Skip to main content
Log in

The effect of verapamil on the pharmacokinetics of adriamycin

  • Original Articles
  • Verapamil, Adriamycin Pharmacokinetics
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Summary

The concurrent administration of adriamycin (intravenous) and verpamil (oral) is of considerable interest because of experimental data suggesting that resistance to adriamycin may be overcome by this means. The potential for a pharmacokinetic interaction between the two drugs has therefore been investigated in five patients with small cell lung cancer treated with combination chemotherapy comprising adriamycin, VP16, vincristine and cyclophosphamide. The data indicate that a significant interaction takes place. Adriamycin peak levels, terminal halflife and the volume of distribution at steady state are higher, whereas plasma drug clearance and the volume of the central compartment are lower with co-administration of verapamil. There was no evidence of enhanced drug toxicity in this study; however, the data should be considered in the interpretation of clinical trials in which adriamycin and verapamil are used together, both in terms of toxicity and tumour response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Ballet F, Barbore JC, Poupon R (1984) Hepatic extraction of adriamycin in patients with hepatocellular carcinoma. Eur J Clin Oncol 20 (6) 761–764

    Google Scholar 

  2. Bevington PR (1969) Data reduction and error analysis for the physical sciences. McGraw-Hill, New York, pp 235–236

    Google Scholar 

  3. Burnakis TG, Seldon FD, Czaplicki AD (1983) Increased serum theophylline concentrations secondary to oral verapamil. Clin Pharm 2: 458–461

    Google Scholar 

  4. Cole SCJ, Flanoyan RJ, Johnston A, Holt DW (1981) Rapid high performance liquid chromatographic method for the measurement of verapamil and norverapamil in blood plasma or serum. J Chromatogr 218 621–629

    Google Scholar 

  5. Cummings J, Stuart JFB, Calman KC (1984) Determination of adriamycin, adriamycinol and their 7-deoxyaglycones in human serum by high-performance liquid chromatography. J Chromatogr 311 125–133

    Google Scholar 

  6. Gurto HL, Gessner T, Culliton P (1976) Studies on the effects of cyclophosphamide, vincristine and prednisolone on some hepatic oxidations and conjugations. Cancer Treat Rep 60 1261–1285

    Google Scholar 

  7. Kaelin WG Jr, Shrivastar S, Shard DG, Jirtle RL (1982) Effect of verapamil on malignant tissue blood flow in SMT-2A tumour bearing rats. Cancer Res 42 3944–3949

    Google Scholar 

  8. Kaye S, Merry S (1985) Tumour cell resistance to anthracyclines—a review. Cancer Chemother Pharmacol 14 (2) 96–103

    Google Scholar 

  9. MacPhee GJA, McInnes GT, Thompson GG, Brodie MJ (1986) Verapamil potentiates carbomarzepine neurotoxicity a clinically relevant inhibitory interaction. Lancet (in press)

  10. Meredith PA, Elliott HL, Posanisi F, Kelman AW, Sumner DJ, Reid JL (1985) Verapamil pharmacokinetics and apparent hepatic and renal blood flow. Br J Clin Pharm 20 101–107

    Google Scholar 

  11. Mullerleile V, Garbrecht M, Hanrath P, Langerstein BA, Bieber K, Bleifeld W, Hassfeld DK (1984) Mℷliche Pr⇑ention der Adriamycin-induzierten Kardiomyopathie durch Verapamil Klin Wochenschr 62 1032–1037

    Google Scholar 

  12. Ozols RF, Rogan AM, Hamilton TC, Klecker R, Young RC (1984) Verapamil plus adriamycin in refractory ovarian cancer design of a clinical trial on basis of reversal of adriamycin resistance in human ovarian cancer cell lines. AACR abstract 1186

  13. Presant CA, Kennedy P, Wiseman C, Gala K, Wyres M (1984) Verapamil plus adriamycin — a phase I-II clinical study. Proc Am Soc Clin Oncol 3 1–124

    Google Scholar 

  14. Renton KW (1985) Inhibition of hepatic microsomal drug metabolism by the calcium channel blockers diltiazem and verapamil. Biochem Pharmacol 34 2549–2553

    Google Scholar 

  15. Riggs CE Jr, Benjamin RS, Serpick A, Bachur NR (1977) Biliary disposition of adriamycin. Clin Pharmac Ther 22 234–238

    Google Scholar 

  16. Tsuruo T, Iidu H, Tsukagoshi S, Sakurai Y (1982) Increased accumulation of vincristine and adriamycin in drug-resistant P388 tumour cells following incubation with calcium antagonists and calmodulin inhibitors. Cancer Res 42 4730–4733

    Google Scholar 

  17. Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y (1983) Potentiation of vincristine and adriamycin effects in human haemopotietic tumour cell lines by calcium antagonists and calmodulin inhibitors. Cancer Res 43 2267–2272

    Google Scholar 

  18. Tsuruo T, Iida H, Nojiri M, Tsukagoshi S, Sakurai Y (1983) Circumvention of vincristine and adriamycin resistance in vitro and in vivo by calcium influx blockers. Cancer Res 43 2905–2910

    Google Scholar 

  19. Yalowich JC, Zucati JR, Gross MA, Ross WE (1985) Effects of verapamil on etoposide, vincristine and adriamycin activity in normal human bone marrow granulocyte-macrophage progenitors and in human K562 leukaemia cells in vitro. Cancer Res 45 4921–4924

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kerr, D.J., Graham, J., Cummings, J. et al. The effect of verapamil on the pharmacokinetics of adriamycin. Cancer Chemother. Pharmacol. 18, 239–242 (1986). https://doi.org/10.1007/BF00273394

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00273394

Keywords

Navigation