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Clinical pharmacokinetics of procainamide infusions in relation to acetylator phenotype

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Abstract

The pharmacokinetics of procainamide was determined in 21 lidocaine-resistant patients who received the drug according to a pharmacokinetically designed double-infusion technique. Thirteen patients were phenotyped as slow acetylators, seven as fast, and one as intermediate. The total body clearances (ClT) of PA in slow and fast acetylators were 22.6 and 34.8 liters/hr, respectively. The fraction of PA cleared by the formation of NAPA in the corresponding acetylator group was 0.2 and 0.4. Renal impairment affected the pharmacokinetics of PA more profoundly as the ClTs of PA in patients with and without renal impairment were 17.9 and 31.2 liters/hr, respectively. None of the calculated volumes of distribution was affected by acetylator phenotype or renal impairment. These data identify the contribution of at least two of the major factors accounting for variability in PA disposition in patients undergoing therapy.

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Abbreviations

PA:

Procainamide

NAP A:

N-Acetylprocainamide

LI:

Loading infusion

MI:

Maintenance infusion

V p :

Volume of central compartment for PA

V t :

Volume of tissue compartment for PA

V dss :

Volume of distribution of PA at steady state

V dβ :

Volume of distribution of PA during postdistributive phase

Cl12 :

Intercompartmental clearance of PA

Cl T :

Total body clearance of PA

Cl R :

Renal clearance of PA

Cl A :

Acetylation clearance of PA

ClAP :

Apparent acetylation clearance of PA

Cl M :

Metabolic (nonacetylation) clearance of PA

C PA :

Serum concentration of PA

C t :

Tissue concentration of PA

C ssPA :

Steady-state serum concentration of PA

V n :

Volume of distribution of NAPA

Cl N :

Renal clearance of NAPA

Cl0 :

Nonrenal clearance of NAPA

ClBN :

Total body clearance of NAPA

C NAPA :

Serum concentration of NAPA

C ssN :

Steady-state serum concentration of NAPA

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, 14260, Amherst, New York

    John J. Lima &  William J. Jusko

  2. Department of Medicine, School of Medicine, State University of New York at Buffalo, 14214, Buffalo, New York

    David R. Conti, Allen L. Goldfarb & Lawrence H. Golden

  3. Department of Forensic Chemistry, University of Strathclyde, Glasgow, Scotland

    William J. Tilstone

Authors
  1. John J. Lima
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  2. David R. Conti
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  3. Allen L. Goldfarb
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  4. William J. Tilstone
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  5. Lawrence H. Golden
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  6. William J. Jusko
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Additional information

This work was supported by Grants 20852 and 24211 from the National Institutes of General Medical Sciences, National Institutes of Health.

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Lima, J.J., Conti, D.R., Goldfarb, A.L. et al. Clinical pharmacokinetics of procainamide infusions in relation to acetylator phenotype. Journal of Pharmacokinetics and Biopharmaceutics 7, 69–85 (1979). https://doi.org/10.1007/BF01059442

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