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A pilot study to assess simultaneous administration of oral midazolam (MDZ) and fexofenadine (FEX) for the evaluation of cytochrome (CYP) 3A4 and P‐glycoprotein (P‐GP) activities
Author(s) -
Garrett M.,
Smeraglia J.,
Lin X.,
Tan L.,
Tran J.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.065
Subject(s) - cyp3a4 , pharmacokinetics , pharmacology , fexofenadine , midazolam , cyp2d6 , chemistry , in vivo , drug interaction , analysis of variance , cmax , pharmacodynamics , medicine , cytochrome p450 , biochemistry , metabolism , biology , microbiology and biotechnology , sedation
Background Many drug interactions may involve both CYP3A4 and P‐gp. Such interactions reflect overlapping substrate specificities and modulators between CYP3A4 and P‐gp. MDZ and FEX are ideal in vivo probe substrates for the assessment of CYP3A4 and P‐gp mediated interactions, respectively. It is desirable to evaluate the effect of an investigational drug on CYP3A4 and P‐gp activities by administering these 2 probe substrates simultaneously. This pilot study was conducted to evaluate the potential interaction between these two probe substrates. Method Fifteen healthy subjects were randomized to receive the following single‐dose regimens separated by a 7‐day washout: A) oral MDZ 7.5 mg; B) FEX 120 mg; and C) oral MDZ 7.5 mg+ FEX 120 mg. Blood samples were collected for pharmacokinetic (PK) assessments. PK parameters were estimated by standard non‐compartmental methods using WinNonlin. Statistical analyses were performed using ANOVA with α= 0.05. Results No significant differences in drug exposure were observed when MDZ or FEX was given alone and in combination. Preliminary results are shown below. (see Table) Conclusion Results from this pilot study suggest no significant interaction between oral MDZ and FEX. Clinical Pharmacology & Therapeutics (2005) 77 , P45–P45; doi: 10.1016/j.clpt.2004.12.065AUC ∞ (h· ng/mL) Mean± SDProbe Alone Combination P‐valueMDZ 110 ± 33 118 ± 34 0.156 FEX 2020 ± 576 1870 ± 930 0.510