Association between major Multidrug Resistance 1 (MDR1) gene polymorphisms and plasma concentration of prolactin during risperidone treatment in schizophrenic patients.
An in vitro study has suggested that risperidone is a substrate of P-glycoprotein, which is coded by MDR1gene. The rate of P-glycoprotein efflux transport can mediate brain penetration of lipophilic drugs. We therefore studied the effects of major polymorphisms of MDR1 gene on plasma concentrations of prolactin. Subjects included 175 schizophrenic patients (68 males, 107 females) who were receiving 3 mg of risperidone twice daily for at least 4 weeks. Sample collections were conducted 12 h after the bedtime dosing. The plasma concentrations of prolactin in females were significantly higher than in males (54.3+/-27.2 versus 126.8+/-70.2 ng/ml, p<0.001). There was no difference in mean (+/-SD) plasma concentration of prolactin between C3435T genotypes [C/C, C/T, T/T; 62.3+/-33.3, 49.4+/-15.6, 53.2+/-33.2 ng/ml, ns] or G2677T/A genotypes [G/G, G/T or A, T or A/T or A; 58.0+/-27.7, 58.5+/-35.0, 46.1+/-20.7 ng/ml, ns] in males nor between C3435T genotypes (123.6+/-65.0, 127.8+/-79.2, 130.4+/-49.7 ng/ml, ns) or G2677T/A genotypes (123.3+/-67.0, 97.7+/-71.2, 144.9+/-69.9 ng/ml, ns) in females. Multiple regression analyses including plasma drug concentration and age revealed that plasma concentration of prolactin correlated with gender (standardized beta=0.540, p<0.001) and negatively with age (standardized beta=-0.183, p<0.01). No correlations were found between prolactin concentration and MDR1 genotypes. These findings suggest that prolactin concentrations in females are much higher than in males but the major MDR1 variants are not associated with the plasma concentration of prolactin.
Yasui-Furukori
Norio
N
Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan. yasufuru@cc.hirosaki-u.ac.jp
Tsuchimine
Shoko
S
Saito
Manabu
M
Nakagami
Taku
T
Sato
Yasushi
Y
Kaneko
Sunao
S
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002853:Chromatography, Liquid / Q000379:methods; D004334:Drug Administration Schedule; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011388:Prolactin / Q000097:blood*; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D012737:Sex Factors
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014150:Antipsychotic Agents; D011388:Prolactin; D018967:Risperidone