Serum and sebum pharmacokinetics evaluation of a novel formulation of itraconazole in healthy volunteers

Dhoot, Dhiraj; Mahajan, Harshal; Jain, Girish Kumar; Deshmukh, Gajanan Rajpal; Barkate, HanmantV

doi:10.4103/ijdd.ijdd_23_21

Cited by 2 publications

(5 citation statements)

References 23 publications

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“…Sobue et al noted that the extent of itraconazole binding to skin keratin was 94-97%, which was several times higher compared to fluconazole and griseofulvin [16]. Owing to its lipophilicity and high volume of distribution, itraconazole is distributed into the skin in higher quantities than its plasma concentration [6].…”

Section: Discussionmentioning

confidence: 99%

“…As reported previously, the concentration of SB-ITZ in plasma and tissue samples was determined by Highperformance liquid chromatography (HPLC) [6]. Briefly, HPLC (LC-10 AT VP, Shimadzu Corp., Kyoto, Japan) coupled with UV-Vis Detector (SPD-10A VP, Shimadzu Corp., Kyoto, Japan) was used to determine ITZ.…”

Section: Concentration Analysis Methodsmentioning

confidence: 99%

“…Many risk factors have been identified for this change, and obesity has been regarded as one of the important risk factors [1][2][3][4][5]. Owing to these changes, the current management of dermatophytosis has evolved as combination therapy, including topical and systemic antifungals and itraconazole, the most commonly prescribed systemic antifungal drug [6]. However, due to pharmacokinetic obstacles like food dependency, a requirement of an acidic environment for optimal absorption, etc., presented by conventional formulation of itraconazole, a newer itraconazole formulation, super-bioavailable itraconazole (SB-ITZ) was recently approved by Central Drugs Standard Control Organization (CDSCO) in India [7,8].…”

Section: Introductionmentioning

confidence: 99%

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The Optimal Dosing Regimen of Super Bioavailable Itraconazole in Obesity: An Experimental Rat Model Study

Jain¹,

Chitnis²,

Singhal³

et al. 2023

Cureus

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BackgroundObesity may alter tissue distribution and clearance of several drugs, especially lipophilic ones. Itraconazole, a lipophilic drug, has been recently introduced in a super-bioavailable formulation (SB-ITZ) for the treatment of dermatophytosis. Evidence regarding optimal dosing of SB-ITZ in obesity is lacking. A current experimental study was planned to analyze tissue concentrations of SB-ITZ at different doses in obese and non-obese rats. Materials and methodsThirty-six Wistar albino rats of either sex were divided into obese and non-obese rats equally. Further, rats in both categories were divided into three dosing groups. Group 1 received SB-ITZ 13 mg once daily in the morning, group 2 received SB-ITZ 13 mg in the morning and 6.5 mg in the evening, while Group 3 rats received SB-ITZ 13 mg twice daily, orally. Concentrations of SB-ITZ in the skin, serum, and fatty tissue were assessed in each group on days 7, 14, 21, and 28. Comparison of SB-ITZ concentrations in various tissues in obese and non-obese rats and inter-group comparison of tissue concentrations across the three dosing regimens was done at day 28 and expressed as Mean ± SD.36 Wistar rats were divided into obese and nonobese rats equally. ResultsAt day 28, skin concentrations of SB-ITZ were 5.36±1.1, 8.9±1.7 and 10.13±1.7 µg/g in Groups 1, 2, and 3, respectively, in non-obese rats, which was statistically significant (p<0.05) than skin concentration of obese rats (2.72±0.6, 4.2±0.7 and 4.66±0.5 µg/g) for the corresponding dosing groups respectively. Skin concentration of SB-ITZ was statistically significant for Groups 2 and 3 as compared to Group 1. Still, no statistically significant difference was noted between Groups 2 and 3 in non-obese and obese rats. Fatty tissue concentration of SB-ITZ was comparable in all 3 dosing regimens in non-obese and obese rats. But on the intergroup comparison, a statistically significant difference was observed for Groups 2 and 3 against Group 1 (p<0.05). Increasing the dose of SB-ITZ increased serum concentration. In non-obese rats, a statistically significant difference was noted between Group 2 (74.33±6.6 ng/ml) and Group 1 (52.5±9.9 ng/ml); p<0.01 and also in Group 3 (81.33±6.8 ng/ml) against Group 1; p<0.01. Group 3 achieved significantly higher concentration than the other two groups in obese rats (Group 3; 72±5.3, Group 2; 60.5±4.3, and Group 1; 45±7 ng/ml; p<0.01). ConclusionOverall, skin, fatty tissue, and serum concentrations of SB-ITZ were higher in non-obese rats compared to obese rats in all three dosing groups. Moreover, skin and fatty tissue concentrations were proportionately higher than serum in all the groups in non-obese and obese rats. Though the skin concentration of nonobese rats was significantly higher than obese rats, skin concentration in obese rats was within the minimum inhibitory concentration (MIC) range, demonstrating the efficacy of all dosing regimens.

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Section: Discussionmentioning

confidence: 99%

Section: Concentration Analysis Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Optimal Dosing Regimen of Super Bioavailable Itraconazole in Obesity: An Experimental Rat Model Study

Jain¹,

Chitnis²,

Singhal³

et al. 2023

Cureus

Self Cite

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“…The other advantage of a higher strength is the increased effectiveness of the treatment in infections that affect the hair follicles (Tinea capitis) [35]. A study comparing the pharmacokinetics of SB ITZ and CITZ demonstrated that SB ITZ usage leads to higher sebum concentrations of ITZ [36].…”

Section: Naïve Dermatophytosismentioning

confidence: 99%

“…Furthermore, as it is weakly basic, it requires an acidic environment for dissolution. Therefore, PPIs that lower gastric acidity also reduce the absorption and bioavailability of CITZ by 66% [32,36]. In contrast, SB ITZ is available in a pH-dependent matrix with intestinal absorption, has better bioavailability, and is not influenced by gastric pH [32].…”

Section: Use Of Sb Itz In Patients With Comorbiditiesmentioning

confidence: 99%

Clinical Use of Super-Bioavailable Itraconazole for the Management of Dermatophytosis: Consensus Statement by Dermatologists from India via the Modified Delphi Technique

Saraswat,

Dogra,

Shenoy

et al. 2024

Dermatology

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Introduction: Super bioavailable itraconazole (SB ITZ) overcomes the limitations of conventional itraconazole (CITZ) such as inter-individual variability and reduced bioavailability. It has been approved for systemic mycoses in Australia and Europe as 50mg and the United States as 65mg and in India as 50mg, 65mg, 100mg, and 130mg. However, data on the ideal dose and duration of SB ITZ treatment in managing dermatophytosis is insufficient. This consensus discusses the suitability, dosage, duration of treatment, and relevance of using SB ITZ in managing dermatophytosis in different clinical scenarios. Methods: Sixteen dermatologists, (>15 years of experience in the field and ≥2 years clinical experience with SB ITZ) formed the expert panel. A modified Delphi technique was employed, and a consensus was reached if the concordance in response was >75%. Results: A total of 26 consensus statements were developed. The preferred dose of SB ITZ is 130mg once daily and if not tolerated, 65mg twice daily. The preferred duration for treating naïve dermatophytosis is 4–6 weeks and that for recalcitrant dermatophytosis is 6–8 weeks. Moreover, cure rates for dermatophytosis are a little better with SB ITZ than with CITZ with a similar safety profile as of CITZ. Better patient compliance and efficacy are associated with SB ITZ than with CITZ, even in patients with comorbidities and special needs such as patients with diabetes, extensive lesions, corticosteroid abuse, adolescents, and those on multiple drugs. Conclusion: Expert opinions indicate that overall clinical experience with SB ITZ is better than that with CITZ.

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Serum and sebum pharmacokinetics evaluation of a novel formulation of itraconazole in healthy volunteers

Cited by 2 publications

References 23 publications

The Optimal Dosing Regimen of Super Bioavailable Itraconazole in Obesity: An Experimental Rat Model Study

The Optimal Dosing Regimen of Super Bioavailable Itraconazole in Obesity: An Experimental Rat Model Study

Clinical Use of Super-Bioavailable Itraconazole for the Management of Dermatophytosis: Consensus Statement by Dermatologists from India via the Modified Delphi Technique

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