Pharmacokinetics/Pharmacodynamics study of Fixtral SB as compared to supra bioavailable itraconazole and conventional itraconazole  

作　　者：Syed Mujtaba Hussain Naqvi Monil Yogesh Neena Gala Snehal Muchhala Anand Arumugam Dhananjay Panigrahi Dipak Patil Rahul Rathod Amey Mane 

机构地区：[1]Medical Affairs,Dr Reddy’s Laboratories,Hyderabad 500016,India [2]Global Clinical Management,Dr Reddy’s Laboratories,Hyderabad 500016,India [3]Formulation Development,Dr Reddy’s Laboratories,Hyderabad 500016,India

出　　处：《World Journal of Pharmacology》2023年第1期1-11,共11页世界药理学杂志

摘　　要：BACKGROUND Itraconazole is a broad-spectrum triazole antifungal inhibiting fungal growth by inhibiting ergosterol synthesis and exhibits a nonlinear pharmacokinetic profile.Erratic absorption pattern with wide fluctuations in blood levels causes inconsistent and unpredictable clinical behaviour of this drug despite its low minimum inhibitory concentration(MIC)as compared to other antifungal agents.AIM To compare the oral bioavailability and bioequivalence of Fixtral SB(supra bioavailable itraconazole)with reference product R2(supra bioavailable 2×50 mg itraconazole).METHODS The study population consisted of 54 healthy volunteers,aged between 18-45 years and randomized to receive a single oral dose of either test[T;Fixtral SB(supra bioavailable itraconazole)100 mg]or reference product(R1;Sporanox 100 mg×2 capsules and R2;Lozanoc capsules 50 mg×2 capsules).Blood samples were taken pre-dose and post-dose up to 96 h.The study evaluated bioequivalence by comparing the oral bioavailability of the test product with reference product R2.The pharmacodynamic characteristics of the drug were evaluated by comparing the test product with reference product R1.Pharmacokinetics(PK)-PD comparative analysis[area under the concentration-time curve(AUC)/minimum inhibitory concentration(MIC)>25]was performed for conventional itraconazole 100 mg and supra bioavailable itraconazole 50 mg.Adverse events(AEs)assessments were performed in each study period and post-study evaluation.RESULTS Statistical analysis of primary PK variables revealed bioequivalence,with confidence intervals being completely inside the acceptance criteria of 80%-125%.The peak concentration levels of itraconazole were achieved at 10 h(T)and 8.5 h(R2),respectively.Pharmacodynamic parameter assessment showed that AUC/MIC for R1 are comparable to Fixtral SB 100mg for MIC levels up to 16mcg/mL(P>0.05 and observed P=0.3196).Six AEs were observed that were mild to moderate in severity and resolved.No severe AE was reported.CONCLUSION Test product itraconazole Capsule

关 键 词：Supra-Bioavailable itraconazole Conventional itraconazole Oral bioavailability PHARMACODYNAMICS EFFICACY Adverse events 

分 类 号：O62[理学—有机化学]