Plasma levels of voriconazole administered via a nasogastric tube to critically ill patients

Mohammedi, I.; Piens, Marie‐Antoinette; Padoin, Christophe; Robert, Dominique

doi:10.1007/s10096-005-1325-7

Cited by 24 publications

(23 citation statements)

References 12 publications

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“…Several published reports discuss the use of nasogastric and other types of enteral feeding tubes to administer azole antifungals, including fluconazole (1,14,19), itraconazole (15), and voriconazole (7,12,13).…”

Section: Discussionmentioning

confidence: 99%

“…A prospective observational study examined the pharmacokinetic effects of administering a suspension of crushed voriconazole tablets via nasogastric tube to eight mechanically ventilated ICU patients with suspected or documented IFIs (13). After a mean duration of 16 days of treatment, the means Ϯ 1 standard deviation of trough and peak voriconazole concentrations were 4.6 Ϯ 2.8 mg/liter and 6.4 Ϯ 4.3 mg/liter, respectively, higher than the mean peak voriconazole concentrations seen in another study of patients at risk from aspergillosis who were given 200 or 300 mg of voriconazole orally twice daily for 14 days (C max , 3.00 and 4.66 mg/liter, respectively) (package inserts for VFEND I.V.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics of Posaconazole Administered Orally or by Nasogastric Tube in Healthy Volunteers

Ashley

Varkey

Krishna³

et al. 2009

Antimicrob Agents Chemother

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The use of a nasogastric tube is one means of administering antifungal therapy to critically ill patients unable to receive medication via the oral route. This was a phase 1, open-label, single-center, randomized, crossover study of posaconazole administered via nasogastric tube in healthy volunteers. Each subject received two 400-mg single doses of posaconazole, one administered orally and one administered by nasogastric tube, with a 7-day washout period between each dose. Posaconazole was administered 5 to 10 min after subjects received a nutritional supplement. Blood samples for pharmacokinetic analysis were obtained up to 120 h postdose. The analysis of variance estimate of the study population suggests that the posaconazole nasogastric tube administration least-square mean values of observed maximum concentration (C max ), area under the plasma concentration-time curve (AUC) to the last measurable concentration, and AUC to time infinity were 81%, 76%, and 77%, respectively, of the corresponding oral administration values. The reason for lower C max and AUC values when posaconazole is administered via the nasogastric tube route is not known. Oral and nasogastric tube administration of a single 400-mg dose of posaconazole suspension was safe and well tolerated in healthy adult subjects. The incidence and nature of treatment-emergent adverse events were similar with both administration routes, and no serious adverse events or clinically significant laboratory test or vital sign abnormalities were reported. Obtaining plasma posaconazole concentrations may be warranted when posaconazole is given to patients via a nasogastric tube to ensure adequate posaconazole exposure. Strategies that have been shown to enhance posaconazole exposure (such as splitting the dose and minimizing the use of proton pump inhibitors) may also be used.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Posaconazole Administered Orally or by Nasogastric Tube in Healthy Volunteers

Ashley

Varkey

Krishna³

et al. 2009

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Similar to studies with other drugs, population pharmacokinetic investigations have shown that interpatient variability is more common in certain patient cohorts (12,27,55,59,60,65,82,90,91,92,102). For example, in a recent study of bone marrow transplant recipients receiving voriconazole for antifungal prophylaxis, 87 patients had voriconazole trough concentrations assayed after 5 days of therapy.…”

Section: -Fcmentioning

confidence: 94%

“…In this patient group, doses of 800 mg per day were needed to achieve detectable concentrations. In a much smaller study of critically ill patients in an intensive care unit setting, eight patients were administered 200 mg voriconazole by nasogastric tube twice daily (59). The mean trough concentration in the small cohort was 4.6 g/ml, but the variation was large.…”

Section: -Fcmentioning

confidence: 98%

Antifungal Therapeutic Drug Monitoring: Established and Emerging Indications

Andes

Pascual

Marchetti

2009

Antimicrob Agents Chemother

444

344

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“…The extreme intra-and interpatient variability in plasma concentrations in the context of established exposureresponse/toxicity relationships has triggered the need for therapeutic drug monitoring (TDM) in daily practice (1)(2)(3)(4). Extensive pharmacokinetic research has revealed several altering covariates, including CYP450-mediated drug-drug interactions (5), genetic polymorphism associated with the CYP2C19 enzyme (6), age (7)(8)(9), liver disease (10), coadministration of drug with food (11,12) or enteral feeding (13), and switching from intravenous to oral administration (1,14). As a result, inadequate responses or severe toxic events have been reported.…”

mentioning

confidence: 99%

Impact of Hypoalbuminemia on Voriconazole Pharmacokinetics in Critically Ill Adult Patients

Vanstraelen

Wauters

Vercammen

et al. 2014

Antimicrob Agents Chemother

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f Setting the adequate dose for voriconazole is challenging due to its variable pharmacokinetics. We investigated the impact of hypoalbuminemia (<35 g/liter) on voriconazole pharmacokinetics in adult intensive care unit (ICU) patients treated with voriconazole (20 samples in 13 patients) as well as in plasma samples from ICU patients that had been spiked with voriconazole at concentrations of 1.5 mg/liter, 2.9 mg/liter, and 9.0 mg/liter (66 samples from 22 patients). Plasma albumin concentrations ranged from 13.8 to 38.7 g/liter. Total voriconazole concentrations in adult ICU patients treated with voriconazole ranged from 0.5 to 8.7 mg/liter. Unbound and bound voriconazole concentrations were separated using high-throughput equilibrium dialysis followed by liquid chromatography-tandem mass spectrometry (LC-MSMS). Multivariate analysis revealed a positive relationship between voriconazole plasma protein binding and plasma albumin concentrations (P < 0.001), indicating higher unbound voriconazole concentrations with decreasing albumin concentrations. The correlation is more pronounced in the presence of elevated bilirubin concentrations (P ‫؍‬ 0.05). We therefore propose to adjust the measured total voriconazole concentrations in patients with abnormal plasma albumin and total serum bilirubin plasma concentrations who show adverse events potentially related to voriconazole via a formula that we developed. Assuming 50% protein binding on average and an upper limit of 5.5 mg/liter for total voriconazole concentrations, the upper limit for unbound voriconazole concentrations is 2.75 mg/liter. Alterations in voriconazole unbound concentrations caused by hypoalbuminemia and/or elevated bilirubin plasma concentrations cannot be countered immediately, due to the adult saturated hepatic metabolism. Consequently, increased unbound voriconazole concentrations can possibly cause adverse events, even when total voriconazole concentrations are within the reference range.

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Plasma levels of voriconazole administered via a nasogastric tube to critically ill patients

Cited by 24 publications

References 12 publications

Pharmacokinetics of Posaconazole Administered Orally or by Nasogastric Tube in Healthy Volunteers

Pharmacokinetics of Posaconazole Administered Orally or by Nasogastric Tube in Healthy Volunteers

Antifungal Therapeutic Drug Monitoring: Established and Emerging Indications

Impact of Hypoalbuminemia on Voriconazole Pharmacokinetics in Critically Ill Adult Patients

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