Effect of omeprazole on the pharmacokinetics of saquinavir-500 mg formulation with ritonavir in healthy male and female volunteers

  title={Effect of omeprazole on the pharmacokinetics of saquinavir-500 mg formulation with ritonavir in healthy male and female volunteers},
  author={Alan Winston and David Back and Carl Fletcher and Lesley Robinson and Jennifer Unsworth and Izabela Tolowinska and Malte Schutz and Anton L. Pozniak and Brian George Gazzard and Marta Boffito},
Introduction:Recent studies have described reduced absorption of certain protease inhibitors when administered with agents known to increase gastric pH. No clinically significant interactions between saquinavir absorption and gastric pH have previously been shown. We evaluated the effect of omeprazole, a proton-pump-inhibitor, on the pharmacokinetics of the recently developed saquinavir-500 mg formulation co-administered with ritonavir. Methods:Eighteen healthy subjects (n = 6 women and 12 men… 

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

  • H. TappouniJ. Rublein A. Kashuba
  • Medicine
    American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
  • 2008
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 indinvir.

Pharmacokinetic Interaction between Darunavir Boosted with Ritonavir and Omeprazole or Ranitidine in Human Immunodeficiency Virus-Negative Healthy Volunteers

Investigation of the effect of ranitidine and omeprazole on the plasma pharmacokinetics of DRV and RTV in HIV-negative healthy volunteers found it well tolerated, and no serious adverse events were reported.

Pharmacokinetic Study of Saquinavir 500 mg Plus Ritonavir (1000/100 mg Twice a Day) in HIV-Positive Pregnant Women

Although PK parameters in week 24 and postpartum were very similar, those for week 34 showed an important reduction, compared with week 24, but no statistically significant differences were shown between patients.

Pharmacokinetics and Safety of Saquinavir/Ritonavir and Omeprazole in HIV‐infected Subjects

In the presence of omeprazole, saquinavir plasma exposure is significantly increased in HIV‐infected subjects whether administered simultaneously or 2 h apart, whereas staggered administration significantly increased saquinvir AUC0−12, Ctrough, and Cmax.

Lack of effect of gastric acid-reducing agents on the pharmacokinetics of lopinavir/ritonavir in HIV-infected patients.

HIV-infected patients who received gastric acid-reducing agents during administration of lopinavir/ritonavir-based treatment regimens did not appear to have a reduction in lopinvir or ritonavir exposures.

A pharmacokinetic study of etravirine (TMC125) co-administered with ranitidine and omeprazole in HIV-negative volunteers.

Rinitidine slightly decreased etravirine exposure, whereas omeprazole increased it by approximately 41%, which is attributed to CYP2C19 inhibition.

Coadministration of Esomeprazole With Fosamprenavir Has No Impact on Steady-State Plasma Amprenavir Pharmacokinetics

FPV 1400 mg bid or FPV 700 mg bid + RTV 100 mg bid may be coadministered simultaneously with ESO without dose adjustment, however, the impact of staggered administration of proton pump inhibitors (PPI) on plasma amprenavir exposure is unknown at present.

Exploring the Effect of Esomeprazole on Gastric and Duodenal Fluid Volumes and Absorption of Ritonavir

The data suggest that the PPI esomeprazole lowers the available fluid volume for dissolution, which may limit the amount of ritonavir that can be absorbed, which should be considered when simulating the absorption of poorly soluble drugs in real-life conditions.

Food consumption, cytochrome P450 3A4 (CYP3A4) presystemic inhibitors, and bioavailability of saquinavir.

  • P. Amariles
  • Medicine, Biology
    Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria
  • 2007

Pharmacokinetic Drug Interaction Profiles of Proton Pump Inhibitors: An Update

Data suggest that coadministration of PPIs with methotrexate may affect metotrexate pharmacokinetics, although the mechanism of interaction is not well understood and the potential for drug interactions should be considered when choosing a PPI to manage gastric acid-related disorders.



Pharmacokinetics of saquinavir co-administered with cimetidine.

Increased exposure to saquinavir was observed in healthy volunteers after co-administration with cimetidine and the most significant increase involved C(max), and further pharmacokinetic studies in HIV-infected subjects are warranted.

Interindividual variability of once-daily ritonavir boosted saquinavir pharmacokinetics in Thai and UK patients.

The ritonavir AUC and study site appeared to be related to exposure of saquinavir, and higher saquinvir A UCs, maximum concentrations and minimum concentrations were seen in Thai patients than in UK patients.

Effect of Antacids and Ranitidine on the Single-Dose Pharmacokinetics of Fosamprenavir

MAALOX TC and ranitidine decreased the area under the concentration-time curve for plasma amprenavir (APV) by 18% and the maximum concentration of drug in serum (Cmax) by 35% and caution is recommended when FPV is coadministered with histamine2- receptor antagonists or proton pump inhibitors.

Impact of gastric acid suppressants on cytochrome P450 3A4 and P-glycoprotein: consequences for FK506 assimilation.

Switching treatment with cimetidine to omeprazole in renal transplant recipients is associated with a decrease of dose/weight normalized trough levels of tacrolimus, and studies in healthy volunteers suggest that this may be explained by an increase of intestinal CYP3A4 activity.

Nonlinear kinetics after high‐dose omeprazole caused by saturation of genetically variable CYP2C19

High‐dose treatment with omeprazole uncovers saturation kinetics for CYP2C19 pathways in EMs, and CYP3A becomes the predominant enzyme of omepazole elimination, and these individuals may be at risk for side effects if high‐dose ometrazole treatment is combined with drugs inhibiting CYP 3A activity.

A Prospective Study of Efficacy and Safety of Once-Daily Saquinavir/Ritonavir plus Two Nucleoside Reverse Transcriptase Inhibitors in Treatment-Naive Thai Patients

First-line highly active antiretroviral therapy (HAART) with once-daily saquinavir/ritonavir plus two NRTIs showed strong antiviral efficacy over 24 weeks, and should be evaluated in larger prospective randomized clinical trials.

Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures

ATV boosted with RTV is as effective and well tolerated as LPV/RTV in treatment-experienced patients, with a more favorable impact on serum lipids and Pharmacokinetically enhanced ATV provides a suitable choice for therapy of treatment- Experienced HIV-infected patients.

Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms.

Since its inhibition is very potent and has a broad "window of selectivity," omeprazole seems to be a useful, selective inhibitor of CYP2C19, and lansoprazole may be the more important in vitro inhibitor of CyP2D6.

Sex-based differences in saquinavir pharmacology and virologic response in AIDS Clinical Trials Group Study 359.

Higher saquinavir AUC and C(min) values were associated with a greater likelihood of human immunodeficiency virus (HIV) RNA levels and were better predictors of response than was the saquinvir inhibitory quotient.