Influence of polysorbate 80 (Tween 80) and etoposide (VP-16-213) on the pharmacokinetics and urinary excretion of adriamycin and its metabolites in cancer patients.
Polysorbate 80 (Tween 80) is present in the IV pharmaceutical preparation of VP-16-213 marketed as VePesid (Bristol-Myers) (etoposide 100 mg, benzylalcohol 150 mg, polyethylene glycol 300 3250 mg, citric acid 10 mg, Tween 80 400 mg and absolute alcohol to 5 ml per 100 mg ampule of VP16), to increase its miscibility with blood. We have examined the effects of 400 mg/m2 Tween 80 IV and 100 mg/m2 VP16 on the pharmacokinetics of Adriamycin (ADR, 30 or 40 mg/m2). ADR and metabolite concentrations were measured by HPLC. ADR plasma profiles were best fitted to a bi-exponential decay and a two-compartment open model. Tween 80 did not alter the values of the two ADR half-lives, nor did it affect metabolite kinetics of their urinary excretion. However, in a similar manner and consistently in all patients, both Tween 80 and VP16 increased the volume of distribution of the central compartment for ADR up to 3-fold, decreased the AUC of ADR up to 2-fold and increased its clearance by exactly the same amount. These effects were due to reduced plasma ADR concentrations during the early phase of its kinetics. Urinary excretion of ADR was also increased. In conclusion, VP16 is likely to affect the kinetics of drugs administered with it: early plasma concentrations will fall due to a general physiological effect of Tween 80 on the apparent volume of circulation.
J
J
Cummings
G J
GJ
Forrest
D
D
Cunningham
N L
NL
Gilchrist
M
M
Soukop
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D004317:Doxorubicin / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D004347:Drug Interactions; D005047:Etoposide / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D014677:Pharmaceutical Vehicles; D011034:Podophyllotoxin / Q000031:analogs & derivatives*; D011136:Polysorbates / Q000494:pharmacology*
D014677:Pharmaceutical Vehicles; D011136:Polysorbates; D005047:Etoposide; D004317:Doxorubicin; D011034:Podophyllotoxin