Aqueous and Vitreous Concentrations Following Topical Administration of 1% Voriconazole in Humans

Abstract

To determine the penetration of 1% voriconazole solution into the aqueous and vitreous following topical administration.Methods: A prospective nonrandomized study of 13 patients scheduled for pars plana vitrectomy surgery. Aqueous and vitreous samples were obtained and analyzed after topical administration of 1% voriconazole every 2 hours for 24 hours before surgery. Drug concentration quantitation was performed using high-performance liquid chromatography. Results:The mean (SD) sampling time after topical administration of the last voriconazole dose was 24 ( 14) minutes. The mean (SD) voriconazole concentrations in the aqueous and vitreous were 6.49 (3.04) µg/mL and

Stability of extemporaneously prepared voriconazole ophthalmic solution

“…4 A recent study of the use of 1% voriconazole ophthalmic solution as monotherapy in patients undergoing elective eye surgery demonstrated that the concentration of voriconazole in the aqueous humor of the eye was sufficiently high to treat some types of fungal infections but may be inadequate for deep-seated infections that may involve, for example, the vitreous humor of the eye. 16 This finding is similar to that of a recent report by Vemulakonda et al, 17 who studied the penetration of a topically administered 1% voriconazole solution into the eye. The results of these studies suggest that a higher concentration of voriconazole ophthalmic solution (e.g., 2%) may be required to achieve adequate levels of voriconazole in the eye.…”

Stability of extemporaneously prepared voriconazole ophthalmic solution

“…4 A recent study of the use of 1% voriconazole ophthalmic solution as monotherapy in patients undergoing elective eye surgery demonstrated that the concentration of voriconazole in the aqueous humor of the eye was sufficiently high to treat some types of fungal infections but may be inadequate for deep-seated infections that may involve, for example, the vitreous humor of the eye. 16 This finding is similar to that of a recent report by Vemulakonda et al, 17 who studied the penetration of a topically administered 1% voriconazole solution into the eye. The results of these studies suggest that a higher concentration of voriconazole ophthalmic solution (e.g., 2%) may be required to achieve adequate levels of voriconazole in the eye.…”

Penetration of 1% voriconazole eye drops into human vitreous humour: a prospective, open‐label study

“…Accordingly, vitreous clearance of voriconazole seems to be completed within this time interval as no accumulation of voriconazole in the vitreous humour could be detected with this regime (total of 12 doses in this study). This observation may offer a possible answer to the questions raised by Vemulakonda et al 12 about how rapidly topically administered voriconazole is cleared from the eye and how long the levels remain in the therapeutic range following repeated dosing.…”

“…8 These are consistent with results from Hariprasad et al who reported levels of 1.1 Ϯ 0.6 mg/mL in aqueous humour following oral administration (sampled 2.9 Ϯ 0.5 h post dose) 13 , and Vemulakonda et al of 6.49 Ϯ 3.04 mg/mL (sampled 24 Ϯ 14 min post dose) following topical administration. 12 Although this study is limited by the small sample size, the results suggest that hourly application of 1% voriconazole eye drops is likely to produce concentrations that are adequate to treat infections associated with most sensitive Candida species in the posterior chamber, but is of little value when other species such as Aspergillus or Fusarium are involved ( Table 2). Given that samples in the hourly arm were taken 0.8-5.4 h after the last dose, the voriconazole concentration observed in the present study will be less than trough levels seen clinically upon repeated hourly dosing.…”

Prospective Open-Label Study of the Administration of Two-Percent Voriconazole Eye Drops

“…The results from this study are consistent with previous studies (12,16), demonstrating that topically administered voriconazole solutions achieve therapeutic concentration in the aqueous humor for treatment of fungi in Table 1, including those encountered at our institution (RVEEH). Importantly, the concentration resulting from the 2% voriconazole eye drops is not significantly different from that reported for the 1% solution (12).…”

“…In accordance with previous studies (12,16), for an expected standard deviation of Ϯ1.0 mg/liter and a Ϯ0.5-mg/liter margin of error of the mean associated with a 95% confidence level, the required sample size was 13 participants.…”

Stability of extemporaneously prepared voriconazole ophthalmic solution

“…4 A recent study of the use of 1% voriconazole ophthalmic solution as monotherapy in patients undergoing elective eye surgery demonstrated that the concentration of voriconazole in the aqueous humor of the eye was sufficiently high to treat some types of fungal infections but may be inadequate for deep-seated infections that may involve, for example, the vitreous humor of the eye. 16 This finding is similar to that of a recent report by Vemulakonda et al, 17 who studied the penetration of a topically administered 1% voriconazole solution into the eye. The results of these studies suggest that a higher concentration of voriconazole ophthalmic solution (e.g., 2%) may be required to achieve adequate levels of voriconazole in the eye.…”

Penetration of 1% voriconazole eye drops into human vitreous humour: a prospective, open‐label study

“…Accordingly, vitreous clearance of voriconazole seems to be completed within this time interval as no accumulation of voriconazole in the vitreous humour could be detected with this regime (total of 12 doses in this study). This observation may offer a possible answer to the questions raised by Vemulakonda et al 12 about how rapidly topically administered voriconazole is cleared from the eye and how long the levels remain in the therapeutic range following repeated dosing.…”

“…8 These are consistent with results from Hariprasad et al who reported levels of 1.1 Ϯ 0.6 mg/mL in aqueous humour following oral administration (sampled 2.9 Ϯ 0.5 h post dose) 13 , and Vemulakonda et al of 6.49 Ϯ 3.04 mg/mL (sampled 24 Ϯ 14 min post dose) following topical administration. 12 Although this study is limited by the small sample size, the results suggest that hourly application of 1% voriconazole eye drops is likely to produce concentrations that are adequate to treat infections associated with most sensitive Candida species in the posterior chamber, but is of little value when other species such as Aspergillus or Fusarium are involved ( Table 2). Given that samples in the hourly arm were taken 0.8-5.4 h after the last dose, the voriconazole concentration observed in the present study will be less than trough levels seen clinically upon repeated hourly dosing.…”

Prospective Open-Label Study of the Administration of Two-Percent Voriconazole Eye Drops

“…The results from this study are consistent with previous studies (12,16), demonstrating that topically administered voriconazole solutions achieve therapeutic concentration in the aqueous humor for treatment of fungi in Table 1, including those encountered at our institution (RVEEH). Importantly, the concentration resulting from the 2% voriconazole eye drops is not significantly different from that reported for the 1% solution (12).…”

“…In accordance with previous studies (12,16), for an expected standard deviation of Ϯ1.0 mg/liter and a Ϯ0.5-mg/liter margin of error of the mean associated with a 95% confidence level, the required sample size was 13 participants.…”

Stability of extemporaneously prepared voriconazole ophthalmic solution

“…4 A recent study of the use of 1% voriconazole ophthalmic solution as monotherapy in patients undergoing elective eye surgery demonstrated that the concentration of voriconazole in the aqueous humor of the eye was sufficiently high to treat some types of fungal infections but may be inadequate for deep-seated infections that may involve, for example, the vitreous humor of the eye. 16 This finding is similar to that of a recent report by Vemulakonda et al, 17 who studied the penetration of a topically administered 1% voriconazole solution into the eye. The results of these studies suggest that a higher concentration of voriconazole ophthalmic solution (e.g., 2%) may be required to achieve adequate levels of voriconazole in the eye.…”

Penetration of 1% voriconazole eye drops into human vitreous humour: a prospective, open‐label study

“…Accordingly, vitreous clearance of voriconazole seems to be completed within this time interval as no accumulation of voriconazole in the vitreous humour could be detected with this regime (total of 12 doses in this study). This observation may offer a possible answer to the questions raised by Vemulakonda et al 12 about how rapidly topically administered voriconazole is cleared from the eye and how long the levels remain in the therapeutic range following repeated dosing.…”

“…8 These are consistent with results from Hariprasad et al who reported levels of 1.1 Ϯ 0.6 mg/mL in aqueous humour following oral administration (sampled 2.9 Ϯ 0.5 h post dose) 13 , and Vemulakonda et al of 6.49 Ϯ 3.04 mg/mL (sampled 24 Ϯ 14 min post dose) following topical administration. 12 Although this study is limited by the small sample size, the results suggest that hourly application of 1% voriconazole eye drops is likely to produce concentrations that are adequate to treat infections associated with most sensitive Candida species in the posterior chamber, but is of little value when other species such as Aspergillus or Fusarium are involved ( Table 2). Given that samples in the hourly arm were taken 0.8-5.4 h after the last dose, the voriconazole concentration observed in the present study will be less than trough levels seen clinically upon repeated hourly dosing.…”

Prospective Open-Label Study of the Administration of Two-Percent Voriconazole Eye Drops

“…The results from this study are consistent with previous studies (12,16), demonstrating that topically administered voriconazole solutions achieve therapeutic concentration in the aqueous humor for treatment of fungi in Table 1, including those encountered at our institution (RVEEH). Importantly, the concentration resulting from the 2% voriconazole eye drops is not significantly different from that reported for the 1% solution (12).…”

“…In accordance with previous studies (12,16), for an expected standard deviation of Ϯ1.0 mg/liter and a Ϯ0.5-mg/liter margin of error of the mean associated with a 95% confidence level, the required sample size was 13 participants.…”