Doxorubicin + verapamil

Doxorubicin + verapamil Transferrin (Tf)-conjugated PEG-liposome MDR-leukemia... 

P-gp (ABCB1) Verapamil, digoxin, mitoxantrone, vinblastine, doxorubicin, losartan, talinolol, cortisol, dexamethasone, colchicine, loperamide, domperidone, indinavir, erythromycin, tetracycline, itraconazole, cyclosporine, methotrexate, amitryptyline, phenobarbital, morphine, cimetidine, and others... 

Fig. 20.10. Enhancement of doxorubicin cytotoxicity in LoVo-resistant cells by verapamil and analogues. (Adapted from Ref. [77]). The results are expressed as fold increase in cytotoxicity represented by the ratio of doxorubicin IC50 in the absence and presence of verapamil and analogues (solid bars). The verapamil concentrations used were the minimal cytotoxic concentrations (IC20)-The compounds used were verapamil (1) ...

Bellamy, W.T., Dalton, W.S., Kailey, J.M., Gleason, M.C., McCloskey, T.M., Dorr, R. T. and Alberts, D.S. (1988) Verapamil reversal of doxorubicin resistance in multidrug-resistant human myeloma... 

Drugs that may affect barbiturates include alcohol, charcoal, chloramphenicol, MAO inhibitors, rifampin, and valproic acid. Drugs that may be affected by barbiturates include acetaminophen, anticoagulants, beta blockers, carbamazepine, chloramphenicol, clonazepam, oral contraceptives, corticosteroids, digitoxin, doxorubicin, doxycycline, felodipine, fenoprofen, griseofulvin, hydantoins, methoxyflurane, metronidazole, narcotics, phenmetrazine, phenylbutazone, quinidine, theophylline, and verapamil. 

Oral verapamil has been shown to increase peak plasma levels, prolong the terminal half-life, and increase the volume of distribution at steady state of doxorubicin (282). Gigante et al. (283) performed similar studies in which the pharmacokinetics of doxorubicin in combination with verapamil given at high doses intravenously were followed for 17 patients with advanced neoplasms. The steady-state concentration and systemic and renal clearances were found to be statistically similar for various doses of verapamil and doxorubicin, and for doxorubicin administered alone. 

Gigante M, Toffoli G, Boiocchi M. Pharmacokinetics of doxorubicin co-adminis-tered with high-dose verapamil. Br J Cancer 1995 71(1) 134—136. 

Tab. 5.20 In vitro cytotoxicity of doxorubicin (DOX), idarubicin (IDA), and annanycin (ANN) with and without verapamil (VER) in sensitive HL-60S and resistant HL-60/DOX cells. (Reproduced from Tab. 3 of ref. 127 with permission from the American Society of Hematology)...

Acyclovir Erythromycin Ivermectin Itraconazole Rifampin Actinomycin D Daunorubicin Doxorubicin Docetaxel Epirubicin Etoposide Imatinib Irinotecan Paclitaxel Vinblastine Vincristine Amprenavir Indinavir Nelfinavir Ritonavir Saquinavir Cyclosporine A Tacrolimus Digoxin Quinidine Verapamil Diltiazem Aldosterone Cortisol Corticosterone Dexamethasone Hydrocortisone Cyclosporine Metkephamid Enkephalin... 

Relationship between rat intestinal absorption clearance and lipid solubility. The results shown with the squares represent the relationship between intestinal absorption clearance (ka) observed from the in situ jejunum loop in the presence ( ) and absence ( ) of cyclosporin A in rats and octanol-buffer (pH 7.0) partition coefficients (log D) determined in this study. The numbers refer to 1, atenolol 2, nadolol 3, acetamide 4, celiprolol 5, acebutolol 6, doxorubicin 7, timolol 8, sulfathiazole 9, quinidine 10, sulfamethoxazole 11, digoxin 12, cyclosporin A 13, vinblastine 14, b-estradiol 15, verapamil. Modified from A.Tsuji and I. Tamai. Pham. Res., 13 963—977 (1996). 

Bazargan L, Fouladdel S, Shafiee A, Amini M, Ghaffari SM, Azizi E (2007) Evaluation of anticancer effects of newly synthesized dihydropyridine derivatives in comparison to verapamil and doxorubicin on T47D parental and resistant cell lines in vitro. Cell Biol Toxicol Article (in press) (DOI 10.1007/sl0565-007-9026-x)... 

CALCIUM CHANNEL BLOCKERS DOXORUBICIN t serum concentrations and efficacy of doxorubicin when co-administered with verapamil, nicardipine and possibly diltiazem and nifedipine however, no cases of doxorubicin toxicity have been reported Uncertain however, verapamil is known to inhibit intestinal P-gp, which may t the bioavailability of doxorubicin Watch for symptoms/signs of toxicity (tachycardia, heart failure and hand-foot syndrome)... 

Increased effects (P450 3A4 inhibitors) cimetidine, danazol, diltiazem, erythromycin, troleandomycin, clarithromycin, fluoxetine, isoniazid, niacinamide, nicotinamide, propoxyphene, ketoconazole, itraconazole, verapamil,and valproate Decreased effects (P450 3A4 inducers) cisplatin, doxorubicin, felbamate, rifampin, phenobarbital, phenytoin, primidone, theophylline... 

Figure 12.2. Effects of HT (41°C) or USMH or verapamil (Ver) on cellular uptake of R123 or doxorubicin (DOX) by the parent and MDR variants of human MV522 (human metastatic lung carcinoma) and KB (human epidermoid carcinoma) cell lines. Cellular uptake data are presented as accumulation factors. The accumulation factor for control cells is defined as equal to 1. The accumulation factor for treated cells is defined as the ratio of cellular R123/DOX accumulation in the presence of HT, USMH, or Ver to cellular accumulation in the absence of HT, USMH, or Ver. All experiments were carried out in triplicate.

Figure 12.3. Effects of HT (41°C) or USMH or verapamil (Ver) on cytotoxicity enhancement of doxorubicin (DOX) in the parent or MDR variants of human MV522 and KB cell lines. Data are expressed as % inhibition calculated by the following formula % inhibition = [1 — (counts of viable drug-exposed cells/counts of viable non-drug-exposed cells)] x 100. Cell viability was determined by hemocytometry technique after trypan blue staining. All experiments were carried out in triplicates. P < 0.05 compared to control values.

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