Effect of rifampin, an inducer of CYP3A and P-glycoprotein, on the pharmacokinetics of risperidone.
The authors studied the effect of rifampin, a dual inducer of CYP3A and P-glycoprotein, on the pharmacokinetics and pharmacodynamics of risperidone in humans. Ten healthy male subjects were treated daily for 7 days with 600 mg rifampin or with placebo. On day 6, a single dose of 1 mg risperidone was administered. Plasma risperidone and 9-hydroxyrisperidone concentrations were measured. Rifampin significantly decreased the mean area under the plasma concentration-time curve by 51% for risperidone, by 43% for 9-hydroxyrisperidone, and by 45% for the active moieties (risperidone + 9-hydroxyrisperidone). Rifampin also decreased the peak plasma concentration of risperidone by 38%, 9-hydroxyrisperidone by 46%, and the active moieties by 41%. The apparent oral clearance of risperidone approximately doubled after rifampin treatment. Thus, rifampin reduced the exposure to risperidone, probably because of a decrease in its bioavailability through the induction of CYP3A and probably P-glycoprotein.
Kim
Kyoung-Ah
KA
Department of Clinical Pharmacology & Toxicology, Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Sungbuk-gu, Seoul 136-705, Korea.
Park
Pil-Whan
PW
Liu
Kwang-Hyeon
KH
Kim
Kwon-Bok
KB
Lee
Heon-Jeong
HJ
Shin
Jae-Gook
JG
Park
Ji-Young
JY
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000284:Administration, Oral; D000328:Adult; D000483:Alleles; D019540:Area Under Curve; D018592:Cross-Over Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D005838:Genotype; D006207:Half-Life; D006801:Humans; D007555:Isoxazoles / Q000097:blood / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D000068882:Paliperidone Palmitate; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011743:Pyrimidines / Q000097:blood / Q000378:metabolism; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology*; D018967:Risperidone / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D013997:Time Factors
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007555:Isoxazoles; D011743:Pyrimidines; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D018967:Risperidone; D000068882:Paliperidone Palmitate; D012293:Rifampin