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Metoclopramide kinetics at high‐dose infusion rates for prevention of cisplatin‐induced emesis
Author(s) -
Saller R,
Hellenbrecht D,
Briemann L,
Hellstern A,
Hess H,
Mitrou P,
Hodgson M,
Achtert G,
Brockmann P,
Hausleiter H J
Publication year - 1985
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1985.9
Subject(s) - metoclopramide , cisplatin , kinetics , pharmacology , medicine , anesthesia , vomiting , chemotherapy , physics , quantum mechanics
Eleven male subjects aged 24 to 58 yr received cisplatin, 90 to 120 mg/m 2 iv, in combination with other cytostatic drugs such as doxorubicin HC1 and bleomycin. To prevent emesis, two high‐dose metoclopramide regimens were started 2 hr before cytostatic therapy. Regimen A (n = 7) consisted of a loading dose infusion of 1 mg/kg/hr over 2 hr, followed by a maintenance infusion of 0.5 mg/kg/hr over 24 hr (total dose was 14 mg/kg in each cytostatic cycle). Regimen B (n = 6) consisted of half the metoclopramide dose. The following kinetics were derived from the metoclopramide steady‐state plasma levels and the t½ of the elimination phase 26 to 38 hr after dosing (median value and range are listed): Steady‐state plasma concentration in group A and group B was 750 (480 to 1520) and 360 (300 to 480) ng/ml plasma. Drug clearance in group A and group B was 0.67 (0.3 to 1.0) and 0.70 (0.5 to 0.8) l /hr/kg. Volumes of drug distribution in group A and group B were 4.4 (1.9 to 6.5) and 4.3 (3.2 to 5.9) l /kg. Values for the t½ in the elimination phase in group A and group B were 4.7 (3.0 to 5.4) and 4.3 (3.7 to 5.1) hr. It appears that metoclopramide kinetics at high doses were dose linear, i.e., without evidence of cumulation. There were few side effects; vomiting was effectively suppressed by both regimens. Clinical Pharmacology and Therapeutics (1985) 37, 43–47; doi: 10.1038/clpt.1985.9