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.
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References
Ballet F, Barbore JC, Poupon R (1984) Hepatic extraction of adriamycin in patients with hepatocellular carcinoma. Eur J Clin Oncol 20 (6) 761–764
Bevington PR (1969) Data reduction and error analysis for the physical sciences. McGraw-Hill, New York, pp 235–236
Burnakis TG, Seldon FD, Czaplicki AD (1983) Increased serum theophylline concentrations secondary to oral verapamil. Clin Pharm 2: 458–461
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
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
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
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
Kaye S, Merry S (1985) Tumour cell resistance to anthracyclines—a review. Cancer Chemother Pharmacol 14 (2) 96–103
MacPhee GJA, McInnes GT, Thompson GG, Brodie MJ (1986) Verapamil potentiates carbomarzepine neurotoxicity a clinically relevant inhibitory interaction. Lancet (in press)
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
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
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
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
Renton KW (1985) Inhibition of hepatic microsomal drug metabolism by the calcium channel blockers diltiazem and verapamil. Biochem Pharmacol 34 2549–2553
Riggs CE Jr, Benjamin RS, Serpick A, Bachur NR (1977) Biliary disposition of adriamycin. Clin Pharmac Ther 22 234–238
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
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
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
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
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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
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DOI: https://doi.org/10.1007/BF00273394