-transparent.png){kind=logo}
The disposition and safety of the antiviral drug acyclovir were studied in 14 subjects with advanced malignancies. Acyclovir was administered by a 1-hr intravenous infusion at doses of 0.5, 1.0, 2.5, and 5.0 mg/kg. At the end of infusion, mean peak plasma levels (+/- SEM), determined by radioimmunoassay, were 6.4 +/- 0.7, 12.1 +/- 2.3, 14.9 +/- 2.7, and 33.7 +/- 7.1 microM. The plasma concentration-time profiles could be described by a biexponential equation. The half-life of acyclovir in the slow disposition phase ranged from 2.2 to 5 hr and the drug was detected in the plasma for at least 18 hr after infusion. The total body clearance ranged from 117 to 396 ml/min/1.73 m2. A proportionality between area under the curve and dose suggests that acyclovir exhibits dose-independent kinetics in the dose range studied. There was wide variation in cumulative urinary excretion of unchanged drug, ranging from 30 to 69% of the dose. From renal clearances of acyclovir, which were higher than creatinine clearances, it appears that both glomerular filtration and tubular secretion contribute to its renal excretion. Analysis of the urine by reverse-phase high-performance liquid chromatography revealed the presence of the metabolite 9-carboxymethoxymethylguanine. There was no indication of toxicity either clinically or from laboratory findings in any of the study subjects. This study demonstrates that in addition to selectivity and low toxicity, the kinetic profile and metabolic disposition of acyclovir make it an attractive candidate for therapy in a variety of herpes infections.
P de Miranda, and
R J Whitley, and
M R Blum, and
R E Keeney, and
N Barton, and
D M Cocchetto, and
S Good, and
G P Hemstreet, and
L E Kirk, and
D A Page, and
G B Elion
December 2007,
Antimicrobial agents and chemotherapy,
P de Miranda, and
R J Whitley, and
M R Blum, and
R E Keeney, and
N Barton, and
D M Cocchetto, and
S Good, and
G P Hemstreet, and
L E Kirk, and
D A Page, and
G B Elion
January 1987,
Therapie,
P de Miranda, and
R J Whitley, and
M R Blum, and
R E Keeney, and
N Barton, and
D M Cocchetto, and
S Good, and
G P Hemstreet, and
L E Kirk, and
D A Page, and
G B Elion
July 1982,
The American journal of medicine,
P de Miranda, and
R J Whitley, and
M R Blum, and
R E Keeney, and
N Barton, and
D M Cocchetto, and
S Good, and
G P Hemstreet, and
L E Kirk, and
D A Page, and
G B Elion
August 2000,
Critical care medicine,
P de Miranda, and
R J Whitley, and
M R Blum, and
R E Keeney, and
N Barton, and
D M Cocchetto, and
S Good, and
G P Hemstreet, and
L E Kirk, and
D A Page, and
G B Elion
October 2004,
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism,
P de Miranda, and
R J Whitley, and
M R Blum, and
R E Keeney, and
N Barton, and
D M Cocchetto, and
S Good, and
G P Hemstreet, and
L E Kirk, and
D A Page, and
G B Elion
January 1985,
Journal of cardiovascular pharmacology,
P de Miranda, and
R J Whitley, and
M R Blum, and
R E Keeney, and
N Barton, and
D M Cocchetto, and
S Good, and
G P Hemstreet, and
L E Kirk, and
D A Page, and
G B Elion
January 1976,
Arzneimittel-Forschung,
P de Miranda, and
R J Whitley, and
M R Blum, and
R E Keeney, and
N Barton, and
D M Cocchetto, and
S Good, and
G P Hemstreet, and
L E Kirk, and
D A Page, and
G B Elion
September 1983,
The Journal of antimicrobial chemotherapy,
P de Miranda, and
R J Whitley, and
M R Blum, and
R E Keeney, and
N Barton, and
D M Cocchetto, and
S Good, and
G P Hemstreet, and
L E Kirk, and
D A Page, and
G B Elion
April 1983,
The Medical letter on drugs and therapeutics,
P de Miranda, and
R J Whitley, and
M R Blum, and
R E Keeney, and
N Barton, and
D M Cocchetto, and
S Good, and
G P Hemstreet, and
L E Kirk, and
D A Page, and
G B Elion
January 1977,
Infection,
