Indinavir Concentrations and Antiviral Effect

Acosta, Edward P.; Henry, Keith; Baken, Leslie; Page, Linda M.; Fletcher, Courtney V.

doi:10.1592/phco.19.9.708.31544

Cited by 161 publications

(102 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the placebo group (indinavir 800 mg alone), indinavir pharmacokinetics varied significantly but was consistent with previously reported pharmacokinetic data. 1 Indinavir's AUC values in our study ranged from 13.7 to 68.7 mg · hr/L and C max values ranged from 7,000 to 25,900 ng/mL. However, these values were similar to or slightly higher than the indinavir AUC values reported under steady-state conditions.…”

Section: Discussioncontrasting

confidence: 56%

Effect of omeprazole on the plasma concentrations of indinavir when administered alone and in combination with ritonavir

Tappouni

Rublein

Donovan

et al. 2008

American Journal of Health-System Pharmacy

View full text Add to dashboard Cite

Purpose-The effects of omeprazole on indinavir when administered alone or in combination with ritonavir were evaluated.Methods-Fourteen men and women age 18-55 years not infected with human immunodeficiency virus who met study qualifications were randomized to receive placebo, 20 mg of omeprazole, or 40 mg of omeprazole daily. After seven days, the single-dose pharmacokinetic profile of an 800-mg dose of indinavir alone or in combination with 200 mg of ritonavir was evaluated. Study participants received each of four study regimens in one of four randomly assigned orders. Blood samples were collected, and plasma indinavir and ritonavir concentrations were analyzed using high-performance liquid chromatography. Conclusion-The AUC of indinavir was substantially decreased in healthy volunteers who received omeprazole 20 or 40 mg daily for seven days before the administration of a single 800-mg dose of indinavir. Concomitant administration of ritonavir 200 mg with indinavir in participants receiving omeprazole led to a significant increase in the AUC of indinavir. Results-The Index termsAntiretroviral agents; Blood levels; Dosage; Drug interactions; Gastrointestinal drugs; HIV infections; Indinavir; Omeprazole; Pharmacokinetics; Ritonavir Protease inhibitors (PIs) exhibit a high degree of pharmacokinetic variability in patients infected with the human immunodeficiency virus (HIV). 1,2 Large interindividual differences in drug absorption and elimination in HIV-infected patients have been primarily attributed to constitutive or altered drug metabolizing enzymes, P-glycoprotein transporter activities, and poor drug solubility. 3 With the PIs indinavir and atazanavir, changes in gastric pH can alter drug absorption. 4,5 Specifically, when these PIs are administered with medications that Address correspondence to Dr. Kashuba at the School of Pharmacy, CB7360, University of North Carolina, Chapel Hill, NC 27599-7360 (akashuba@unc.edu increase gastric pH, such as histamine (H 2 )-receptor antagonists and proton-pump inhibitors (PPIs), bioavailability can decrease by up to 76%. 4,6 A survey of 200 HIV-infected patients was performed to assess their use of drugs that affect gastric acidity. 7 Fifty-six percent of HIV-infected patients who had recently begun highly active antiretroviral therapy (HAART) had taken nonprescription acid-reducing agents, and 39% had used both nonprescription and prescription products for acid reduction. Forty-six percent of patients on a PI-containing regimen had used PPIs or H 2 -receptor antagonists once they started HAART, and 35% had used them within the previous 12 months. This widespread use of acid-reducing agents among HIV-infected patients has implications for drug interactions with antiretrovirals and other medications that require an acidic environment for adequate dissolution and absorption.Ritonavir is a cytochrome P-450 (CYP) isoenzyme 3A and P-glycoprotein inhibitor which, when used in low doses, can increase the exposure of concomitantly administered PIs. The concomitant ad...

show abstract

Section: Discussioncontrasting

confidence: 56%

Effect of omeprazole on the plasma concentrations of indinavir when administered alone and in combination with ritonavir

Tappouni

Rublein

Donovan

et al. 2008

American Journal of Health-System Pharmacy

View full text Add to dashboard Cite

show abstract

“…The impact of low plasma C min on clinical effectiveness of PI-containing regimens is uncertain, although a correlation has been observed between viral load after 12 weeks of therapy and C min . 22 It was observed that children who were Ͼ25 kg and treated TID (with or without NVP) had mean C min values exceeding adult values, although 8 of 30 patients (27%) did not have trough values Ͼ1000 g/L.…”

Section: Discussionmentioning

confidence: 95%

Nelfinavir Pharmacokinetics in Stable Human Immunodeficiency Virus-Positive Children: Pediatric AIDS Clinical Trials Group Protocol 377

et al. 2003

View full text Add to dashboard Cite

ABSTRACT. Objective. Pharmacokinetic data obtained from children who have human immunodeficiency virus (HIV) infection are essential for the safe and effective use of antiretroviral agents in pediatric populations. The objective of this study was to assess the impact of body weight on the pharmacokinetic disposition of nelfinavir (NFV) in the absence and presence of nevirapine (NVP) and compare the pharmacokinetic profiles of twice-daily (BID) and three-times-daily (TID) NFV regimens.Methods. This was an intensive pharmacokinetic substudy nested in a phase II, multicenter, randomized, open-label trial. Forty-five HIV-infected children receiving NFV 30 mg/kg TID and 6 HIV-infected children receiving NFV 55 mg/kg BID were enrolled in this study and assigned to 1 of 4 stavudine-containing regimens, 3 containing NFV and 2 containing NVP. Area under the plasma concentration-time curves from 0 to 8 hours (AUC 0 -8 hours ) and from 0 to 12 hours (AUC 0 -12 hours ) for the TID and BID regimens, respectively, were determined. For comparative purposes, the AUC 0 -24 hours was also calculated for each regimen.Results. NFV exposure in the absence of NVP was decreased in children who were <25 kg compared with those who were >25 kg (a 2.6-fold difference in median AUC 0 -8 hours ). NFV pharmacokinetics in the presence of NVP did not differ between the <25 kg and >25 kg groups. The AUC 0 -24 hours for children who were <30 kg and on NFV BID was comparable to the AUC 0 -24 hours for children who were >25 kg and on NFV TID but was 2.7-fold greater than AUC 0 -24 hours for children who were <25 kg and on NFV TID.Conclusions. NFV in the absence of NVP resulted in less than half the drug exposure in children who were <25 kg compared with children who were >25 kg. NFV dosed at 55 mg/kg BID in children who are <30 kg provides comparable exposure to that measured in children who are >25 kg and receiving NFV 30 mg/kg TID. Pediatrics 2003;112:e220 -e227. URL: http://www. pediatrics.org/cgi/content/full/112/3/e220; pharmacokinetics, nelfinavir, children, HIV, protease inhibitor, nevirapine.

show abstract

“…The long-term success of ARV treatment depends upon maintaining inhibitory concentrations of active drug at the site of HIV replication sufficient to suppress viral replication. Reduced serum levels of ARV drugs correlate with treatment failure and the development of ARV drug resistance [39][40][41][42]. High serum levels of ARV drugs have been shown to correspond with an increased incidence of [26][27][28] Some patients were issued with warnings for more than one adverse effect or interaction.…”

Section: Discussionmentioning

confidence: 99%

Potential health risks of complementary alternative medicines in HIV patients

et al. 2008

View full text Add to dashboard Cite

To determine the prevalence and purpose of complementary alternative medicines (CAMs) use in people receiving treatment for HIV infection. To identify and quantify potential health risks of CAM use in this population and to explore options for improved pharmacovigilance. MethodsCross-sectional questionnaire survey of 293 patients receiving antiretroviral (ARV) therapy at three specialist HIV out-patient clinics in central London, UK. The use of herbal medicines and supplements was explored, and potentially adverse side effects or significant drug interactions with conventional therapies were identified. ResultsOf the 293 patients included, 61% (n 5 179) were taking herbal remedies or supplements and 35% (n 5 103) were using physical treatments. Twenty-seven per cent (n 5 80) used a combination of both. Twenty per cent (n 5 59) potentially compromised their HIV management through using CAM therapy. Ten per cent (n 5 29) were advised to stop their CAMs and 15% (n 5 43) were made aware of potential drug interactions and adverse effects and were advised to monitor their care. ConclusionsThere are potentially significant health risks posed by the concomitant use of CAMs in patients taking ARV therapy. Medical practitioners need to be able to identify CAM use in HIV-positive patients and recognize potential health risks. Patients should be encouraged to disclose CAM use to their clinicians and other healthcare professionals.

show abstract

Indinavir Concentrations and Antiviral Effect

Cited by 161 publications

References 17 publications

Effect of omeprazole on the plasma concentrations of indinavir when administered alone and in combination with ritonavir

Effect of omeprazole on the plasma concentrations of indinavir when administered alone and in combination with ritonavir

Nelfinavir Pharmacokinetics in Stable Human Immunodeficiency Virus-Positive Children: Pediatric AIDS Clinical Trials Group Protocol 377

Potential health risks of complementary alternative medicines in HIV patients

Contact Info

Product

Resources

About