Landersdorfer, C. B., Kirkpatrick, C. M. J., Kinzig-Schippers, M., Bulitta, J. B., Holzgrabe, U., Drusano, G. L., ...
Flucloxacillin is often used for the treatment of serious infections due to sensitive staphylococci. The pharmacokinetic (PK)-pharmacodynamic (PD) breakpoint of flucloxacillin has not been determined...
Heine, H. S., Byrne, W. R., Bassett, J., Miller, L., Drusano, G. L.
See also ADM001851, Proceedings of the 2003 Joint Service Scientific Conference on Chemical & Biological Defense Research, 17-20 November 2003. , The original document contains color images.
Deziel, Mark R., Heine, Henry, Louie, Arnold, Kao, Mark, Byrne, WIlliam R., Basset, Jennifer, ...
Expanded options for treatments directed against pathogens that can be used for bioterrorism are urgently needed. Treatment regimens directed against such pathogens can be identified only by using...
The Triple Combination Indinavir-Zidovudine-Lamivudine Is Highly Synergistic
Snyder, Stuart, D'Argenio, D. Z., Weislow, Owen, Bilello, John A., Drusano, G. L.
Administration of the combination of indinavir-zidovudine-lamivudine has been demonstrated to cause a large fraction of treated patients to have a decline in human immunodeficiency virus type 1...
Drusano, G. L., D'Argenio, D. Z., Preston, S. L., Barone, C., Symonds, W., LaFon, S., ...
The delineation of optimal regimens for combinations of agents is a difficult problem, in part because, to address it, one needs to (i) have effect relationships between the pathogen in question and...
A Population Pharmacokinetic Analysis of the Penetration of the Prostate by Levofloxacin
Drusano, G. L., Preston, S. L., Van Guilder, M., North, D., Gombert, M., Oefelein, M., ...
Prostatitis has remained a pathological entity that is difficult to treat. Part of the difficulty revolves about the putative offending pathogens. For acute prostatitis, members of the...
Drusano, G. L., Preston, S. L., Hardalo, C., Hare, R., Banfield, C., Andes, D., ...
One of the most challenging issues in the design of phase II/III clinical trials of antimicrobial agents is dose selection. The choice is often based on preclinical data from pharmacokinetic (PK)...
Drusano, G. L., Preston, S. L., Smee, D., Bush, K., Bailey, K., Sidwell, R. W.
We examined RWJ-270201 in a lethal model of influenza in BALB/c mice. The aim was to delineate the pharmacodynamically linked variable for the drug. Challenge was performed with influenza virus...
Drusano, G. L., D’Argenio, D. Z., Symonds, W., Bilello, P. A., McDowell, J., Sadler, B., ...
The use of combinations of anti-human immunodeficiency virus (anti-HIV) agents targeted to different molecular targets will most likely result in increased viral suppression and may also delay or...
Drusano, G. L., Preston, S. L., Gotfried, M. H., Danziger, L. H., Rodvold, K. A.
Levofloxacin was administered orally to steady state to volunteers randomly in doses of 500 and 750 mg. Plasma and epithelial lining fluid (ELF) samples were obtained at 4, 12, and 24 h after the...
Pharmacodynamics of Abacavir in an In Vitro Hollow-Fiber Model System
Drusano, G. L., Bilello, P. A., Symonds, W. T., Stein, D. S., McDowell, J., Bye, A., ...
Abacavir is a potent new carbocyclic nucleoside analogue. We employed our hollow-fiber pharmacodynamic modeling system to examine the antiretroviral effects of different abacavir exposures, as well...
Drusano, G. L., Moore, K. H. P., Kleim, J. P., Prince, W., Bye, A.
In order to choose a rational dose for GW 420867X, we first set a goal of therapy. We hypothesized that, for optimal antiretroviral activity, the trough free drug concentration should remain above...
Drusano, G L, Liu, W, Perkins, R, Madu, A, Madu, C, Mayers, M, ...
Robust determination of the concentration-time profile of anti-infective agents in certain specialized compartments is often limited by the inability to obtain more than a single sample from such a...
Population differences in ganciclovir clearance as determined by nonlinear mixed-effects modelling.
Yuen, G J, Drusano, G L, Fletcher, C, Capparelli, E, Connor, J D, Lalezari, J P, ...
We examined the pharmacokinetics of ganciclovir in different populations of cytomegalovirus (CMV)-infected patients through the use of nonlinear mixed-effects modelling. As expected, patient weight...
Bilello, J A, Bilello, P A, Kort, J J, Dudley, M N, Leonard, J, Drusano, G L
A-77003, a human immunodeficiency virus type 1 (HIV-1) protease inhibitor, is effective for both acute and chronic infection in vitro and was evaluated clinically by continuous intravenous infusion...
Drusano, G L, Prichard, M, Bilello, P A, Bilello, J A
We propose a method for the selection of doses and dosing schedule for drugs to be used in combination. This approach uses the simulation of steady-state concentrations of the drugs in the...
Bilello, J A, Bilello, P A, Stellrecht, K, Leonard, J, Norbeck, D W, Kempf, D J, ...
The therapeutic utility of a human immunodeficiency virus type 1 (HIV-1) protease inhibitor may depend on its intracellular concentration, which is a property of its uptake, metabolism, and/or...
We investigated the relationships between changes in CD4 lymphocytes counts over 24 weeks after the initiation of therapy with indinavir at dosages of > or = 2.4 g/day (n = 15) in human...
Effect of renal function on the bioavailability of ciprofloxacin.
Plaisance, K I, Drusano, G L, Forrest, A, Weir, M R, Standiford, H C
The effect of renal function on the bioavailability of ciprofloxacin was studied in 21 subjects with measured creatinine clearances ranging from 0 to 8.99 liters/h per 1.73 m2. Each subject received...
Pharmacokinetic evaluation of two dosage regimens of clindamycin phosphate.
Plaisance, K I, Drusano, G L, Forrest, A, Townsend, R J, Standiford, H C
Interpretation of the majority of data on the disposition of clindamycin is confounded by the presence of active metabolites, which may interfere with commonly employed bioassays. We undertook a...
Bustamante, C I, Drusano, G L, Wharton, R C, Wade, J C
The combinations of imipenem plus ciprofloxacin and imipenem plus amikacin were investigated for their activity against Pseudomonas aeruginosa and other bacterial pathogens. For imipenem-susceptible...
Bactericidal activity of ciprofloxacin compared with that of cefotaxime in normal volunteers.
Standiford, H C, Drusano, G L, Forrest, A, Tatem, B, Plaisance, K
We compared ciprofloxacin (200 mg) with cefotaxime (2 g) when each was administered intravenously over a 30-min period to six volunteers in a crossover manner 1 week apart. To integrate the...
Steady-state pharmacokinetics of imipenem in febrile neutropenic cancer patients.
Drusano, G L, Plaisance, K I, Forrest, A, Bustamante, C, Devlin, A, Standiford, H C, ...
We ascertained the pharmacokinetics of imipenem in febrile granulocytopenic cancer patients. The values observed were both different from and significantly more variable than those observed in normal...
Emergence of resistance to imipenem in Pseudomonas aeruginosa.
Lynch, M J, Drusano, G L, Mobley, H L
The emergence of resistance to imipenem by Pseudomonas aeruginosa was investigated with four pairs of isolates. Each pair represented pretherapy (susceptible) and posttherapy (resistant) specimens....
Relationships between renal function and disposition of oral ciprofloxacin.
Forrest, A, Weir, M, Plaisance, K I, Drusano, G L, Leslie, J, Standiford, H C
The relationships between creatinine clearance (CLCR) and the pharmacokinetics of oral ciprofloxacin were characterized. On the basis of these data, a dosage adjustment strategy, which incorporates...
Standiford, H C, Drusano, G L, Fitzpatrick, B, Tatem, B, Schimpff, S C
We compared the bactericidal activity of serum attained 1 and 6 h after the termination of infusions of either ceftazidime (2 g) or ticarcillin plus amikacin (5 g and 7.5 mg/kg, respectively) in 6...
Drusano, G L, Standiford, H C, Fitzpatrick, B, Leslie, J, Tangtatsawasdi, P, Ryan, P, ...
We compared ceftazidime with moxalactam, a commonly utilized, currently available drug. The microbiological activities of ceftazidime and moxalactam were studied. In addition, single-dose...
Steady-state serum pharmacokinetics of novobiocin and rifampin alone and in combination.
Drusano, G L, Townsend, R J, Walsh, T J, Forrest, A, Antal, E J, Standiford, H C
Because of the potential of novobiocin-rifampin for oral therapy of methicillin-resistant Staphylococcus aureus infection, we evaluated the pharmacokinetics of novobiocin and rifampin, alone and in...
Joshi, M, Anthony, W C, Tenney, J H, Drusano, G L, Caplan, E S, Standiford, H C, ...
Ceftazidime is a new antimicrobial agent possessing excellent in vitro activity against most members of the family Enterobacteriaceae and against Pseudomonas aeruginosa. We conducted a double-blind,...
Postantibiotic effect of imipenem on Pseudomonas aeruginosa.
Bustamante, C I, Drusano, G L, Tatem, B A, Standiford, H C
Imipenem (formerly N-formimidoyl thienamycin) and ceftazidime were investigated for their postantibiotic effect on Pseudomonas aeruginosa. Four strains of P. aeruginosa in the logarithmic phase of...
Effect of saturable clearance during high-dose mezlocillin therapy.
Drusano, G L, Forrest, A, Fiore, D, Auger, F, Caplan, E S
As mezlocillin has been shown to display nonlinear pharmacokinetics in single-dose evaluations, we evaluated a crossover trial in patients with renal dysfunction the impact on serum clearance of...
Multiple-dose pharmacokinetics of imipenem-cilastatin.
Drusano, G L, Standiford, H C, Bustamante, C, Forrest, A, Rivera, G, Leslie, J, ...
We characterized the pharmacokinetic profile of imipenem-cilastatin administered intravenously to six normal volunteers in a dose of 1,000 mg of each drug every 6 h for 40 doses. The plasma...
Fiore, D, Auger, F A, Drusano, G L, Dandu, V R, Lesko, L J
A rapid, sensitive, and specific method of analysis for mezlocillin in serum and urine by high-pressure liquid chromatography is described. A solid-phase extraction column was used to remove...
Drusano, G L, Joshi, J, Forrest, A, Ruxer, R, Standiford, H, Leslie, J, ...
We administered 2 g of ceftazidime intravenously every 8 h to cancer patients for the empiric therapy of febrile episodes. Ceftazidime was administered as monotherapy for patients with granulocyte...
Multiple-dose pharmacokinetics of ciprofloxacin administered intravenously to normal volunteers.
Gonzalez, M A, Moranchel, A H, Duran, S, Pichardo, A, Magana, J L, Painter, B, ...
We administered multiple doses of ciprofloxacin intravenously over 30 min every 12 h for 1 week to nine healthy volunteers. Three volunteers received a placebo (vehicle) intravenously. Doses of 100,...
Morris, J G, Tenney, J H, Drusano, G L
The in vitro activity of norfloxacin and six other antimicrobial agents was tested against 93 vibrio strains representing the currently described pathogenic Vibrio species. Norfloxacin had excellent...
Standiford, H C, Drusano, G L, Bustamante, C I, Rivera, G, Forrest, A, Tatem, B, ...
We administered 1 g of imipenem along with equal amounts of cilastatin (a dehydropeptidase I inhibitor) or 2 g of moxalactam intravenously over a period of 30 min to six volunteers in a crossover...
Dose ranging study and constant infusion evaluation of ciprofloxacin.
Drusano, G L, Plaisance, K I, Forrest, A, Standiford, H C
We evaluated the pharmacokinetics of 100- and 200-mg doses of ciprofloxacin, with the 200-mg dose administered either as a 30-min infusion or as a 100-mg loading dose followed by a 4-h constant...
Absolute oral bioavailability of ciprofloxacin.
Drusano, G L, Standiford, H C, Plaisance, K, Forrest, A, Leslie, J, Caldwell, J
We evaluated the absolute bioavailability of ciprofloxacin, a new quinoline carboxylic acid, in 12 healthy male volunteers. Doses of 200 mg were given to each of the volunteers in a randomized,...
Lactobacillus prophylaxis for diarrhea due to enterotoxigenic Escherichia coli.
Clements, M L, Levine, M M, Black, R E, Robins-Browne, R M, Cisneros, L A, Drusano, G L, ...
In vitro and animal experiments indicated that lactobacilli might prevent Escherichia coli from colonizing the intestine and may produce substances counteracting enterotoxin. Lactinex, a commercial...
Optimal Sampling Schedule Design for Populations of Patients
Tam, Vincent H., Preston, Sandra L., Drusano, G. L.
Generation of pharmacodynamic relationships in the clinical arena requires estimation of pharmacokinetic parameter values for individual patients. When the target population is severely ill, the...
Kort, J J, Bilello, J A, Bauer, G, Drusano, G L
A synthetic, symmetry-based inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease, A77003, was evaluated for antiviral activity and cytotoxicity in vitro in human peripheral blood...
Drusano, G L, Johnson, D E, Rosen, M, Standiford, H C
We examined the impact of dose fractionation and altered MICs on survivorship in a neutropenic rat model of Pseudomonas aeruginosa sepsis employing the new fluoroquinolone antibiotic lomefloxacin....
Bilello, J A, Bauer, G, Dudley, M N, Cole, G A, Drusano, G L
We sought to validate an in vitro system which could predict the minimal effect dose of antiretroviral agents. Mixtures of uninfected CEM cells and CEM cells chronically infected with human...
Drusano, G L, Yuen, G J, Morse, G, Cooley, T P, Seidlin, M, Lambert, J S, ...
The objective of this study was to determine the population pharmacokinetic parameters and the extent of absorption of 2',3'-dideoxyinosine, a nucleoside analog with activity against human...
Trifillis, A L, Cui, X, Drusano, G L
Foscarnet is an antiviral agent used for the treatment of cytomegalovirus retinitis and acyclovir-resistant herpes simplex virus infections in AIDS patients. Renal impairment has been reported for...
Measurement of amikacin in serum by a latex agglutination inhibition test.
Khabbaz, R F, Standiford, H C, Bernstein, D, Nipper, H C, Tatem, B A, Smalls, U, ...
Levels of amikacin in serum were determined in 106 serum specimens by a latex agglutination inhibition card test and by radioimmunoassay (RIA). Linear regression analysis demonstrated a high degree...
Drusano, G L, Weir, M, Forrest, A, Plaisance, K, Emm, T, Standiford, H C
We examined the pharmacokinetic behavior of 200 mg of ciprofloxacin administered intravenously to 32 volunteers whose renal function as measured by creatinine clearance ranged from 0 to 8.99 liters/h...
Effect of dose size on bioavailability of ciprofloxacin.
Plaisance, K I, Drusano, G L, Forrest, A, Bustamante, C I, Standiford, H C
We evaluated the bioavailability of ciprofloxacin at two dose sizes in eight healthy volunteers. Each volunteer was given 200 mg of ciprofloxacin both orally and intravenously in a randomized...
Impact of dosing schedule upon suppression of a retrovirus in a murine model of AIDS encephalopathy.
Bilello, J A, Eiseman, J L, Standiford, H C, Drusano, G L
We studied the impact of zidovudine (AZT) in Cas-Br-M murine leukemia virus-infected NFS-N mice after administration by once-daily bolus or continuous infusion. While higher peak concentrations of...
Quantitative relationships between zidovudine exposure and efficacy and toxicity.
Drusano, G L, Balis, F M, Gitterman, S R, Pizzo, P A
We examined the relationship between the concentrations of zidovudine in plasma given by continuous intravenous infusion to human immunodeficiency virus-positive pediatric patients and a surrogate...
Lomaestro, Ben M., Drusano, G. L.
A Monte Carlo simulation demonstrated that 1 g of meropenem (MEM) every 8 h (q8h) (3-h infusion) has a higher target attainment rate against Pseudomonas aeruginosa than either 500 mg of MEM q8h (3-h...
Deziel, Mark R., Heine, Henry, Louie, Arnold, Kao, Mark, Byrne, William R., Basset, Jennifer, ...
Expanded options for treatments directed against pathogens that can be used for bioterrorism are urgently needed. Treatment regimens directed against such pathogens can be identified only by using...
Chen, M., Nafziger, A. N., Drusano, G. L., Ma, L., Bertino, J. S.
Little is known of the effects of obesity on ertapenem drug disposition and pharmacodynamics. Thirty healthy volunteers in three body mass index (BMI) groups (10 per group), normal weight (BMI, 18.5...
The Triple Combination Indinavir-Zidovudine-Lamivudine Is Highly Synergistic
Snyder, Stuart, D'Argenio, D. Z., Weislow, Owen, Bilello, John A., Drusano, G. L.
Administration of the combination of indinavir-zidovudine-lamivudine has been demonstrated to cause a large fraction of treated patients to have a decline in human immunodeficiency virus type 1...
Drusano, G. L., D'Argenio, D. Z., Preston, S. L., Barone, C., Symonds, W., LaFon, S., ...
The delineation of optimal regimens for combinations of agents is a difficult problem, in part because, to address it, one needs to (i) have effect relationships between the pathogen in question and...
A Population Pharmacokinetic Analysis of the Penetration of the Prostate by Levofloxacin
Drusano, G. L., Preston, S. L., Van Guilder, M., North, D., Gombert, M., Oefelein, M., ...
Prostatitis has remained a pathological entity that is difficult to treat. Part of the difficulty revolves about the putative offending pathogens. For acute prostatitis, members of the...
Drusano, G. L., Preston, S. L., Hardalo, C., Hare, R., Banfield, C., Andes, D., ...
One of the most challenging issues in the design of phase II/III clinical trials of antimicrobial agents is dose selection. The choice is often based on preclinical data from pharmacokinetic (PK)...
Drusano, G. L., Preston, S. L., Smee, D., Bush, K., Bailey, K., Sidwell, R. W.
We examined RWJ-270201 in a lethal model of influenza in BALB/c mice. The aim was to delineate the pharmacodynamically linked variable for the drug. Challenge was performed with influenza virus...
Drusano, G. L., D’Argenio, D. Z., Symonds, W., Bilello, P. A., McDowell, J., Sadler, B., ...
The use of combinations of anti-human immunodeficiency virus (anti-HIV) agents targeted to different molecular targets will most likely result in increased viral suppression and may also delay or...
Drusano, G. L., Preston, S. L., Gotfried, M. H., Danziger, L. H., Rodvold, K. A.
Levofloxacin was administered orally to steady state to volunteers randomly in doses of 500 and 750 mg. Plasma and epithelial lining fluid (ELF) samples were obtained at 4, 12, and 24 h after the...