Predicting a therapeutic cut‐off serum level of itraconazole in recalcitrant tinea corporis and cruris—A prospective trial

Khurana, Ananta; Agarwal, Aastha; Singh, Ashutosh; Sardana, Kabir; Ghadlinge, Manik; Agrawal, Diksha; Panesar, Sanjeet; Sethia, Khushboo; Chowdhary, Anuradha

doi:10.1111/myc.13367

Cited by 26 publications

(26 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, oral formulations of ITC have erratic absorption patterns leading to wide fluctuations in its serum concentrations. Although, monitoring of serum levels of ITC as in systemic mycoses is important for effective treatment outcome [ 41 , 42 ]. However, the high cost burden associated with regular therapeutic drug monitoring for this extremely prevalent infection, especially in lower-middle countries, is not practical.…”

Section: Multidrug-resistant T Indotine...mentioning

confidence: 99%

The emergence and worldwide spread of the species Trichophyton indotineae causing difficult-to-treat dermatophytosis: A new challenge in the management of dermatophytosis

et al. 2022

Self Cite

View full text Add to dashboard Cite

Section: Multidrug-resistant T Indotine...mentioning

confidence: 99%

The emergence and worldwide spread of the species Trichophyton indotineae causing difficult-to-treat dermatophytosis: A new challenge in the management of dermatophytosis

et al. 2022

Self Cite

View full text Add to dashboard Cite

“… 21 – 26 However, Khurana et al indicated a cut-off value of serum concentration of 200 ng/mL in dermatophytosis. 27 Although toxicity levels of plasma ITZ are challenging to assess, some studies indicated that C trough levels between 2,000 and 5000 ng/mL are suggestive of increased side-effect profiles. 28 , 29 In present study, C trough levels from day 1 onwards were never above 2000 ng/mL in any of the groups, indicating safety even at high OD dosing.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and clinical comparison of super-bioavailable itraconazole and conventional itraconazole at different dosing in dermatophytosis

Dhoot¹,

Jain²,

Manjhi³

et al. 2023

DIC

View full text Add to dashboard Cite

Background Due to changing face of dermatophytosis in India, many dermatologists practice different dosing patterns of itraconazole (ITZ). Recently, a new form of ITZ, super-bioavailable ITZ (SBITZ), has been commercialized to overcome the pharmacokinetic challenges of conventional ITZ (CITZ). Serum and sebum concentration of ITZ plays an important role in the management of dermatophytosis. Hence, the current study compares the rate and extent of serum and sebum concentration of SBITZ and CITZ at different dosing to determine their efficacy and safety in patients with dermatophytosis. Methods This was an open-label, randomized, four-arm study including 40 adult patients diagnosed with glabrous tinea who were randomized equally into four groups to receive either CITZ-100-BD or CITZ-200-OD (2×100 mg capsules) or SBITZ-130-OD or SBITZ-100-OD (2×SBITZ-50 mg capsules) for 4 weeks. Serum and sebum samples were analysed at different time intervals along with clinical efficacy and safety. Results For serum concentration, on day 28, the arithmetic mean and standard deviation (SD) for CITZ-100-BD, CITZ-200-OD, SB-130-OD and SB100-OD were 1262±233.5 ng/mL, 1704±261.6 ng/mL, 1770±268.9 ng/mL and 1520±231.7 ng/mL, respectively, which was statistically significant for OD dosing of ITZ/SBITZ over CITZ-100-BD. Similarly, for sebum concentration, the arithmetic mean and SD for CITZ-100-BD, CITZ-200-OD, SB-130-OD and SB-100-OD were 1042±163.45 ng/mg, 1423±192.46 ng/mg, 1534±227.55 ng/mg and 1107±182.35 ng/mg, respectively, which was statistically significant for SB-130-OD and CITZ-200-OD over CITZ-100-BD and SBITZ-100-OD dosing. No significant difference was noted between SBITZ-130 and CITZ-200 ( p =0.25). Only two patients achieved complete cure in the SBITZ-130 group, whereas no patients achieved the same in other groups ( p =0.47). All the dosages were very well tolerated with only 12 adverse events reported by ten patients in all groups. Conclusion All formulations achieved desired serum and sebum concentrations required for efficacy in dermatophytosis, but SB 130 mg OD and CITZ 200 mg OD were statistically significant than other ITZ doses in achieving sebum concentration. Additionally, SBITZ 130 mg OD was bioequivalent to CITZ 200 mg OD and achieved similar results to those of CITZ 200 mg OD but at 35% lower drug concentrations.

show abstract

“…This observed increase in frequency and severity has been attributed to many factors including the widespread use of high-potency steroids in topical formulations and misuse of antifungal agents. Host-related factors, abnormal drug pharmacokinetics (PK) [ 7 , 8 ], and differences in bioavailability among many itraconazole formulations available in India [ 9 ], have been considered among the factors for treatment failures. To date, there is no clear evidence that supports these observations.…”

Section: Introductionmentioning

confidence: 99%

No evidence of resistance to itraconazole in a prospective real-world trial of dermatomycosis in India

et al. 2023

View full text Add to dashboard Cite

Background The prevalence of superficial fungal infections in India is believed to have increased substantially in the past decade. We evaluated the treatment outcomes and risk factors associated with clinical response to a treatment course of itraconazole for the management of dermatomycosis in India. Methods In this real-world, prospective pilot study (August 2019 to March 2020), adult participants (18–60 years), diagnosed with T. cruris or T. corporis, received itraconazole 200 mg/day (any formulation) orally for 7 days, and were followed for an additional 7 days. Results The study was terminated early due to the COVID-19 pandemic. Of 40 enrolled participants (mean [SD] age, 35.5 [12.73] years; {62.5%}] male; 37 received itraconazole and 20 (50%) completed the study. The median (range) Clinical Evaluation Tool Signs and Symptoms total score at baseline was 5.5 (2–10). Clinical response of “healed” or “markedly improved” based on the Investigator Global Evaluation Tool at day 7 (primary objective) was 42.9% (12/28; 95% CI: 24.53%, 61.19%). Itraconazole minimum inhibitory concentration for identified microorganisms, T. mentagrophytes species complex (91.7%) and T. rubrum (8.3%), was within the susceptibility range (0.015–0.25 mcg/mL). At day 14, 8/13 (61.5%) participants achieved a mycological response, 2/13 participants (15.4%) had a mycological failure and 90% showed a clinical response. Conclusion COVID-19 pandemic affected patient recruitment and follow-up, so the findings call for a careful interpretation. Nevertheless, this real-world study reconfirmed the clinical efficacy and microbial susceptibility to itraconazole for the fungi causing dermatophytosis in India. Trial registration Trial registration number: Clinicaltrials.gov NCT03923010.

show abstract

Predicting a therapeutic cut‐off serum level of itraconazole in recalcitrant tinea corporis and cruris—A prospective trial

Cited by 26 publications

References 32 publications

The emergence and worldwide spread of the species Trichophyton indotineae causing difficult-to-treat dermatophytosis: A new challenge in the management of dermatophytosis

The emergence and worldwide spread of the species Trichophyton indotineae causing difficult-to-treat dermatophytosis: A new challenge in the management of dermatophytosis

Pharmacokinetic and clinical comparison of super-bioavailable itraconazole and conventional itraconazole at different dosing in dermatophytosis

No evidence of resistance to itraconazole in a prospective real-world trial of dermatomycosis in India

Contact Info

Product

Resources

About