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Acivicin was administered iv to rhesus monkeys bearing Ommaya reservoirs, and serial blood and cerebrospinal fluid (CSF) samples were collected and analyzed to determine the time course of drug concentrations in these body fluids. After iv doses of 4 or 20 mg/kg (50 or 250 mg/m2), acivicin plasma concentrations demonstrated a rapid initial decline (distribution phase), and then declined exponentially with a terminal (elimination phase) half-life of 3--4 hrs. CSF concentrations increased over a period of 2--2.5 hrs, reaching peak values of 2.0--2.7 micrograms/ml at 20 mg/kg and 0.3--0.5 microgram/ml at 4 mg/kg; thereafter, CSF levels declined in parallel with plasma, with a CSF/plasma concentration ratio of 0.10--0.17. A three-compartment pharmacokinetic model gave a close fit of predicted and observed plasma and CSF concentration data. Significant and predictable CSF penetration by iv administered acivicin in monkeys is consistent with observation of CNS side effects in patients in the phase I clinical trial and suggests that acivicin should be evaluated in the treatment of CNS malignancies and metastases.
J P McGovren, and
J C Stewart, and
G L Elfring, and
R B Smith, and
N Soares, and
J H Wood, and
D G Poplack, and
D D Von Hoff
May 1985,
Cancer research,
J P McGovren, and
J C Stewart, and
G L Elfring, and
R B Smith, and
N Soares, and
J H Wood, and
D G Poplack, and
D D Von Hoff
June 1995,
Antimicrobial agents and chemotherapy,
J P McGovren, and
J C Stewart, and
G L Elfring, and
R B Smith, and
N Soares, and
J H Wood, and
D G Poplack, and
D D Von Hoff
September 1987,
Pain,
J P McGovren, and
J C Stewart, and
G L Elfring, and
R B Smith, and
N Soares, and
J H Wood, and
D G Poplack, and
D D Von Hoff
February 2015,
Comparative medicine,
J P McGovren, and
J C Stewart, and
G L Elfring, and
R B Smith, and
N Soares, and
J H Wood, and
D G Poplack, and
D D Von Hoff
October 1999,
Drug metabolism and disposition: the biological fate of chemicals,
J P McGovren, and
J C Stewart, and
G L Elfring, and
R B Smith, and
N Soares, and
J H Wood, and
D G Poplack, and
D D Von Hoff
November 1981,
Cancer research,
J P McGovren, and
J C Stewart, and
G L Elfring, and
R B Smith, and
N Soares, and
J H Wood, and
D G Poplack, and
D D Von Hoff
January 1980,
Journal of medical primatology,
J P McGovren, and
J C Stewart, and
G L Elfring, and
R B Smith, and
N Soares, and
J H Wood, and
D G Poplack, and
D D Von Hoff
May 1990,
Annals of neurology,
J P McGovren, and
J C Stewart, and
G L Elfring, and
R B Smith, and
N Soares, and
J H Wood, and
D G Poplack, and
D D Von Hoff
January 1992,
Hormone research,
J P McGovren, and
J C Stewart, and
G L Elfring, and
R B Smith, and
N Soares, and
J H Wood, and
D G Poplack, and
D D Von Hoff
January 1985,
Psychopharmacology,
