International Journal of Research in Dermatology | January-February 2023 | Vol 9 | Issue 1 Page 59 International Journal of Research in Dermatology Dhoot DS et al. Int J Res Dermatol. 2023 Jan;9(1):59-60 http://www.ijord.com Letter to the Editor Comparative analysis of serum and sebum concentration of super- bioavailable itraconazole 50 versus 65 mg in healthy adult volunteers Sir, Super-bioavailable itraconazole (SBITZ) is a new form of itraconazole which overcomes the pharmacokinetic issues of conventional itraconazole (CITZ). Currently two strengths are approved globally for SBITZ; 50 mg and 65 mg which exhibit greater bioavailability than CITZ and widely prescribed in systemic mycosis and dermatophytosis. 1 Though both the strengths have proven to be bioequivalent with CITZ 100 mg but difference was reported in achieving therapeutic concentration of ITZ in patients. 2,3 Secondly, skin kinetics study in terms of sebum concentration is lacking for both the strengths. Since SBITZ is commonly prescribed in dermatophytosis in India, assessment of sebum levels plays important role for treatment outcome which is correlated with serum levels (trough concentration) of ITZ. Hence, current study was planned to evaluate the serum and sebum concentration achieved by both strengths in Indian healthy adult volunteers. After independent ethics committee approval, twenty healthy volunteers were enrolled and divided equally into 2 groups with duration of study being 14 days. Group I received SBITZ 65 mg (SB 65) twice daily while group II received SBITZ 50 mg (SB 50) twice daily after food. Trough concentration was evaluated on day 1, 3, 7 and 14 while sebum concentration was evaluated on day 7 and day 14. Serum concentration was analyzed by high performance liquid chromatography (HPLC) method by inserting IV catheter into forearm vein. 4 Sebum concentration was analyzed by paper absorption method wherein pre-weighed rolling flax paper (OCB, France) was held over the demarcated area on forehead for 3 hours and post-test, the paper was weighed again to determine the quantity of the sebum. 5 For both the strengths, serum concentration was found to increase gradually from day 1 onwards till day 14. But trough concentration of day 7 and 14 were considered for analysis as itraconazole had shown to achieve steady state concentration as early as 7 days. 6 SB 65 was found to be statistically significant than SB 50 in achieving trough concentration at day 14 as shown in Table 1. Similarly, sebum concentration was also statistically significant (p<0.05) for SB 65 against SB 50 on both days (Table 1). In SB 50 group, 3 volunteers failed to achieve therapeutic concentration of ITZ (>1000 ng/ml) as compared to one patient in SB 65 group at end of 14 days. Table 1: Trough concentration and sebum concentration of SB 50 and SB 65 at day 7 and 14. Subject no. Trough concentration of ITZ (ng/ml) Sebum concentration of ITZ (ng/mg) Day 7 Day 14 P value Day 7 Day 14 P value SB 50 SB 65 SB 50 SB 65 SB 50 SB 65 SB 50 SB 65 1 1215 1245 1470 1475 <0.05* 970 1080 975 1220 <0.05# 2 1150 1268 1280 1390 1010 1010 1230 1140 3 1340 1590 1390 1730 880 1160 945 1320 4 1380 1370 1460 1468 800 1095 1008 1210 5 920 1396 960 1475 950 1050 1050 1100 6 1430 1400 1470 1590 970 1120 1089 1110 7 1213 957 1350 980 1118 920 1145 965 8 965 1410 970 1600 850 1100 960 1268 9 1280 1380 1320 1493 1022 1008 980 1170 10 960 1395 990 1570 1045 990 1050 1098 *Statistical significant at day 14 only, #statistical significant at day 7 and 14. In the current scenario for management of dermatophytosis in India, ITZ remains a useful antifungal agent, along with topical treatment, but its usefulness is hindered by its inherent pharmacokinetic shortcomings, leading to inconsistent therapeutic concentrations. A newer formulation of SBITZ has shown more reliable attainment of therapeutic concentration compared with older formulations of CITZ and is approved by drugs controller general of India (DCGI) in invasive mycosis in the strength of 50 and 65 mg. The availability of two strengths had created some dilemma at physicians’ level regarding prescription and hence this study was performed to evaluate trough concentration and correlate with sebum concentration for both strengths. DOI: https://dx.doi.org/10.18203/issn.2455-4529.IntJResDermatol20223279