6439
document
In vivo effect of clarithromycin on multiple cytochrome P450s . The in vivo effects of oral clarithromycin administration on the in vivo activity of cytochrome P450 1A2 , 2C9 , and 2D6 were determined . The cytochrome P450 probes caffeine ( CYP1A2 ) , tolbutamide ( CYP2C9 ) , and dextromethorphan ( CYP2D6 ) were administered as an oral cocktail prior to and 7 days after oral clarithromycin ( 500 mg twice daily ) administration to 12 healthy male subjects . Blood and urine samples were collected and assayed for each of the compounds and their metabolites using high-performance liquid chromatography . The CYP1A2 indices , oral caffeine clearance ( 6.2 +/- 3.3 l/h before and 5.7 +/- 4.2 l/h after , p > 0.05 ) and the 6-h paraxanthine to caffeine serum concentration ratio ( 0.49 +/- 0.3 before and 0.44 +/- 0.3 after , p > 0.05 ) , were unchanged following clarithromycin dosing . Neither the tolbutamide oral clearance ( 0.77 +/- 0.28 l/h before and 0.72 +/-0.24 l/h after , p > 0.05 ) nor the tolbutamide urinary metabolic ratio ( 779 +/- 294 before and 681 +/- 416 after , p > 0.05 ) indices of CYP2C9 were altered by clarithromycin administration . In the case of CYP2D6 , the dextromethorphan to dextrorphan urinary ratio was not significantly different before ( 0.021 +/- 0.04 ) and after ( 0.024 +/- 0.06 ) clarithromycin dosing . In conclusion , clarithromycin does not appear to alter the in vivo catalytic activity of CYP1A2 , CYP2C9 , and CYP2D6 in healthy individuals as assessed by caffeine , tolbutamide , and dextromethorphan , respectively .
6440
Intervention_Pharmacological
clarithromycin
6441
Intervention_Pharmacological
clarithromycin
6442
Intervention_Pharmacological
caffeine
6443
Intervention_Pharmacological
tolbutamide
6444
Intervention_Pharmacological
dextromethorphan
6445
Intervention_Pharmacological
clarithromycin
6446
Intervention_Pharmacological
tolbutamide
6447
Intervention_Pharmacological
tolbutamide
6448
Intervention_Pharmacological
clarithromycin
6449
Intervention_Pharmacological
dextromethorphan
6450
Intervention_Pharmacological
clarithromycin
6451
Intervention_Pharmacological
clarithromycin
6452
Outcome_Physical
Blood and urine samples
6453
Outcome_Physical
CYP1A2 indices
6454
Outcome_Physical
oral caffeine clearance
6455
Outcome_Physical
6-h paraxanthine to caffeine serum concentration ratio
6456
Outcome_Physical
tolbutamide oral clearance
6457
Outcome_Physical
tolbutamide urinary metabolic ratio
6458
Outcome_Physical
dextromethorphan
6459
Outcome_Physical
dextrorphan urinary ratio
6460
Outcome_Other
significantly different
6461
Outcome_Physical
vivo catalytic activity
6462
Participant_Sample-size
12
6463
Participant_Condition
healthy
6464
Participant_Sex
male