Genetic influences on the pharmacokinetics of orally and intravenously administered digoxin as exhibited by monozygotic twins.
The expression and function of the drug transporter P-glycoprotein are highly variable. Environmental and genetic factors contribute to this variation. We studied the disposition of digoxin, a frequently used probe drug for P-glycoprotein function in humans, in monozygotic (MZ) twins and found that digoxin pharmacokinetics after oral and intravenous administration are highly correlated within MZ twins, supporting the hypothesis of a robust contribution from genetic variance. Our study suggests that studies involving twins could be more widely applied to elucidate pharmacogenetics.
Experimental and Clinical Research Center, Franz-Volhard Clinic, Helios Klinikum-Berlin and Medical Faculty of the Charité, Berlin, Germany.
A L
AL
Birkenfeld
J
J
Jordan
U
U
Hofmann
A
A
Busjahn
G
G
Franke
N
N
Krüger
S
S
Igel
T
T
Mürdter
S
S
Drescher
S
S
Shi
S
S
Engeli
M
M
Schwab
M
M
Eichelbaum
F C
FC
Luft
M F
MF
Fromm
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000284:Administration, Oral; D000328:Adult; D003903:Deuterium; D004077:Digoxin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010641:Phenotype; D010865:Pilot Projects; D012042:Registries; D014430:Twins, Monozygotic / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004077:Digoxin; D003903:Deuterium