruction in the absence and presence of indinavir (KLN-OUT1 and KLN-OUT2). The half-life of CD4 lymphocytes was calculated from the rate constants by standard two-compartment methods. The CD4 lymphocyte counts at the start and return were linked in a sigmoid-Emax model were the maximal effect (Emax) was at 574.6 cells/microliters and 50% of the effect occurred at 157.1 cells/microliters (r2 = 0.94; P < 0.001). The mean +/- standard deviation (median) KLN-OUT2 was 0.574 +/- 0.202 (0.589), indicating that indinavir decrease the destruction of CD4 cells by circa 41 to 42%. The mean (median) CD4 half-life was 11.5 +/- 5.72 day (10.3 days). In multivariate analysis, KLN-OUT2 was significantly correlated with starting the CD4 cells count and the change in the CD4 cell count on therapy. The relationship between CD4 lymphocyte half-life and the starting CD4 lymphocyte count was hyperbolic, with a rapid increase in half-life as the CD4 count decreased. On the basis of the calculated half-life, the average production (destruction) of CD4 lymphocytes was approximately 3 x 10(9) cells/day, with an individual variation of 44-fold. These findings suggest that (i) the CD4 lymphocyte cell count at the start is significantly correlated to both the decrease in the destruction rate of CD4 cells and the degree of change in the CD4 lymphocytes on therapy, (ii) the lower the initial CD4 lymphocyte count, the higher the amount of CD4 lymphocyte turnover and the lower the ability of the immune system to increase absolute CD4 lymphocyte levels after viral suppression, consistent with a decreased regenerative capacity with progression of disease; and (iii) the increase in CD4 lymphocytes is likely secondary to the expansion of proliferating pool of cells since our determinations are based on 24 weeks of effect.

Anti-HIV Agents↗
PubMed2001

Pharmacological basis for concentration-controlled therapy with zidovudine, lamivudine, and indinavir.

Conventional antiretroviral therapy involves administration of standard fixed doses to adults and adolescents. This approach ignores interindividual variability in pharmacokinetics and results in substantial differences in systemic concentrations among patients. Thus, variability in systemic concentrations contributes to variability in response to therapy. This study was designed to evaluate the feasibility and safety of a regimen of zidovudine, lamivudine, and indinavir designed to achieve select target concentrations versus standard dose therapy. Twenty-four antiretroviral-naïve subjects completed the 24-week study; 13 received standard therapy, and 11 received concentration-controlled therapy. There were no differences in baseline characteristics. Oral clearance for all three drugs was not different between weeks 2 and 28; average ratios of week 2 oral clearance to week 28 oral clearance were 0.95, 1.09, and 1.06 for zidovudine, lamivudine, and indinavir, respectively, with 95% confidence intervals including 1. The selected target concentrations were average steady-state concentrations of 0.19 mg/liter for zidovudine and 0.44 mg/liter for lamivudine and a trough concentration of 0.15 mg/liter for indinavir; mean concentrations achieved at week 28 in the concentration-controlled arm were 0.20, 0.54, and 0.19 mg/liter, respectively. Concentration-controlled therapy significantly reduced interpatient variability in zidovudine concentrations and significantly increased indinavir concentrations. There was no difference in adverse drug effects or adherence. This investigation has provided a pharmacologic basis for concentration-controlled therapy by demonstrating that it is feasible and has a safety profile no different from that of standard therapy. Additional studies to evaluate the virologic effect of the concentration-controlled approach to antiretroviral therapy are warranted.

Adult↗
PubMed2002

Efficacy of zidovudine compared to stavudine, both in combination with lamivudine and indinavir, in human immunodeficiency virus-infected nucleoside-experienced patients with no prior exposure to lamivudine, stavudine, or protease inhibitors (novavir trial).

We compared the efficacy and the toxicity of zidovudine (AZT) versus stavudine (d4T), in combination with lamivudine (3TC) and indinavir, in AZT-, dideoxyinosine (ddI)-, and/or dideoxycytosine (ddC)-experienced patients in a randomized comparative multicenter trial. One hundred seventy human immunodeficiency virus type 1 (HIV-1)-infected patients, who had received AZT, ddI, and/or ddC for at least 6 months but were naive for d4T, 3TC, and protease inhibitors, were randomized to AZT at 250 to 300 mg twice daily, 3TC at 150 mg twice daily, and indinavir at 800 mg every 8 h or to d4T at 40 mg twice daily, 3TC at 150 mg twice daily, and indinavir at 800 mg every 8 h. The primary endpoint was time to virological failure, defined as plasma HIV-1 RNA levels of >5,000 copies/ml after at least 8 weeks of antiretroviral therapy. Additional endpoints were change from baseline in CD4 cell counts, AIDS-defining events and adverse events, and proportion of patients with HIV-1 RNA levels of <500 copies/ml and HIV-1 RNA levels of <50 copies/ml. At week 80, 15 patients in the AZT arm and 14 patients in the d4T arm had reached the primary endpoint, and time to virological failure did not differ between the two arms (P = 0.98). In the d4T and in the AZT arms, 67 and 73% of patients, respectively, had HIV-1 RNA levels of <500 copies/ml (P = 0.50). The median change from baseline in CD4 cell count was 195 x 10(6) and 175 x 10(6)/liter for the d4T- and AZT-containing arms, respectively. The proportions of patients with HIV-1 RNA levels of <50 copies/ml at weeks 8, 16, and 24 were similar in the two arms. The occurrence of serious adverse events was not significantly different between arms. In conclusion, in these patients heavily pretreated with AZT, switching from AZT to d4T when initiating indinavir and 3TC did not bring any additional benefit compared to maintaining AZT.

Adult↗
PubMed2004

Population pharmacokinetics of indinavir in patients infected with human immunodeficiency virus.

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 one-compartment 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 microg/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.

Adolescent↗
PubMed2000

Paronychia with pyogenic granuloma in a child treated with indinavir: the retinoid-mediated side effect theory revisited.

BACKGROUND: The introduction of HIV-1 protease inhibitors into the treatment of patients infected with HIV-1 has had a major influence on clinical practice. However, the use of protease inhibitors is frequently associated with the development of resistance and several side effects and interactions with other drugs have been reported. OBSERVATIONS: We present the first pediatric patient with paronychia with pyogenic granuloma associated with the administration of the protease inhibitor indinavir. Clinical findings are discussed in view of a possible interference of indinavir with endogenous retinoid metabolism. CONCLUSION: Considerable evidence advocates the mediation of indinavir side effects by impaired oxidative metabolism of retinoic acid through the inhibition of cytochromes P450 3A by indinavir rather than by impaired formation of 9-cis-retinoic acid.

Adolescent↗
PubMed1999

Urolithiasis and the protease inhibitor indinavir.

OBJECTIVE: To evaluate specific urological abnormalities in patients treated with the protease inhibitor indinavir. METHODS: A series of 155 consecutive human immunodeficiency virus-positive patients were treated with indinavir 800 mg p.o. three times a day. Of these, 14 (9%) treated for 1-321 (average 110) days experienced severe flank pain and were subjected to clinical and laboratory examinations. RESULTS: Abdominal X-ray was consistently negative for stones. Ultrasonography showed upper-tract dilatation in 12 patients. Intravenous urography showed obstruction above a radiolucent obstacle in 7 patients; in 2 cases, there was a marked delay in urine excretion on the obstructed side. The mean urine pH was 6. Urine culture was negative. Serum uric acid, phosphorus, and calcium levels were normal. In 8 patients there was slight renal insufficiency, and 4 patients required ureteral stenting. In all cases, hyperhydration and oral analgesia led to a favorable outcome. In 3 patients, chemical analysis of the stone demonstrated monohydrate indinavir crystals. CONCLUSIONS: In our experience, indinavir therapy is associated with urolithiasis in 9% of the cases. Hydration, analgesia, and acidification of the urine usually lead to a favorable clinical outcome. Prophylactic hydration and acidification of the urine are extremely important.

Adult↗