What is the clinical evidence from this study?

Study design: Other. Intervention: Recombinant tissue-type plasminogen activator (rt-PA) vs. Standard 3 h regimen. Primary outcome: Alteplase plasma concentration versus time profiles.

What does this research mean for the field?

Accelerated and double-bolus regimens of rt-PA yield higher initial plasma concentrations and greater alpha 2-antiplasmin depletion than standard 3-hour infusion, providing a pharmacokinetic explanation for higher patency rates. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To determine whether pharmacokinetic differences across accelerated, standard, and double-bolus dosing regimens explain the improved vessel patency seen with rapid rt-PA delivery.

January 1, 1998Biopharmaceutics & Drug Disposition

Pharmacokinetics and pharmacodynamics of recombinant tissue-type plasminogen activator following intravenous administration in rabbits: a comparison of three dosing regimens

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Key result

Accelerated and double-bolus rt-PA regimens produce higher initial plasma concentrations than standard infusions.

Why the study?

Several clinical trials suggested higher patency rates with rapid rt-PA administration, but pharmacokinetic explanations were unclear.

Population

Rabbits

Comparison

Accelerated 90 min vs standard 3 h vs double-bolus rt-PA dosing regimens

Design

Pharmacokinetic and pharmacodynamic study

Authors

SEStephen EpplerCytokinetics (United States)TSTaurence Senn EGEllen GilkersonSunesis (United States)

Discussion

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Implication

Accelerated alteplase regimens yield higher initial plasma levels in rabbits; leaves open whether this drives improved patency in human MI.

Key Points

To determine whether pharmacokinetic differences across accelerated, standard, and double-bolus dosing regimens explain the improved vessel patency seen with rapid rt-PA delivery.
Administered recombinant tissue-type plasminogen activator (alteplase) intravenously to rabbits using three dosing strategies: an accelerated 90-minute infusion, a standard 3-hour infusion, and a double-bolus regimen.
Measured plasma drug concentration profiles over time, calculated intrinsic metabolic clearance with a Michaelis-Menten model, and tracked alpha 2-antiplasmin depletion.
Accelerated and double-bolus regimens generated higher initial rt-PA plasma concentrations than the standard 3-hour infusion.
Double-bolus administration showed slower plasma clearance than both infusion regimens—consistent with clearance saturation and an estimated Vmax/Km intrinsic metabolic clearance of 14–19 h⁻¹—and produced 29% maximum depletion of alpha 2-antiplasmin versus approximately 15% with the infusions.

PICO

Population

Rabbits evaluated for rt-PA pharmacokinetics following three different dosing regimens.

Intervention / Comparator

Recombinant tissue-type plasminogen activator (rt-PA) vs Standard 3 h regimen (Accelerated 90 min and double-bolus regimen)

Primary Outcome

Alteplase plasma concentration versus time profiles

Cite This Study

Eppler et al. (1998) studied this question. Recombinant tissue-type plasminogen activator (rt-PA) vs. Standard 3 h regimen was evaluated on Alteplase plasma concentration versus time profiles. Accelerated and double-bolus regimens of rt-PA resulted in higher initial plasma concentrations compared to the standard 3-hour regimen in rabbits.

synapsesocial.com/papers/6ab2409343445d4dc35f8a45 https://doi.org/10.1002/(sici)1099-081x(199801)19:1<31::aid-bdd68>3.0.co;2-g

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Implication

Accelerated alteplase regimens yield higher initial plasma levels in rabbits; leaves open whether this drives improved patency in human MI.

Pharmacokinetics and pharmacodynamics of recombinant tissue-type plasminogen activator following intravenous administration in rabbits: a comparison of three dosing regimens

Discussion

Member takes

Implication

Key Points

PICO

Cite This Study

Pharmacokinetics and pharmacodynamics of recombinant tissue-type plasminogen activator following intravenous administration in rabbits: a comparison of three dosing regimens

Discussion

Member takes

Implication

Key Points

PICO

Cite This Study

Also Consider

Also Consider