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document
Lack of a pharmacokinetic interaction between steady-state roflumilast and single-dose midazolam in healthy subjects . AIMS The aim of this study was to investigate the effects of roflumilast , an investigational PDE4 inhibitor for the treatment of COPD and asthma , on the pharmacokinetics of the CYP3A probe drug midazolam and its major metabolites . METHODS In an open , randomized ( for midazolam treatment sequence ) study , 18 healthy male subjects received single doses of midazolam ( 2 mg oral and 1 mg i.v. , 1 day apart ) alone , repeated doses of roflumilast ( 500 microg once daily for 14 days ) alone , and repeated doses of roflumilast together with single doses of midazolam ( 2 mg oral and 1 mg i.v. , 1 day apart ) . RESULTS A comparison of clearance and peak and systemic exposure to midazolam following administration of roflumilast indicated no effect of roflumilast dosed to steady state on the pharmacokinetics of midazolam . Point estimates ( 90 % CI ) were 0.97 ( 0.84 , 1.13 ) for the AUC of i.v . midazolam and 0.98 ( 0.82 , 1.17 ) for that of oral midazolam with and without roflumilast . CONCLUSIONS Therapeutic steady state concentrations of roflumilast and its N-oxide do not alter the disposition of the CYP3A substrate midazolam in healthy subjects . This finding suggests that roflumilast is unlikely to alter the clearance of drugs that are metabolized by CYP3A4 .
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Intervention_Pharmacological
roflumilast
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Intervention_Pharmacological
midazolam
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Intervention_Pharmacological
roflumilast
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Intervention_Pharmacological
midazolam
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Intervention_Pharmacological
midazolam
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Intervention_Pharmacological
midazolam
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Intervention_Pharmacological
roflumilast
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Intervention_Pharmacological
roflumilast together with single doses of midazolam
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Outcome_Physical
pharmacokinetic interaction
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Outcome_Physical
pharmacokinetics of the CYP3A probe
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Outcome_Physical
clearance and peak and systemic exposure
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Outcome_Physical
pharmacokinetics of midazolam .
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Outcome_Physical
disposition of the CYP3A substrate midazolam
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Participant_Condition
healthy
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Participant_Sample-size
18
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Participant_Sex
male
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Participant_Condition
healthy