Dose Proportionality of Bisoprolol Enantiomers in Humans After Oral Administration of the Racemate

Dutta, Atanu Kumar; Lanc, Robert; Begg, Evan J.; Robson, Richard; Sia, Luisa L.; Dukart, Gary; Desjardins, Robert E.; Yacobi, Avraham

doi:10.1002/j.1552-4604.1994.tb02047.x

Cited by 10 publications

(16 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The t 1/2 was the same as those reported by Leopold et al 2 and Dutta et al 16 The Cl tot and Cl r in our study seemed to be smaller than those values reported by other investigators. 2,16 However, when we corrected the Cl tot and Cl r by body weight, the Cl tot (10.3 ( 1.5 L/h/kg) and Cl r (6.7 ( 1.5 L/h/kg) in our study were close to the reported mean values. Therefore, we concluded that the disposition of the bisoprolol in our study was in close agreement with previous reports in the scientific literature.…”

Section: Resultssupporting

confidence: 89%

Pharmacokinetics and Metabolism of Bisoprolol Enantiomers in Humans

Horikiri

Suzuki

Mizobe

1998

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

The plasma concentrations and urinary excretions of bisoprolol enantiomers in four Japanese male healthy volunteers after a single oral administration of 20 mg of racemic bisoprolol were evaluated. The AUC(infinity) and elimination half-life of (S)-(-)-bisoprolol were slightly larger than those of (R)-(+)-bisoprolol in all subjects. The metabolic clearance of (R)-(+)-bisoprolol was significantly (P < 0.05) larger than that of (S)-(-)-bisoprolol (S/R ratio: 0.79+/-0.03), although the difference was small. In contrast, no stereoselective in vitro protein binding of bisoprolol in human plasma was found. An in vitro metabolic study using recombinant human cytochrome P450 (CYP) isoforms indicated that oxidation of both bisoprolol enantiomers was catalyzed by the two isoforms, CYP2D6 and CYP3A4. CYP2D6 metabolized bisoprolol stereoselectively (R > S), whereas the metabolism of bisoprolol by CYP3A4 was not stereoselective. The S/R ratio of the mean clearance due to renal tubular secretion was 0.68, indicating a moderate degree of stereoselective renal tubular secretion. These findings taken together suggest 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.

show abstract

Section: Resultssupporting

confidence: 89%

Pharmacokinetics and Metabolism of Bisoprolol Enantiomers in Humans

Horikiri

Suzuki

Mizobe

1998

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

show abstract

“…It is possible that our assay lacked sufficient sensitivity to allow it to be detected at very low concentrations. Nevertheless, after 5 mg oral doses, peak concentrations in plasma are only 17 ng/mL, so it is perhaps not unexpected that the drug was not detectable in the breast milk …”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, after 5 mg oral doses, peak concentrations in plasma are only 17 ng/mL, so it is perhaps not unexpected that the drug was not detectable in the breast milk. 21…”

Section: Discussionmentioning

confidence: 99%

Breast milk concentrations of amiodarone, desethylamiodarone, and bisoprolol following short‐term drug exposure: Two case reports

Khurana

Jardan

Wilkie

et al. 2014

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Two cases of mothers given postpartum short-term administration of amiodarone, with and without bisoprolol, are described along with determinations of amiodarone and (±)-bisoprolol in the breast milk. In one mother given a cumulative total of amiodarone of 8 g over 1 week, concentrations 11 days after the drug had been stopped were initially deemed sufficient to pose a risk to an infant. Over the next 5 days the concentrations steadily dropped with amiodarone and desethylamiodarone concentrations being found to be at a level comprising minimal risk to the infant. Bisoprolol was not found in the expressed breast milk. In the second case the mother was given a single 150 mg dose of amiodarone and breast milk concentrations were measured on postpartum days 4 and 5. Breast milk amiodarone concentrations were very low and of little concern clinically had the mother breast fed her baby. The risk to the baby of ingesting breast milk after amiodarone administration postpartum depends on the duration of amiodarone exposure, with a single dose posing minimal risk. Bisoprolol does not appear to accumulate to any great extent in breast milk.

show abstract

“…110 However, in poor metabolizers taking metoprolol, the lower S/R ratio leads to less ␤-blockade relative to plasma levels, 111 which tends to cancel the effect of the increased plasma levels of both isomers that is related to the lower oxidation rate. Clinically important stereoselective metabolism does not occur for bisoprolol, 112 nebivolol, 113 or bucindolol (D. Ward, personal communication, 1999).…”

Section: Pharmacokinetic Issuesmentioning

confidence: 99%