Pharmacokinetics and Metabolism of Bisoprolol-14C in Three Animal Species and in Humans

  title={Pharmacokinetics and Metabolism of Bisoprolol-14C in Three Animal Species and in Humans},
  author={K. U. B{\"u}hring and Holger Sailer and H. P. Faro and G. Leopold and Joachim Pabst and A. Garbe},
  journal={Journal of Cardiovascular Pharmacology},
&NA; The pharmacokinetic properties of bisoprolol‐14C were studied in Wistar rats, beagle dogs, and Cynomolgus monkeys. Bisoprolol is well absorbed in these species; independent of the route of administration (i.v. or p.o.), 70‐90% of the 14C‐dose was recovered in urine. Faecal excretion was ˜20% in rats and <10% in dogs and monkeys. Rats excreted ˜ 10% of the dose in bile after i.v. as well as after oral administration. The plasma half‐life of the unchanged drug was ˜ 1 h in rats, 3 h in… 
Metabolic Fate of the New β-Adrenoceptor Antagonist, Bisoprolol, in Animals (1) : Absorption, Distribution and Excretion of 14C-Bisoprolol in Rats
The absorption, distribution and excretion of bisoprolol were studied in rats after oral or intravenous administration of 14C-bisoproll and whole body autoradiograms obtained with pigmented rats demonstrated that specific binding of radioactivity to melanin containing tissues was noticed.
Comparison of the pharmacokinetic properties of bisoprolol and carvedilol in healthy dogs.
Differences suggested that, in dogs, bisoprolol has less interindividual pharmacokinetic variability, compared with carvedilol, a third-generation beta1/beta2 and alpha1-adrenoceptor blocking agent.
Metabolic Fate of the New β-Adrenoceptor Antagonist, Bisoprolol, in Animals (2) : Tissue Accumulation after Consecutive Oral Administration of 14C-Bisoprolol in Rats
There was not any accumulation of the drug and its metabolites in the organs and tissues of rats following the consecutive oral administration of 14C-bisoprolol, and radioactivity levels in most tissues decreased near the detection limit in either administration group.
Metabolic Fate of the New β-Adrenoceptor Antagonist, Bisoprolol, in Animals (3) : Foeto-placental Transfer and Excretion into Milk of 14C-Bisoprolol in Rats
Pregnant rats and lactating rats after the oral or intravenous administration of 14C-bisoprolol showed very little radioactivity was transferred to fetuses through the placenta in either route of the drug administration and the time course of radioactivity in the milk was similar to that in plasma.
Stereoselective pharmacokinetics of bisoprolol after intravenous and oral administration in beagle dogs.
It is concluded that the stereoselective difference in the metabolic clearance between S(-)- and R(+)-bisoprolol caused the difference inThe disposition of bisoproll enantiomers.
Pharmacokinetics and metabolism of bisoprolol enantiomers in humans.
It is suggested that the small differences in the pharmacokinetics between (S)-(-)- and (R)-(+)-bisoprolol are mainly due to the stereoselectivity in the intrinsic metabolic clearance by CYP2D6 and renal tubular secretion.
Pharmacokinetics and pharmacodynamics of bisoprolol in rats with bilateral ureter ligation-induced renal failure.
The results suggested that renal excretion and hepatic metabolism of bisoprolol were significantly reduced in BUL rats, but that pharmacodynamics of bisOProlol was not altered by acute renal failure.
Dose Proportionality of Bisoprolol Enantiomers in Humans After Oral Administration of the Racemate
Findings support dose proportionality and absence of stereoselective pharmacokinetics for bisoprolol in the dose range studied.
Population Pharmacokinetic Analysis of Bisoprolol
The technique of population pharmacokinetic analysis was employed to study the variability in the dose concentration relationship of bisoprolol during its clinical development, predicting that progressive increases in serum creatinine or aspartate transaminase activity will result in only a 50% reduction of clearance.
Utility of cryopreserved hepatocytes suspended in serum to predict hepatic clearance in dogs and monkeys.
The utility of commercially available cryopreserved preparations of dog and monkey hepatocytes for the in vitro-in vivo correlation analyses with the aid of empirically or biologically obtained scaling factors at the early development stage of new drug candidates is demonstrated.