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Comparison of Pharmacokinetics of Lanoteplase and Alteplase During Acute Myocardial Infarction

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Abstract

Objective

Lanoteplase is a rationally designed variant of tissue plasminogen activator. The aim of this study was to examine the pharmacokinetics and functional activity of a single intravenous bolus dose of lanoteplase with those of a bolus plus two-step infusion of alteplase.

Design

Seven-centre substudy of the InTIME-I angiographic trial in patients presenting within 6 hours of onset of suspected acute myocardial infarction.

Patients and Participants

A total of 31 patients (28 males, 3 females) enrolled in this substudy [mean age 59 (range 26 to 76) years].

Methods

Twenty-three patients randomised to lanoteplase received single bolus doses of 15 kU/kg (n = 5), 30 kU/kg (n = 3), 60 kU/kg (n = 9), or 120 kU/kg (n = 6). Eight patients received alteplase ≤-100mg as a bolus followed by a two-stage 90 min infusion. Blood samples were analysed for antigen concentration and plasminogen activator (PA) activity.

Results

The distribution plasma half-life of approximately 35 min for lanoteplase was at least five times longer than that of alteplase. Lanoteplase plasma clearance averaged 3 L/h (50 ml/min), whereas the mean plasma clearance of approximately 24 L/h (400 ml/min) for alteplase approaches hepatic blood flow following acute myocardial infarction. PA activity after lanoteplase 120 kU/kg remained for 6 hours, compared with less than 4 hours after alteplase 100mg.

Conclusions

The longer antigen and activity half-lives, slower clearance and less complicated administration of lanoteplase compared with alteplase suggest that it may offer advantages for use as a single intravenous bolus to achieve reperfusion after myocardial infarction.

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Notes

  1. Use of tradenames is for product identification only and does not imply endorsement.

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Acknowledgements

This work was supported by a grant from Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ, and was presented in part at the 70th Scientific Session, American Heart Association, Orlando (FL), November 9-12, 1997. We appreciate the insightful scientific input and technical assistance provided by Drs. Floyd Beierle and Barbara Ameer during the conduct of the study and the preparation of this manuscript.

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Authors and Affiliations

  1. Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey, USA

    John B. Kostis

  2. Bristol-Myers Squibb, Route 206 and Province Line Road, PO Box 4000, Princeton, New Jersey, 08640, USA

    Randy C. Dockens, Nimish Vachharajani, Ralph H. Raymond, Bruce C. Stouffer, Lee K. Tay, Wen Chyi Shyu & Weichi Liao

  3. Health Sciences Center, University of Oklahoma, Oklahoma City, Oklahoma, USA

    Udho Thadani

  4. Slidell Memorial Hospital, Slidell, Louisiana, USA

    Vasnath Bethala

  5. University of Florida, Jacksonville, Florida, USA

    Carl Pepine

  6. Oklahoma Heart Center, Tulsa, Oklahoma, USA

    Wayne Leimbach

  7. Presently at Covance Inc., Princeton, New Jersey, USA

    Weichi Liao

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  1. John B. Kostis
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  2. Randy C. Dockens
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Correspondence to Randy C. Dockens.

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Kostis, J.B., Dockens, R.C., Thadani, U. et al. Comparison of Pharmacokinetics of Lanoteplase and Alteplase During Acute Myocardial Infarction. Clin Pharmacokinet 41, 445–452 (2002). https://doi.org/10.2165/00003088-200241060-00005

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