April 1, 1994Journal of Cardiovascular Pharmacology
Relationships Between Acute and Chronic β-Blocking Effects of Bisoprolol in Healthy Volunteers: A Practical Approach to Predict Intensity of β-Blockade
Why the study?
Can the steady-state beta-blocking effect of oral bisoprolol be predicted by the plasma concentration-effect relationship after an acute i.v. dose in healthy volunteers?
Population
10 healthy volunteers
Comparison
Bisoprolol 5 mg i.v. infusion over 5 min… vs Placebo i.v. infusion (cross-over design)
Design
RCT, randomized, cross-over, double-blind
Follow-up
48 hours after i.v. dose, then 5 days of oral dosing
Authors
Discussion
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Implication
Acute IV PK/PD modeling predicts steady-state oral beta-blockade; extends individualized dosing strategies for clinicians and validates PK/PD approaches for researchers.
Key Points
- To determine whether steady-state beta-blocking effects of chronic oral bisoprolol can be predicted using a mathematical concentration-effect model derived from an acute intravenous dose.
- Conducted a double-blind, randomized, cross-over, placebo-controlled trial in 10 healthy volunteers receiving a 5-minute intravenous infusion of 5 mg bisoprolol or placebo, followed by serial standardized exercise tests and HPLC plasma assays over 48 hours.
- Following a 1-week washout, participants received oral bisoprolol (10 mg once daily) for 5 days, with exercise tests and simultaneous plasma level measurements performed on day 5 before and 2, 3, and 4 hours post-dose.
- Acute intravenous bisoprolol significantly decreased exercise heart rate compared with placebo, producing a peak reduction of -20.5 ± 4%.
- A direct concentration-effect relationship without hysteresis was established using sigmoid (n=7) or linear (n=3) best-fit models.
- Following repeated oral dosing, 88% of the observed decreases in exercise heart rate at steady state fell within the 95% confidence interval of individual model predictions.
Structured PICO
Can the steady-state beta-blocking effect of oral bisoprolol be predicted by the plasma concentration-effect relationship after an acute i.v. dose in healthy volunteers?
P
Population
10 healthy volunteers
I
Intervention
Bisoprolol 5 mg i.v. infusion over 5 min, followed by a 1-week interval and then oral bisoprolol 10 mg once daily for 5 days
C
Comparator
Placebo i.v. infusion (cross-over design)
O
Outcome
Relationship between beta-blockade (exercise heart rate decrease) and plasma concentrations of bisoprololsurrogate
The intensity of bisoprolol-induced beta-blockade after repeated oral dosing can be accurately predicted by a single-test i.v. dose administration.
Cite This Study
Jamin et al. (1994) studied this question.