The effects of rifampicin on the pharmacokinetics and pharmacodynamics of orally administered nilvadipine to healthy subjects.
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.
Saima
S
S
Department of Nephrology, International Medical Center of Japan, Tokyo, Japan.
Furuie
K
K
Yoshimoto
H
H
Fukuda
J
J
Hayashi
T
T
Echizen
H
H
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*
D000904:Antibiotics, Antitubercular; D002121:Calcium Channel Blockers; C035100:nilvadipine; C001380:6 beta-hydroxycortisol; D009543:Nifedipine; D012293:Rifampin; D006854:Hydrocortisone