Is Super Bioavailable Itraconazole better than Conventional Itraconazole?
Due to the 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).
ITZ is a weak base lipophilic
molecule with a limited 55% absolute bioavailability and, for better absorption,
it must be administered with a full meal or cola beverages. Apart from this, it
also possesses many other pharmacokinetic challenges such as inter-individual
and intra-individual variability, reduced absorption in the presence of proton
pump inhibitors, and so on.
TAKE HOME MESSAGE
The current study compares the rate
and extent of serum and sebum concentration of super-bioavailable itraconazole and conventional itraconazole at
different dosing to determine their efficacy and safety in patients with
dermatophytosis.
Super-Bioavailable Itraconazole (SBITZ) was developed to overcome
the pharmacokinetic challenges, providing a more persistent plasma
concentration, minimally altered by gastric acid-suppressive agents and
exhibiting comparable absorption under both fasting and fed conditions.
SBITZ provides improved drug
delivery compared with CITZ.
Due to its non-linear
pharmacokinetic profile, ITZ is commonly prescribed OD. However, in India, it
is commonly prescribed as BD.
Herein, it was found that serum
concentration of SB 130 mg OD, CITZ 200 mg OD and SB 100 mg OD were much higher
than CITZ 100 mg BD.
This indicates that, to achieve better serum concentrations, ITZ should be prescribed as OD dosing.
SB 130 mg OD VS CITZ 100 mg BD
On day 1 only, serum concentrations
of Super-Bioavailable Itraconazole (SBITZ)
130 mg OD were found to be 1.5 times
higher than Conventional ITZ (CITZ) 100 mg BD. Similar findings were
also noted for SB 100 mg OD and CITZ 200 mg OD.
This trend of higher serum concentrations continued until day 28, with SB 130 mg OD having 1.4 times higher serum concentration than the CITZ 100 mg BD.
SB 130 mg OD VS SB 100 mg OD
The result of this study
demonstrated that SB 130 mg OD
achieved 1.28 times higher serum
concentrations than SB 100 mg OD
on day 1 only, which increased until
day 28 where it was 1.16 times higher than SB 100 mg
OD.
In the present study, sebum concentrations of SBITZ 130 mg OD were 1.45, 1.07 and 1.38 times higher than for CITZ 100 mg BD, CITZ 200 mg OD and SBITZ 100 mg OD, respectively, at the end of the study, and this difference was statistically significant compared to CITZ 100 mg BD and SB 100 mg OD.
CONCLUSION
All formulations achieved desired
serum and sebum concentrations required for efficacy in dermatophytosis, but Super-Bioavailable Itraconazole (SBITZ) 130
mg OD and Conventional ITZ (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.
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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.
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