Perhexiline is an antianginal drug used for treatment of angina that is not controlled with other drugs.

Indications for measuring

  • Guide dose-adjustment towards optimal drug exposure in relation to drug efficacy and toxicity
    • Significant inter-individual variability in metabolism due to genetic polymorphisms.
      • 5-10% of Caucasian patients are poor metabolisers and will achieve high plasma concentrations (with risk of toxicity) with standard doses
    • Saturable (non-linear) metabolism (i.e. small changes in dosage produce disproportional changes in plasma concentration)
  • Diagnosis
    • Differentiating disease resistant to drug versus inadequate drug exposure (including uncertain adherence)

How to measure

Assay details

Timing of concentration sample

  • With respect to dose interval
    • Perhexiline concentrations should be measured as trough concentrations i.e. just prior to next dose being due
  • With respect to treatment course
    • At steady state (consider practicalities such as testing on weekdays)
      • The standard half-life of perhexiline is 15 hours, with corresponding time to steady state of 3 days. In poor metabolisers half-life will be particularly prolonged e.g. one month.

How to interpret

Reference ranges

Cis-OH-Perhexiline is the predominant perhexiline metabolite. The utility of the perhexiline/metabolite ratio is to inform interpretation of the perhexiline concentration. There is no association between perhexiline/metabolite ratios and clinical response.

  Perhexiline concentration
<0.15 mg/L 0.15-0.6 mg/L >0.6 mg/L

Perhexiline/

metabolite ratio

 

>3 

  • Non-adherence
  • Sample too early in treatment course (not yet at steady state)
  • Poor metaboliser within target
  • Too high a dose, but actually not yet at steady state (expect concentrations to keep rising, potentially to toxic concentrations)
  • Poor metaboliser and hence excessive dose

0.05-3

  • Non-adherence
  • Normal metaboliser and underdosed
  • Sample too early in treatment course (not yet at steady state)
  • Normal metaboliser within target
  • Normal metaboliser and excessive dose
<0.05
  • Non-adherence
  • Ultra-rapid metaboliser and underdosed
  • Sample too early in treatment course (not yet at steady state)
  • Ultra-rapid metaboliser within target
  • Ultra-rapid metaboliser and excessive dose

Factors affecting interpretation

Dose individualisation and adjustment

  • Maintenance dose varies according to individual metaboliser status
    • Usual range 100–250 mg once daily but poor metabolisers may only require only 50 mg weekly whereas ultra-rapid metabolisers (perhexiline/metabolite ratio <0.05) may require up to 500 mg daily.
  • Saturable (non-linear) metabolism (i.e. small changes in dosage produce disproportional changes in plasma concentration).

Contacts for help with interpretation

Medicines Information ph: 03 364 0900

Key Resources

Key References

Horowitz, J. D., Sia, S. T. B., Macdonald, P. S., et al. Perhexiline maleate treatment for severe angina pectoris—Correlations with pharmacokinetics. International Journal of Cardiology. 1986; 13(2):219–29.

Jones, T. E., Morris, R. G., & Horowitz, J. D. Concentration‐time profile for perhexiline and hydroxyperhexiline in patients at steady state. British Journal of Clinical Pharmacology. 2004;57(3): 263–9.

Phuong, H., Choi, B. Y., Chong, C.-R., et al. Can Perhexiline Be Utilized Without Long-Term Toxicity? A Clinical Practice Audit. Therapeutic Drug Monitoring. 2016;38(1):73–8.

Sallustio, B. C., Westley, I. S., & Morris, R. G. Pharmacokinetics of the antianginal agent perhexiline: Relationship between metabolic ratio and steady‐state dose. British Journal of Clinical Pharmacology. 2002;54(2):107–14.

Last updated

May 2024