title: The effects of rifampicin on the pharmacokinetics and pharmacodynamics of orally administered nilvadipine to healthy subjects.
abstract: OBJECTIVE
  To study the effects of rifampicin on the pharmacokinetics and pharmacodynamics of nilvadipine.
  
  
  METHODS
  Five healthy adult volunteers received nilvadipine (4 mg) orally before and after a 6 day treatment with rifampicin. Blood and urine were collected and assayed for plasma nilvadipine and urinary 6beta-hydroxycortisol and cortisol.
  
  
  RESULTS
  The treatment with rifampicin reduced the mean (+/- s.d.) AUC of nilvadipine from 17.4 +/- 8.4 to 0.6 +/- 0.4 microg l-1 h (mean difference -16.8 microg l-1 h, 95% CI -9.4, 24.2 microg l-1 h). While the administration of nilvadipine alone elicited a significant (P < 0.05) hypotensive (mean difference for diastolic blood pressure -8 mmHg, 95% CI -4, -12 mmHg) and reflex tachycardia (mean difference 5 beats min-1, 95% CI 1, 9 beats min-1), the treatment with rifampicin abolished these responses. The urinary 6beta-hydroxycortisol/cortisol ratio showed a significant (P < 0.05) increase from 10.3 +/- 4.0 to 50.3 +/- 24.6 by rifampicin: mean difference 40.1, 95% CI 20.4, 59.8.
  
  
  CONCLUSIONS
  Because rifampicin may greatly decrease the oral bioavailability of nilvadipine, caution is needed when these two drugs are to be coadministered.
authors.affiliation: Department of Nephrology, International Medical Center of Japan, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Saima
authors.forename: K
authors.initials: K
authors.lastname: Furuie
authors.forename: H
authors.initials: H
authors.lastname: Yoshimoto
authors.forename: J
authors.initials: J
authors.lastname: Fukuda
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: H
authors.initials: H
authors.lastname: Echizen
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology*
chemical_list: D000904:Antibiotics, Antitubercular; D002121:Calcium Channel Blockers; C035100:nilvadipine; C001380:6 beta-hydroxycortisol; D009543:Nifedipine; D012293:Rifampin; D006854:Hydrocortisone