Direct determination of distribution volume and disappearance rate of native creatine kinase in humans

Area of Science:

• Biochemistry
• Cardiology
• Pharmacokinetics

Background:

• Accurate estimation of myocardial infarct size requires characterizing creatine kinase (CK) distribution volume (DV) and disappearance rate (Kd).
• Existing human values for CK DV and Kd are extrapolated from experimental models.
• These parameters are crucial for enzymatic assessment of infarct size.

Purpose of the Study:

• To characterize the distribution volume (DV) and disappearance rate (Kd) of native creatine kinase (CK) in human patients with acute myocardial infarction.
• To determine if a one-compartment model is suitable for clinical application of CK parameters.
• To investigate the correlation between CK Kd estimated post-infarction and calculated after reinfused plasma.

Main Methods:

• Collected enzyme-rich plasma from 10 acute myocardial infarction patients during hemodynamic monitoring.
• Reinfused plasma after CK serum activity returned to baseline and collected blood samples over 12 hours.
• Analyzed total CK, MM-CK, and MB-CK concentrations using spectrophotometry and radioimmunoassay, with data analyzed via nonlinear least-squares approximation or noncompartmental approach.

Main Results:

• Concentrations of immunologically active CK molecules declined in parallel to enzymatic activity.
• A single exponential decay was observed in most patients, yielding a Kd of 0.0023 +/- 0.00057 min⁻¹.
• The average DV was 3284 +/- 693 ml (5% of body weight), and no correlation was found between pre- and post-reinfusion Kd estimates.

Conclusions:

• A one-compartment model utilizing CK Kd and DV values compatible with plasma volume is suitable for clinical use.
• The true CK disappearance rate (Kd) cannot be accurately determined from the terminal portion of CK time-activity curves following acute infarction.
• This study provides essential pharmacokinetic data for creatine kinase in myocardial infarction patients.