Trial reportAntimicrobial agents and chemotherapy2007
Steady-state pharmacokinetic and safety profiles of voriconazole and ritonavir in healthy male subjects.
Trial report in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Observational study of the clinical efficacy of voriconazole and its relationship to plasma concentrations in patients.Antimicrobial agents and chemotherapy · 2011Pooled it
- Time Course of the Interaction Between Oral Short-Term Ritonavir Therapy with Three Factor Xa Inhibitors and the Activity of CYP2D6, CYP2C19, and CYP3A4 in Healthy Volunteers.Clinical pharmacokinetics · 2024Trial
- Pharmacokinetic interaction of vicriviroc with other antiretroviral agents: results from a series of fixed-sequence and parallel-group clinical trials.Clinical pharmacokinetics · 2011Trial
- Oxycodone concentrations are greatly increased by the concomitant use of ritonavir or lopinavir/ritonavir.European journal of clinical pharmacology · 2010Trial
- The Effects of Ritonavir on the Pharmacokinetics of Tofacitinib in Rats.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Development of a physiologically-based pharmacokinetic model for Ritonavir characterizing exposure and drug interaction potential at both acute and steady-state conditions.CPT: pharmacometrics & systems pharmacology · 2025Article
- A case report of drug-drug interaction between voriconazole and simnotrelvir/ritonavir.Frontiers in antibiotics · 2025Article
- Unexpected voriconazole toxicity due to nirmatrelvir/ritonavir: a case report on drug-drug interaction and the role of therapeutic drug monitoring.Frontiers in pharmacology · 2025Article
- Physiologically-based pharmacokinetic modeling predicts the drug interaction potential of GLS4 in co-administered with ritonavir.CPT: pharmacometrics & systems pharmacology · 2024Article
- Atazanavir Resensitizes Candida auris to Azoles.Antimicrobial agents and chemotherapy · 2023Article
- A literature review of liver function test elevations in rifampin drug-drug interaction studies.Clinical and translational science · 2022Review
- A Mechanistic Absorption and Disposition Model of Ritonavir to Predict Exposure and Drug-Drug Interaction Potential of CYP3A4/5 and CYP2D6 Substrates.European journal of drug metabolism and pharmacokinetics · 2022Article
- A Physiologically Based Pharmacokinetic Model of Voriconazole Integrating Time-Dependent Inhibition of CYP3A4, Genetic Polymorphisms of CYP2C19 and Predictions of Drug-Drug Interactions.Clinical pharmacokinetics · 2020Article
- Identification of Cytochrome P450-Mediated Drug-Drug Interactions at Risk in Cases of Gene Polymorphisms by Using a Quantitative Prediction Model.Clinical pharmacokinetics · 2018Article
- Pharmacokinetic Interaction Between Isavuconazole and a Fixed-Dose Combination of Lopinavir 400 mg/Ritonavir 100 mg in Healthy Subjects.Clinical pharmacology in drug development · 2017Article
- Reliability and extension of quantitative prediction of CYP3A4-mediated drug interactions based on clinical data.The AAPS journal · 2014Article
- Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype dependent.The pharmacogenomics journal · 2014Article
- Clinically relevant drug-drug interactions between antiretrovirals and antifungals.Expert opinion on drug metabolism & toxicology · 2014Review
- Therapeutic drug monitoring of voriconazole: a case report of multiple drug interactions in a patient with an increased CYP2C19 activity.AIDS research and therapy · 2014Article
- Impact of genetic polymorphism on drug-drug interactions mediated by cytochromes: a general approach.The AAPS journal · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since there is a likelihood of coadministration of voriconazole and ritonavir, two studies were conducted to evaluate the potential of drug interaction. Study A was a randomized, placebo-controlled, two-period, parallel-group trial (n = 34). Study B had the same design without the placebo group (n = 17). In period 1, subjects received 200 mg voriconazole or placebo twice daily (BID) for 3 days (400 mg BID on day 1). In period 2, following a 7-day washout, subjects received ritonavir alone at 400 mg BID (study A) or 100 mg BID (study B) for 10 days (days 11 to 20), and then ritonavir was coadministered with 200 mg BID voriconazole or placebo for the next 10 days (days 21 to 30). Serial plasma samples were collected on days 3, 20, and 30, and safety data were collected throughout the study. High-dose (400 mg BID) ritonavir substantially reduced the steady-state mean voriconazole exposure (area under the concentration-time curve from 0 to 12 h [AUC(0-12)], -82%; maximum concentration [C(max)], -66%). However, the effect of low-dose (100 mg BID) ritonavir was less pronounced (AUC(0-12), -39%; C(max), -24%). The decrease in voriconazole exposure was probably due to the induction of CYP2C19 and CYP2C9 by ritonavir. It is interesting that one subject in each study exhibited the opposite effect of ritonavir on voriconazole exposure (a 2.5- to 3-fold increase), probably due to lack of CYP2C19. Voriconazole had no apparent effect on the exposure of high-dose ritonavir but slightly decreased the exposure of low-dose ritonavir (AUC(0-12), -14%; C(max), -24%). The safety profile of combination therapy was not notably different from that of voriconazole or ritonavir alone. Due to the significant effect of ritonavir on voriconazole exposure, coadministration of voriconazole with 400 mg BID ritonavir is contraindicated; coadministration with 100 mg BID ritonavir should be avoided, unless an assessment of the benefit/risk to the patient justifies the use.
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