Efficacy of Super-Bioavailable Itraconazole and Conventional Itraconazole at Different Dosing Regimens in Glabrous Tinea Infection - A Randomized Clinical Trial

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2023 Sep 28

PMID 37766823

Authors

Manjunath M Shenoy

Abhishek De

Bela Shah

Anupam Das

Abir Saraswat

Koushik Lahiri

Sheetal Yadav

Aarti Sarda

Disha Chakraborty

Dharmender J

Shruti Kamat

Yashika Doshi

Nelry Gonsalves

Ankita Choudhary

Dhiraj Dhoot

Namrata Mahadkar

Sumit Bhushan

Rujuta Gadkari

Hanmant Barkate

Affiliations

Soon will be listed here.

Abstract

Introduction: Itraconazole follows non-linear pharmacokinetics and hence is recommended once daily, but in real-world practice, is commonly prescribed as twice daily. Hence, this study aimed to evaluate the efficacy and safety of super-bioavailable-itraconazole-130 mg (SB-130) and conventional-itraconazole-200 mg (CITZ-200) once daily compared with conventional-itraconazole-100 mg (CITZ-100) twice daily in glabrous tinea.

Methods: A total of 261 eligible patients were enrolled in this prospective, randomized, clinical study from December-2021 to August-2022 at seven centers in India. Efficacy and safety assessments were done at week-3 and 6, with follow-up at week-10 for relapse. The primary objective was to assess the proportion of patients who achieved complete cure at week-6 following treatment in all itraconazole groups. The secondary outcomes were safety and clinical and mycological cure rates.

Results: Of 261 patients, 240 were included in the analysis. At week-6, 140 patients were completely cured; thus, overall cure rate was 58.33%. Fifty-five patients (69%) in SB-130 while 47/77 (61%) and 38/83 (46%) patients were completely cured in CITZ-200 and CITZ-100 groups respectively (p<0.05; SB-130: CITZ-100, p=0.32; SB-130: CITZ-200, p=0.058; CITZ-200: CITZ-100). There was no statistical difference in the mycological cure rate and area clearance rate between any of the groups (p=0.14); however, a statistically significant difference was noted for OD dosing over BD dosing in achieving clinical cure rates (p<0.05). A total of 13/140 patients (9%) relapsed following complete cure, with no statistically significant difference between any of the groups (p=0.50). All treatments were safe and well-tolerated, with no discontinuation.

Conclusion: In this clinical study, moderate efficacy with all doses of ITZ was reported but was better with OD dosing. Although there was no statistical difference between SB-130 and CITZ-200, SB-130 may be preferred over CITZ-200 owing to the advantage of SB over the conventional ITZ.

References

Shenoy M, Teerthanath S, Karnaker V, Girisha B, Krishna Prasad M, Pinto J . Comparison of potassium hydroxide mount and mycological culture with histopathologic examination using periodic acid-Schiff staining of the nail clippings in the diagnosis of onychomycosis. Indian J Dermatol Venereol Leprol. 2008; 74(3):226-9. DOI: 10.4103/0378-6323.39584. View

Rengasamy M, Shenoy M, Dogra S, Asokan N, Khurana A, Poojary S . Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) Task Force against Recalcitrant Tinea (ITART) Consensus on the Management of Glabrous Tinea (INTACT). Indian Dermatol Online J. 2020; 11(4):502-519. PMC: 7413465. DOI: 10.4103/idoj.IDOJ_233_20. View

Khurana A, Sardana K, Chowdhary A . Antifungal resistance in dermatophytes: Recent trends and therapeutic implications. Fungal Genet Biol. 2019; 132:103255. DOI: 10.1016/j.fgb.2019.103255. View

De Beule K, van Gestel J . Pharmacology of itraconazole. Drugs. 2001; 61 Suppl 1:27-37. DOI: 10.2165/00003495-200161001-00003. View

Khurana A, Agarwal A, Agrawal D, Panesar S, Ghadlinge M, Sardana K . Effect of Different Itraconazole Dosing Regimens on Cure Rates, Treatment Duration, Safety, and Relapse Rates in Adult Patients With Tinea Corporis/Cruris: A Randomized Clinical Trial. JAMA Dermatol. 2022; . PMC: 9475442. DOI: 10.1001/jamadermatol.2022.3745. View

Lindsay J, Mudge S, Thompson 3rd G . Effects of Food and Omeprazole on a Novel Formulation of Super Bioavailability Itraconazole in Healthy Subjects. Antimicrob Agents Chemother. 2018; 62(12). PMC: 6256753. DOI: 10.1128/AAC.01723-18. View

Cheymol G . Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet. 2000; 39(3):215-31. DOI: 10.2165/00003088-200039030-00004. View

Bae S, Park S, Shim E, Mun J, Kim E, Shin J . Increased oral bioavailability of itraconazole and its active metabolite, 7-hydroxyitraconazole, when coadministered with a vitamin C beverage in healthy participants. J Clin Pharmacol. 2010; 51(3):444-51. DOI: 10.1177/0091270010365557. View

Hanley M, Abernethy D, Greenblatt D . Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010; 49(2):71-87. DOI: 10.2165/11318100-000000000-00000. View

10.

Khurana A, Agarwal A, Singh A, Sardana K, Ghadlinge M, Agrawal D . Predicting a therapeutic cut-off serum level of itraconazole in recalcitrant tinea corporis and cruris-A prospective trial. Mycoses. 2021; 64(12):1480-1488. DOI: 10.1111/myc.13367. View

11.

Singh S, Subba N, Tilak R . Efficacy of Terbinafine and Itraconazole in Different Doses and in Combination in the Treatment of Tinea Infection: A Randomized Controlled Parallel Group Open Labeled Trial with Clinico-Mycological Correlation. Indian J Dermatol. 2020; 65(4):284-289. PMC: 7423219. DOI: 10.4103/ijd.IJD_548_19. View

12.

Nield B, Larsen S, van Hal S . Clinical experience with new formulation SUBA®-itraconazole for prophylaxis in patients undergoing stem cell transplantation or treatment for haematological malignancies. J Antimicrob Chemother. 2019; 74(10):3049-3055. DOI: 10.1093/jac/dkz303. View

13.

Thompson 3rd G, Lewis P, Mudge S, Patterson T, Burnett B . Open-Label Crossover Oral Bioequivalence Pharmacokinetics Comparison for a 3-Day Loading Dose Regimen and 15-Day Steady-State Administration of SUBA-Itraconazole and Conventional Itraconazole Capsules in Healthy Adults. Antimicrob Agents Chemother. 2020; 64(8). PMC: 7526808. DOI: 10.1128/AAC.00400-20. View

14.

Rauseo A, Mazi P, Lewis P, Burnett B, Mudge S, Spec A . Bioavailability of Single-Dose SUBA-Itraconazole Compared to Conventional Itraconazole under Fasted and Fed Conditions. Antimicrob Agents Chemother. 2021; 65(8):e0013421. PMC: 8284459. DOI: 10.1128/AAC.00134-21. View

15.

Sardana K, Khurana A, Singh A, Gautam R . A Pilot Analysis of Morphometric Assessment of Itraconazole Brands Using Dermoscopy and its Relevance in the Current Scenario. Indian Dermatol Online J. 2018; 9(6):426-431. PMC: 6232980. DOI: 10.4103/idoj.IDOJ_339_17. View

16.

Grant S, Clissold S . Itraconazole. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in superficial and systemic mycoses. Drugs. 1989; 37(3):310-44. DOI: 10.2165/00003495-198937030-00003. View

17.

Abuhelwa A, Foster D, Mudge S, Hayes D, Upton R . Population pharmacokinetic modeling of itraconazole and hydroxyitraconazole for oral SUBA-itraconazole and sporanox capsule formulations in healthy subjects in fed and fasted states. Antimicrob Agents Chemother. 2015; 59(9):5681-96. PMC: 4538523. DOI: 10.1128/AAC.00973-15. View

18.

Dhoot D, Kumar Jain G, Manjhi M, Kesharwani P, Mahadkar N, Barkate H . Pharmacokinetic and clinical comparison of super-bioavailable itraconazole and conventional itraconazole at different dosing in dermatophytosis. Drugs Context. 2023; 12. PMC: 9835899. DOI: 10.7573/dic.2022-8-1. View

19.

Zimmermann T, Yeates R, Albrecht M, Laufen H, Wildfeuer A . Influence of concomitant food intake on the gastrointestinal absorption of fluconazole and itraconazole in Japanese subjects. Int J Clin Pharmacol Res. 1994; 14(3):87-93. View

20.

Hardin T, Graybill J, Fetchick R, Woestenborghs R, Rinaldi M, Kuhn J . Pharmacokinetics of itraconazole following oral administration to normal volunteers. Antimicrob Agents Chemother. 1988; 32(9):1310-3. PMC: 175857. DOI: 10.1128/AAC.32.9.1310. View