Rifampin, a cytochrome P450 3A inducer, decreases plasma concentrations of antipsychotic risperidone in healthy volunteers.
BACKGROUND
Although cytochrome P450 (CYP) 2D6 is often thought to be the only CYP responsible for the metabolism of risperidone, many reports suggest that CYP3A may be involved too. Rifampin, a potent CYP3A inducer, has been known to markedly decrease plasma concentrations of various drugs, which are concomitantly administered during treatment.


OBJECTIVE
To examine the effect of rifampin on plasma concentrations of a single oral dose of risperidone in healthy Thai male volunteers.


METHODS
In an open, randomized two-phase crossover study, separated by a 2-week period, 10 healthy Thai male volunteers received a single oral dose of 4-mg risperidone alone or with 600 mg rifampin, orally once daily for 5 days. Serial blood samples were collected at specific time points for a 48-h period. Risperidone was measured in plasma using high performance liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined by using non-compartmental analysis.


RESULTS
Co-administration with 600-mg rifampin once daily for 5 days was associated with a significant decrease in risperidone area under the curve (AUC(0-48)) and maximal concentration (C(max)) by 72% (157 x 49 +/- 48 x 80 vs. 42 x 66 +/- 7 x 81 ng/L/h; P<0 x 01) and 50% (32 x 44 +/- 6 x 05 vs. 16 x 16 +/- 2 x 73 ng/mL; P<0 x 05), respectively when compared with risperidone alone.


CONCLUSIONS
Rifampin when used concurrently with risperidone significantly decreases the plasma concentration of risperidone. Our results provide in vivo evidence of the involvement of CYP3A in the metabolism of risperidone, in addition to CYP2D6. Thus, co-administration of risperidone with CYP3A inducer(s), including rifampin should be recognized or avoided in clinical practice.
Mahatthanatrakul
W
W
Department of Pharmacology, Faculty of Science, Prince of Songkla University, Hat Yai, Thailand.
Nontaput
T
T
Ridtitid
W
W
Wongnawa
M
M
Sunbhanich
M
M
D000284:Administration, Oral; D000328:Adult; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004244:Dizziness / Q000139:chemically induced; D004347:Drug Interactions; D006207:Half-Life; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D015508:Nasal Obstruction / Q000139:chemically induced; D012293:Rifampin / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D018967:Risperidone / Q000097:blood / Q000493:pharmacokinetics*; D013056:Spectrophotometry, Ultraviolet; D013607:Tablets; D013997:Time Factors
D000904:Antibiotics, Antitubercular; D014150:Antipsychotic Agents; D002214:Capsules; D013607:Tablets; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D018967:Risperidone; D012293:Rifampin