P1293 Comparison of plasma trough concentrations of voriconazole in patients with or without comedication of ranitidine or pantoprazole

Heinz, Werner; Kloeser, C.; Helle, A.; Guhl, C; Scheuermann, Stefan; Einsele, Herman; Klinker, Hartwig

doi:10.1016/s0924-8579(07)71133-0

Cited by 4 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar results were reported in many studies (Purkins et al, 2003b;Wood et al, 2003;Heinz et al, 2007;Andrews et al, 2008;Yasu et al, 2016) that demonstrated the effect of CYP2C19 and CYP3A4 inhibition has been evaluated over the PK of voriconazole and reported the increment of the AUC and C max of voriconazole. Table 4 represents the increment in AUC and C max of voriconazole due to inhibition of CYP isoenzyme by ethinyloestradiol and norethindrone (Andrews et al, 2008), cimetidine and ranitidine (Purkins et al, 2003b), omeprazole (Wood et al, 2003), pantoprazole (Heinz et al, 2007), lansoprazole (Yasu et al, 2016), esomeprazole (Bouatou et al, 2014), tacrolimus (Mochizuki et al, 2015), haloperidol (Motta et al, 2016), etravirine (Kakuda et al, 2013), azithromycin and erythromycin (Purkins et al, 2003d).…”

Section: Discussionsupporting

confidence: 87%

Pharmacokinetic interaction of voriconazole and clarithromycin in Pakistani healthy male volunteers: a single dose, randomized, crossover, open-label study

Mushtaq¹,

Fatima²,

Ahmad³

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

Background: Voriconazole an antifungal drug, has a potential for drug-drug interactions (DDIs) with administered drugs. Clarithromycin is a Cytochromes P450 CYP (3A4 and 2C19) enzyme inhibitor, and voriconazole is a substrate and inhibitor of these two enzymes. Being a substrate of the same enzyme for metabolism and transport, the chemical nature and pKa of both interacting drugs make these drugs better candidates for potential pharmacokinetic drug-drug interactions (PK-DDIs). This study aimed to evaluate the effect of clarithromycin on the pharmacokinetic profile of voriconazole in healthy volunteers.Methods: A single oral dose, open-label, randomized, crossover study was designed for assessing PK-DDI in healthy volunteers, consisting of 2 weeks washout period. Voriconazole, either alone (2 mg × 200 mg, tablet, P/O) or along with clarithromycin (voriconazole 2 mg × 200 mg, tablet + clarithromycin 500 mg, tablet, P/O), was administered to enrolled volunteers in two sequences. The blood samples (approximately 3 cc) were collected from volunteers for up to 24 h. Plasma concentrations of voriconazole were analyzed by an isocratic, reversed-phase high-performance-liquid chromatography ultraviolet-visible detector (RP HPLC UV-Vis) and a non-compartmental method.Results: In the present study, when voriconazole was administered with clarithromycin versus administered alone, a significant increase in peak plasma concentration (Cmax) of voriconazole by 52% (geometric mean ratio GMR: 1.52; 90% CI 1.04, 1.55; p = 0.000) was observed. Similarly, the area under the curve from time zero to infinity (AUC0-∞) and the area under the concentration-time curve from time zero to time-t (AUC0-t) of voriconazole also significantly increased by 21% (GMR: 1.14; 90% CI 9.09, 10.02; p = 0.013), and 16% (GMR: 1.15; 90% CI 8.08, 10.02; p = 0.007), respectively. In addition, the results also showed a reduction in the apparent volume of distribution (Vd) by 23% (GMR: 0.76; 90% CI 5.00, 6.20; p = 0.051), and apparent clearance (CL) by 13% (GMR: 0.87; 90% CI 41.95, 45.73; p = 0.019) of voriconazole.Conclusion: The alterations in PK parameters of voriconazole after concomitant administration of clarithromycin are of clinical significance. Therefore, adjustments in dosage regimens are warranted. In addition, extreme caution and therapeutic drug monitoring are necessary while co-prescribing both drugs.Clinical Trial Registration:clinicalTrials.gov, Identifier NCT05380245.

show abstract

Section: Discussionsupporting

confidence: 87%

Pharmacokinetic interaction of voriconazole and clarithromycin in Pakistani healthy male volunteers: a single dose, randomized, crossover, open-label study

Mushtaq¹,

Fatima²,

Ahmad³

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Based on in vitro findings pantoprazole is a weak inhibitor of CYP2C19 compared to other proton pump inhibitors (PPI), such as omeprazole . However, in vivo studies show that pantoprazole use can lead to a significant increase in C trough,ss of voriconazole. Moreover, benefits from TDM of voriconazole were greater in the patients who were cotreated with PPI at dosages ≥40 mg intravenously .…”

Section: Discussionmentioning

confidence: 99%

Optimization of Voriconazole Therapy for the Treatment of Invasive Fungal Infections in Adults

Mangal

Hamadeh

Arwood

et al. 2018

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

Therapeutic concentrations of voriconazole in invasive fungal infections (IFIs) are ensured using a drug monitoring approach, which relies on attainment of steady-state pharmacokinetics. For voriconazole, time to reach steady state can vary from 5-7 days, not optimal for critically ill patients. We developed a population pharmacokinetic/pharmacodynamic model-based approach to predict doses that can maximize the net benefit (probability of efficacy-probability of adverse events) and ensure therapeutic concentrations, early on during treatment. The label-recommended 200 mg voriconazole dose resulted in attainment of targeted concentrations in ≥80% patients in the case of Candida spp. infections, as compared to only 40-50% patients, with net benefit ranging from 5.8-61.8%, in the case of Aspergillus spp. infections. Voriconazole doses of 300-600 mg were found to maximize the net benefit up to 51-66.7%, depending on the clinical phenotype (due to CYP2C19 status and pantoprazole use) of the patient and type of Aspergillus infection.

show abstract

“…While pantoprazole and rabeprazole are generally expected to have a lower drug interaction potential than omeprazole (3), all proton pump inhibitors are known to competitively inhibit CYP2C19 activity in vitro (16). A previous report by Heinz et al demonstrated higher voriconazole concentrations when coadministered with pantoprazole (11). The lower regression coefficient determined for pantoprazole (Table 3) suggests a reduced (but still significant) interaction with voriconazole compared with those of other proton pump inhibitors, in agreement with in vitro findings that pantoprazole is the weakest inhibitor of CYP2C19 (16).…”

Section: Discussionmentioning

confidence: 99%

Multicenter Study of Voriconazole Pharmacokinetics and Therapeutic Drug Monitoring

Dolton

Ray

Chen

et al. 2012

Antimicrob Agents Chemother

252

272

View full text Add to dashboard Cite

P1293 Comparison of plasma trough concentrations of voriconazole in patients with or without comedication of ranitidine or pantoprazole

Cited by 4 publications

References 0 publications

Pharmacokinetic interaction of voriconazole and clarithromycin in Pakistani healthy male volunteers: a single dose, randomized, crossover, open-label study

Pharmacokinetic interaction of voriconazole and clarithromycin in Pakistani healthy male volunteers: a single dose, randomized, crossover, open-label study

Optimization of Voriconazole Therapy for the Treatment of Invasive Fungal Infections in Adults

Multicenter Study of Voriconazole Pharmacokinetics and Therapeutic Drug Monitoring

Contact Info

Product

Resources

About