Abstract:
:Composite data describing ocular pharmacokinetics are unreliable because of intersubject variation. To address this problem, an animal model was developed in which multiple aqueous samples from single subjects were obtained. Following direct anterior chamber or intravenous administration of amikacin or chloramphenicol, pharmacokinetic analysis of drug concentrations in the serum and anterior chamber was performed by using a nonlinear least-squares regression program. The number of anterior chamber paracenteses performed did not alter the beta elimination rates or percent penetration into the anterior chamber. The aqueous humor and peripheral-compartment terminal slopes were identical. These data indicate that complete ocular concentration-time curves can be obtained without altering antibiotic pharmacokinetics. Following direct injection into the anterior chamber, the elimination rates for both antibiotics followed a one-compartment model, whereas those following intravenous administration best fit an open, first-order, two-compartment model. Following intravenous administration, the anterior chamber elimination rate constants for both drugs were equal to that of the serum and significantly longer than that following direct injection. The elimination rates of both drugs following direct injection were similar. Systemic administration resulted in drug levels in aqueous humor that persisted longer than those following direct injection. Chloramphenicol, a lipophilic compound, gave higher mean concentrations in aqueous humor than did amikacin. Our model provides a new approach which rigorously examines ocular pharmacokinetics and provides data which suggest that for selected compounds the parenteral route of administration is preferable.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Mayers M,Rush D,Madu A,Motyl M,Miller MHdoi
10.1128/aac.35.9.1791subject
Has Abstractpub_date
1991-09-01 00:00:00pages
1791-8issue
9eissn
0066-4804issn
1098-6596journal_volume
35pub_type
杂志文章abstract::A fluoroquinolone (FQ) resistance rate of 5.9% is reported in 205 Mycobacterium tuberculosis isolates from patients presenting to field clinics in Karachi, Pakistan (2006 to 2009). FQ resistance among multidrug-resistant (MDR) strains was 11.1% (5/45), and it was 4.9% (5/103) in M. tuberculosis strains susceptible to ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00931-10
更新日期:2011-02-01 00:00:00
abstract::The aminoglycoside-modifying enzymes present in the first 120 clinical isolates harboring extended-spectrum beta-lactamases isolated in Spain were studied. Most of these isolates (84%) were gentamicin resistant. The enzymes most frequently associated and cotransferred with SHV-2 or TEM-type beta-lactamases were AAC(3)...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.11.2536
更新日期:1992-11-01 00:00:00
abstract::The gene coding for aminoglycoside 2'-N-acetyltransferase Ia [AAC(2')-Ia] from Providencia stuartii was amplified by PCR and cloned. The resulting construct, pACKF2, was transferred into Escherichia coli for overexpression of AAC(2')-Ia as a fusion protein with an N-terminal hexa-His tag. The fusion protein was isolat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.8.2238-2244.2001
更新日期:2001-08-01 00:00:00
abstract::The dependence of microbial killing on chloride ions present in solutions undergoing iontophoresis is addressed. A 400-microA current was applied to vials containing synthetic urine or saline, and the production of chlorine-based substances (CBSs) was detected by the N,N-diethyl-p-phenylene diamine colorimetric method...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.12.2768
更新日期:1994-12-01 00:00:00
abstract::A total of 18 strains of Mycobacterium fortuitum, 15 strains of M. chelonei, and 31 strains of M. chelonei-like organisms were tested by both broth microdilution and agar dilution to determine their susceptibility to 34 antimicrobial agents. All strains grew well enough in cation-supplemented Mueller-Hinton broth for ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.22.2.186
更新日期:1982-08-01 00:00:00
abstract::The pharmacokinetics of two prodrugs of zidovudine (AZT), 1,4-dihydro-1-methyl-3-[(pyridylcarbonyl)oxy] ester and isoleucinyl ester (DPAZT and IAZT, respectively), were investigated in a rabbit model to determine their potential utility as drugs against human immunodeficiency virus. Drugs were administered by intraven...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.4.818
更新日期:1993-04-01 00:00:00
abstract::Drug exposure or pharmacodynamic breakpoints refer to a magnitude of drug exposure which separates a population into groups with high and low probabilities of attaining a desired outcome. We used a pharmacodynamic model of disseminated candidiasis to define an in vivo drug exposure breakpoint for flucytosine (5FC) aga...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00369-06
更新日期:2006-11-01 00:00:00
abstract::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 ability to obtain traditional intensive blood sampling schedules is curtailed. Population modeling guided by optimal samplin...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.47.9.2888-2891.2003
更新日期:2003-09-01 00:00:00
abstract::The drug Ro5-3335 [7-chloro-5-(2-pyrryl)-3H-1,4-benzodiazepin-2(H)-one] inhibits human immunodeficiency virus type 1 (HIV-1) gene expression at the transcriptional level through interference with Tat-mediated transactivation (M.-C. Hsu, A. D. Schutt, M. Holly, L. W. Slice, M. I. Sherman, D. D. Richman, M. J. Potash, a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.12.2628
更新日期:1992-12-01 00:00:00
abstract::Due to the widespread resistance of bacteria to the available drugs, the discovery of new classes of antibiotics is urgently needed, and naturally occurring antimicrobial peptides (AMPs) are considered promising candidates for future therapeutic use. Amphibian skin is one of the richest sources of such AMPs. In the pr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00796-07
更新日期:2008-01-01 00:00:00
abstract::We previously reported the isolation of a laboratory-derived Staphylococcus aureus mutant, 523k, that has constitutive low-level resistance to vancomycin (MIC = 5 micrograms/ml) and teicoplanin (MIC = 5 micrograms/ml) and elaborates a ca. 39-kDa cytoplasmic protein that was not detected in the parent strain 523 (MIC =...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.1.166
更新日期:1996-01-01 00:00:00
abstract::Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains have spread worldwide and become a major threat in health care facilities. Transmission of blaKPC, the plasmid-borne KPC gene, can be mediated by clonal spread and horizontal transfer. Here, we report the complete nucleotide sequences of two nov...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02749-13
更新日期:2014-01-01 00:00:00
abstract::Penetration of fluconazole into female genital tissues was examined. Fluconazole was administered orally at a dose of 150 mg to patients undergoing total abdominal hysterectomy 1 to 151 h prior to surgery. During surgery, blood, uterus, ovary, and oviduct were sampled. Fluconazole concentrations in each tissue were de...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.43.1.148
更新日期:1999-01-01 00:00:00
abstract::Ceftaroline fosamil is a cephalosporin with activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The objective of this study was to characterize the dose-response relationship of ceftaroline fosamil against S. aureus in an immunocompromised murine pneumonia model, as ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01078-12
更新日期:2012-12-01 00:00:00
abstract::The new fluoroquinolone trovafloxacin was tested against a ciprofloxacin-sensitive, methicillin-resistant Staphylococcus aureus strain in the rabbit model of endocarditis. Trovafloxacin was more effective than vancomycin (CFU/g of vegetation, 2.65 +/- 1.87 versus 4.54 +/- 2.80 [mean +/- standard deviation]; P < 0.05) ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.12.3325
更新日期:1998-12-01 00:00:00
abstract::GSQ1530 is a compound derived from a newly identified class of antibiotics referred to as heteroaromatic polycyclic (HARP) antibiotics. The aim of this study was to assess the in vitro antimicrobial activity of GSQ1530. By using an NCCLS broth microdilution assay, the activities of GSQ1530 and other antibiotics were c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.10.3168-3174.2002
更新日期:2002-10-01 00:00:00
abstract::LYS228 is a novel monobactam with potent activity against Enterobacteriaceae LYS228 is stable to metallo-β-lactamases (MBLs) and serine carbapenemases, including Klebsiella pneumoniae carbapenemases (KPCs), resulting in potency against the majority of extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resis...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00552-18
更新日期:2018-09-24 00:00:00
abstract::Antifungal azoles are widely used for controlling fungal infections. Fungi are able to change the expression of many genes when they adapt to azole stress, and increased expression of some of these genes can elevate resistance to azoles. However, the regulatory mechanisms behind transcriptional adaption to azoles in f...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02244-13
更新日期:2014-01-01 00:00:00
abstract::Recent Food and Drug Administration (FDA) guidance endorses the use of an early clinical response endpoint as the primary outcome for community-acquired bacterial pneumonia (CABP) trials. While antibiotics will now be approved for CABP, in practice they will primarily be used to treat patients with community-acquired ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02632-13
更新日期:2014-07-01 00:00:00
abstract::The high levels of hepatitis B virus (HBV) surface antigen (HBsAg)-bearing subviral particles in the serum of chronically infected individuals are thought to play a role in suppressing the HBV-specific immune response. Current therapeutics are not directed at reducing this viral antigenemia; thus, our group has focuse...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00541-07
更新日期:2007-12-01 00:00:00
abstract::Although human immunodeficiency virus (HIV) coinfection is the most important risk factor for a poor antituberculosis (anti-TB) treatment response, its effect on the pharmacokinetics of the first-line drugs in children is understudied. This study examined the pharmacokinetics of the four first-line anti-TB drugs in ch...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.01701-16
更新日期:2017-01-24 00:00:00
abstract::Miltefosine (MT) is a membrane-active alkylphospholipid licensed for the topical treatment of breast cancer skin metastases and the oral treatment of leishmaniasis, although its mechanism of action remains unclear. Electron paramagnetic resonance (EPR) spectroscopy of a spin-labeled lipid and a thiol-specific spin lab...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01332-13
更新日期:2014-06-01 00:00:00
abstract::During a 4-month period in late 1988, we isolated ceftazidime-resistant strains of Klebsiella pneumoniae and other members of the family Enterobacteriaceae from 29 patients at a chronic-care facility in Massachusetts. Ceftazidime resistance resulted from two distinct extended-spectrum beta-lactamases of the TEM type w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.11.2193
更新日期:1990-11-01 00:00:00
abstract::Microbial metabolism studies of the antimalarial drug primaquine, using Streptomyces roseochromogenus (ATCC 13400) have produced an N-acetylated metabolite and a methylene-linked dimeric product, both of which have been previously reported, and a novel sulfur-containing microbial metabolite. The structure of the metab...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.30.2.234
更新日期:1986-08-01 00:00:00
abstract::N(2)-(3,4-Dichlorobenzyl)-7-(2-[1-morpholinyl]ethyl)guanine (MorE-DCBG, 362E) is a synthetic purine that selectively inhibits the replication-specific DNA polymerase of Clostridium difficile. MorE-DCBG and its analogs strongly inhibited the growth of a wide variety of C. difficile strains. When administered orally in ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.06097-11
更新日期:2012-03-01 00:00:00
abstract::The experimental pharmacoenhancer cobicistat (COBI), a potent mechanism-based inhibitor of cytochrome P450 3A enzymes, was found to inhibit the intestinal efflux transporters P-glycoprotein and breast cancer resistance protein. Consistent with its transporter inhibition, COBI significantly increased the absorptive flu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01089-12
更新日期:2012-10-01 00:00:00
abstract::Recent years have seen the rapid advancement of new therapeutic agents against hepatitis C virus (HCV) in response to the need for treatment that is unmet by interferon (IFN)-based therapies. Most antiviral drugs discovered to date are small molecules that modulate viral enzyme activities. In the search for highly sel...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01206-09
更新日期:2010-01-01 00:00:00
abstract::The in vitro pharmacodynamic properties of colistin and colistin methanesulfonate were investigated by studying the MICs, time-kill kinetics, and postantibiotic effect (PAE) against mucoid and nonmucoid strains of Pseudomonas aeruginosa isolated from patients with cystic fibrosis. Twenty-three clinical strains, includ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.3.781-785.2001
更新日期:2001-03-01 00:00:00
abstract::Conventional therapy for human cytomegalovirus (CMV) relies on inhibition of the viral DNA polymerase. Ganciclovir (GCV) is the first-line therapy, but when GCV-resistant strains emerge, alternative therapies are extremely limited and are associated with significant toxicities. Combination of anti-CMV agents that act ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01972-13
更新日期:2014-01-01 00:00:00
abstract::A series of [(aryl)arylsufanylmethyl]pyridines (AASMP) have been synthesized. These compounds inhibited hemozoin formation, formed complexes (K(D) = 12 to 20 muM) with free heme (ferriprotoporphyrin IX) at a pH close to the pH of the parasite food vacuole, and exhibited antimalarial activity in vitro. The inhibition o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00898-07
更新日期:2008-02-01 00:00:00