S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) The Seoul Journal of Medicine The Seoul Journal of Medicine Vol. 26 No.1 (1985)
Age-Related Changes In Ouabain Pharmacokinetics
Ouabain 약력학적 성질의 연령에 따른 변화
- Shin, Sang-Goo; Park, Chan-Woong; Lee, Kwang-Soo
- Issue Date
- Seoul J Med, Vol.26 No.1, pp. 33-40
- Ouabain; Digitalis glycoside; Rabbits; Pharmacokinetics; Two-compartment model; Serum level; Urinary excretion; Age- related changes; Mechanism of tolerance
- Young animals and humans frequently require higher doses of digitalis glycoside
per kilogram of body weight or per square meter of body surface area than adult to induce
the digitalis effect or toxicity. In order to investigate the pharmacokinetic basis for this observation,
we studied pharmacokinetic properties of the relatively polar and rapidly acting cardiac
glycoside, ouabain, in adult and young rabbits. Consistent with reported observations, we
found no significant difference in transfer coefficients in a linear two compartmental open
model for ouabain pharmacokinetics following a 0.05 mg/kg bolus. However, we found that
young rabbits had larger ouabain volume of distribution per kilogram of body weight than
adults (Vc; 274.36±24.24(S.E.) mllkg vs. 138.29±7.51, Vdss; 1580.61±75.77 mllkg vs.
1056.01±88.18, p<0.005), and a larger systemic clearance (9.18±0.74 mllkg/min vs. 4.67
±0.80, Pnearly twice the serum concentrations at the same dose per kilogram, throughout the experimental
period. Left and right ventricular ouabain concentrations were inversely related to
the volumes of distribution, with significantly higher tissue levels in adult animals.
Although the reason for the difference of tissue sensitivity to a given digitalis glycoside
concentration remains unclear, the result of this study suggests that the pharmacokinetic
difference is responsible for age-related tolerance to digitalis glycoside doses.