MDR1 genotype-related duodenal absorption rate of digoxin in healthy Japanese subjects.
OBJECTIVE
Recent clinical studies suggest the importance of the MDR1 genotype at position 3435 (C3435T) in terms of pharmacokinetics, but there is still no consensus in reports on the relationship between the genotype and plasma/serum concentration-time profiles of drugs after conventional oral administration. This study was performed to elucidate the effects of C3435T on the rate of duodenal absorption of digoxin in healthy Japanese subjects.


METHODS
Digoxin solution was sprinkled directly over the surface of the duodenum using an endoscope, and its absorption rate was evaluated by serial monitoring of the serum concentration and by analysis of its initial 15-min increasing phase.


RESULTS
The duodenal absorption rates of digoxin were 911 +/- 91 ng/min and 506 +/- 76 ng/min for C/C and T/T, respectively (+/- SE, p = 0.007).


CONCLUSIONS
The C3435T mutation of the MDR1 gene is associated with suppression of duodenal absorption of digoxin.
Morita
Yoshinori
Y
Division of Diabetes, Digestive, and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Sakaeda
Toshiyuki
T
Horinouchi
Masanori
M
Nakamura
Tsutomu
T
Kuroda
Kohei
K
Miki
Ikuya
I
Yoshimura
Ken
K
Sakai
Toshiyuki
T
Shirasaka
Daisuke
D
Tamura
Takao
T
Aoyama
Nobuo
N
Kasuga
Masato
M
Okumura
Katsuhiko
K
D000284:Administration, Oral; D002408:Catheters, Indwelling; D004077:Digoxin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D020776:Endoscopes, Gastrointestinal; D005091:Exons / Q000187:drug effects / Q000235:genetics; D019450:Genes, MDR / Q000187:drug effects / Q000235:genetics; D005838:Genotype; D006801:Humans; D007322:Instillation, Drug; D007408:Intestinal Absorption / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D007564:Japan
D004077:Digoxin