-transparent.png){kind=logo}
The plasma pharmacokinetics of the monoclonal antibody-vinca conjugate KS 1/4-desacetylvinblastine hydrazide (DAVLB-hyd; [3H]LY203725) have been evaluated in rats (17 mg/kg) and monkeys (15 mg/kg) after i.v. dosing. Plasma concentrations of radioactivity 1 hr after dosing were higher in monkeys than in rats. The biphasic elimination of radioactivity in rats was characterized by half-lives (T1/2) of 10 and 143 hr, whereas the elimination of radioactivity in monkeys was characterized by T1/2 values of 11 and 66 hr. Plasma total antibody and radioactivity concentrations were similar within 6 (rat) and 24 (monkey) hr after dosing; however, total antibody concentrations were greater than radioactivity concentrations thereafter, indicating the presence of free antibody in the plasma. Plasma elimination T1/2 values and areas under the curve of total antibody in rats and monkeys were greater than those of radioactivity. The presence of free antibody implies the presence of free DAVLB-hyd; however, plasma concentrations of free DAVLB-hyd were at least 3 orders of magnitude less than those of radioactivity in both species. The T1/2 of free DAVLB-hyd in plasma of LY203725 dosed monkeys was 16 hr. Hydrolysis of the conjugate to yield free DAVLB-hyd was observed upon incubation of conjugate with rat plasma in vitro. Administration of DAVLB-hyd to rats resulted in a rapid initial decrease in plasma DAVLB-hyd followed by a slower (T1/2 = 1.4 hr) elimination rate. Fecal excretion was the predominant mode of elimination of radioactivity in both rats and monkeys dosed with [3H]LY203725.
T D Lindstrom, and
W A Althaus, and
K J Ruterbories, and
D Kau
May 1987,
The Journal of pharmacology and experimental therapeutics,
T D Lindstrom, and
W A Althaus, and
K J Ruterbories, and
D Kau
January 1987,
Drug metabolism and disposition: the biological fate of chemicals,
T D Lindstrom, and
W A Althaus, and
K J Ruterbories, and
D Kau
May 1991,
Cancer research,
T D Lindstrom, and
W A Althaus, and
K J Ruterbories, and
D Kau
January 1990,
Clinical pharmacology and therapeutics,
T D Lindstrom, and
W A Althaus, and
K J Ruterbories, and
D Kau
October 1991,
Pharmaceutical research,
T D Lindstrom, and
W A Althaus, and
K J Ruterbories, and
D Kau
June 1990,
Cancer research,
T D Lindstrom, and
W A Althaus, and
K J Ruterbories, and
D Kau
January 1988,
Targeted diagnosis and therapy,
T D Lindstrom, and
W A Althaus, and
K J Ruterbories, and
D Kau
December 2014,
Xenobiotica; the fate of foreign compounds in biological systems,
T D Lindstrom, and
W A Althaus, and
K J Ruterbories, and
D Kau
January 1986,
New Jersey medicine : the journal of the Medical Society of New Jersey,
T D Lindstrom, and
W A Althaus, and
K J Ruterbories, and
D Kau
August 1990,
Cancer research,
