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2.  Pharmacokinetics and tissue penetration of ticarcillin combined with clavulanic acid. 
A combination of 3 g of ticarcillin and 200 mg of clavulanic acid was administered intravenously to six healthy male volunteers, after which the concentrations of these agents in serum and blister fluid were measured. The ratio of the two drugs in serum varied from 15:1 (ticarcillin-clavulanic acid) at the time of administration to 28:1 at 30 min and 62:1 at 5 h after injection. Both agents penetrated blister fluid rapidly, the ratio being 33:1 at 1 h and 66:1 at 3 h. The elimination rates of these agents were different, but for each compound they were similar in serum and blister fluid.
PMCID: PMC184977  PMID: 6614890
3.  Pharmacokinetics and tissue penetration of ceftibuten. 
The pharmacokinetics of the cephalosporin ceftibuten were determined after the fifth and final dose of 200 mg given every 12 h. Concentrations in plasma and cantharidin-induced inflammatory fluid were determined by a microbiological assay. Samples for three volunteers were assayed by a high-performance liquid chromatographic procedure to determine levels for both cis and trans ceftibuten. The mean peak level of ceftibuten in serum was 10.9 micrograms/ml at a mean time of 1.8 h after administration, and the mean elimination half-life from plasma was 2.5 h. Penetration into the inflammatory fluid was good, the mean peak level being 9.2 micrograms/ml at a mean time of 3.7 h. The mean percent penetration into the inflammatory fluid was 113.4%. High-performance liquid chromatography analysis showed that the mean peak level of the trans isomer was 5.7% that of the cis isomer. This study suggests that twice-daily doses of ceftibuten should be sufficient to treat urinary or systemic infections caused by susceptible pathogens.
PMCID: PMC171757  PMID: 2393265
4.  Pharmacokinetics and tissue penetration of carumonam, a new synthetic monobactam. 
The pharmacokinetics of the monobactam carumonam (Ro 17-2301) as derived from serial measurement of the concentrations of this agent in serum, blister fluid, and urine were studied in six male volunteers subsequent to intravenous infusion of a single 2-g dose. Drug levels in serum in excess of 75 micrograms/ml were achieved 0.5 h after the end of infusion, declining to 2.9 micrograms/ml at 8 h. The mean serum and blister fluid elimination half-lives were 1.68 and 1.7 h, respectively. The urinary recovery of the drug by 24 h was 80.6% (range, 68.3 to 91.1%). Carumonam penetrated blister fluid well, the mean percentage penetration (as measured by the ratio of areas under curves) being 101.6%.
PMCID: PMC180266  PMID: 4073864
5.  Pharmacokinetics and tissue penetration of enoxacin. 
The pharmacokinetics of the quinolone enoxacin were studied after a 600-mg oral dose was given to each of six male volunteers. The levels of the compound were measured in serum, blister fluid, and urine. Absorption was variable, with peak levels (mean, 3.7 micrograms/ml) being attained between 0.75 and 3.0 h (mean, 1.9 h). The serum elimination half-life was 6.2 h, and 71.6% of the drug was recovered in the urine by 48 h. Enoxacin penetrated blister fluid well, the mean percent penetration being 78.4%.
PMCID: PMC179907  PMID: 6591851
6.  In vitro activity of fludalanine combined with pentizidone compared with those of other agents. 
The in vitro activity of fludalanine ( MK641 ) combined with pentizidone ( MK642 ) so as to give a fludalanine /D-cycloserine ratio of 1:1 was compared with the activities of ampicillin, ticarcillin, cefuroxime, ceftazidime, and trimethoprim against 452 recent isolates and known beta-lactam- and trimethoprim-resistant strains. In addition, the in vitro activity of fludalanine - pentizidone on four different media, including a defined medium ( DFN -2), was studied. The MIC of fludalanine - pentizidone against 90% of Escherichia coli, Klebsiella spp., Enterobacter spp., Providencia stuartii, Haemophilus influenzae, Neisseria gonorrhoeae, Staphylococcus aureus, and fecal streptococci was 4 micrograms or less per ml on DFN -2, and activity was somewhat reduced on the other media. Proteus spp. and Pseudomonas aeruginosa (90% MIC, less than or equal to 64 micrograms/ml) and Bacteroides spp. (90% MIC, 16 micrograms/ml) were less susceptible. Generally, fludalanine - pentizidone was less active than ceftazidime and comparable in activity to cefuroxime. beta-Lactamase-producing and trimethoprim-resistant strains tended to be susceptible to fludalanine - pentidizone . In the absence of human serum, the MBC of fludalanine - pentizidone was similar to the MIC. In the presence of increasing concentrations of human serum, there tended to be a greater difference between the MIC and MBC.
PMCID: PMC185598  PMID: 6610389
7.  A study to determine the pharmacokinetics and inflammatory fluid penetration of two doses of a solid formulation of the hexetil prodrug of a trinem, sanfetrinem (GV 104326). 
The trinem sanfetrinem (GV 104326) was administered as the oral hexetil prodrug GV 118819X in two dose levels to six healthy volunteers. A single dose equivalent to 125 mg of sanfetrinem was administered, followed 6 weeks later by a single dose equivalent to 500 mg of sanfetrinem. The concentrations of the drug in plasma, cantharidin-induced inflammatory fluid, and urine were measured with a microbiological assay. The stability of sanfetrinem was studied in serum and inflammatory fluid. The mean peak concentrations in plasma of 0.77 and 2.47 microg/ml were attained at 1.1 and 2.0 h after the 125- and 500-mg doses, respectively. Mean peak concentrations in inflammatory exudate of 0.26 and 0.86 microg/ml were attained at 2.80 and 2.67 h after the 125- and 500-mg doses, respectively. The mean terminal elimination half-lives in plasma were 1.33 and 1.97 h for the 125- and 500-mg doses, respectively. The half-lives in the inflammatory fluid were 1.66 and 1.74 h for the 125- and 500-mg doses, respectively. The overall penetration of the drug into the inflammatory fluid was 51.4 and 47.0% for the 125- and 500-mg doses, respectively. Mean urine recovery was greater following 500 mg (24.15%) than after 125 mg (18.4%) of sanfetrinem. Sanfetrinem was relatively unstable in the inflammatory exudate in vitro (half-life, 5.5 h), and this could explain the poor penetration of the drug in the inflammatory exudate observed in this study.
PMCID: PMC164000  PMID: 9257756
8.  Pharmacodynamic properties of BAY 12-8039 on gram-positive and gram-negative organisms as demonstrated by studies of time-kill kinetics and postantibiotic effect. 
Time-kill kinetics of BAY 12-8039 were studied at two inocula against three strains each of Bacteroides fragilis, Escherichia coli, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pyogenes. The postantibiotic effects of BAY 12-8039 were studied on three strains each of E. coli, S. aureus, H. influenzae, Streptococcus pyogenes, and Streptococcus pneumoniae. The pharmacodynamic data demonstrated that BAY 12-8039 has marked activity against gram-positive and gram-negative organisms (under both anaerobic and aerobic conditions) and anaerobes. BAY 12-8039 also exhibited a postantibiotic effect of >1 h for all strains except one E. coli strain.
PMCID: PMC163919  PMID: 9174203
9.  In vitro activity of BAY 12-8039, a new fluoroquinolone. 
The in vitro activity of BAY 12-8039, a new fluoroquinolone, was studied in comparison with those of ciprofloxacin, trovafloxacin (CP 99,219), cefpodoxime, and amoxicillin-clavulanate against gram-negative, gram-positive, and anaerobic bacteria. Its activity against mycobacteria and chlamydia was also investigated. BAY 12-8039 was active against members of the family Enterobacteriaceae (MIC at which 90% of strains tested were inhibited [MIC90S] < or = 1 microgram/ml, except for Serratia spp. MIC90 2 microgram/ml), Neisseria spp. (MIC90S, 0.015 microgram/ml), Haemophilus influenzae (MIC90, 0.03 microgram/ml), and Moraxella catarrhalis (MIC90, 0.12 micrgram/ml), and these results were comparable to those obtained for ciprofloxacin and trovafloxacin. Against Pseudomonas aeruginosa, the quinolones were more active than the beta-lactam agents but BAY 12-8039 was less active than ciprofloxacin. Strains of Stenotrophomonas maltophilia were fourfold more susceptible to BAY 12-8039 and trovafloxacin (MIC90S, 2 micrograms/ml) than to ciprofloxacin. BAY 12-8039 was as active as trovafloxacin but more active than ciprofloxacin against Streptococcus pneumoniae (MIC90, 0.25 microgram/ml) and methicillin-susceptible Staphylococcus auerus (MIC90S, 0.12 micrograms/ml). The activity of BAY 12-8039 against methicillin-resistant S. aureus (MIC90, 2 micrograms/ml) was lower than that against methicillin-susceptible strains. BAY 12-8039 was active against anaerobes (MIC90S < or = 2 micrograms/ml), being three- to fourfold more active against Bacteroides fragilis, Prevotella spp., and Clostridium difficile than was ciprofloxacin. Against Mycobacterium tuberculosis, BAY 12-8039 exhibited activity comparable to that of rifampin (MICs < or = 0.5 micrograms/ml). Against Chlamydia trachomatis and Chlamydia pneumoniae BAY 12-8039 was more active (MICs < or = 0.12 microgram/ml) than either ciprofloxacin or erythromycin and exhibited a greater lethal effect than either to these two agents. The protein binding of BAY 12-8039 was determined at 1 and 5 micrograms/ml as 30 and 26.4%, respectively. The presence of human serum (at 20 or 70%) had no marked effect on the in vitro activity of BAY 12-8039.
PMCID: PMC163668  PMID: 8980763
10.  In vitro activity of the tricyclic beta-lactam GV104326. 
GV104326 is a novel tricyclic beta-lactam (a trinem or, formerly, tribactam). The in vitro activity of GV104326 was compared with those of cefuroxime, cefixime, amoxicillin, amoxicillin-clavulanic acid, cefpirome, and ciprofloxacin. GV104326 had in vitro activity generally similar to that of cefixime against members of the family Enterobacteriaceae (MIC at which 90% of the isolates are inhibited [MIC90], < or = 2 micrograms/ml), with cefuroxime and amoxicillin-clavulanic acid being 8- to 32-fold less active and with cefpirome being 4- to 8-fold more active against members of this family. The trinem had no activity against Pseudomonas aeruginosa or Stenotrophomonas maltophilia (MIC90, > 128 micrograms/ml) but was the most active agent against Acinetobacter calcoaceticus. GV104326 was particularly active against gram-positive cocci. Ninety percent of methicillin-susceptible Staphylococcus aureus strains were susceptible to 0.03 microgram of GV104326 per ml, making it the most active agent studied. Enterococci and Lancefield group A and B streptococci were generally equally or somewhat more susceptible to GV104326 than they were to amoxicillin. Streptococcus pneumoniae strains were highly susceptible to GV104326, and those strains which showed decreased susceptibility to penicillin were generally twofold more susceptible to the trinem than to amoxicillin. Haemophilus influenzae and Moraxella catarrhalis were highly susceptible to GV104326 (MIC90s, 0.12 and 0.03 microgram/ml, respectively). The anaerobes Clostridium perfringens, Bacteroides fragilis, and Peptostreptococcus spp. were more susceptible to the trinems (formerly tribactams) than to the other agents studied.
PMCID: PMC163300  PMID: 8723475
11.  Pharmacokinetics and penetration into inflammatory fluid of trovafloxacin (CP-99,219). 
A single 200-mg oral dose of trovafloxacin (CP-99,219) was given to each of eight healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharides-induced inflammatory fluid, and urine over the subsequent 36 h. The mean maximum concentration observed in plasma was 2.9 micrograms/ml at a mean time of 0.75 h postdose. The mean maximum concentration observed in inflammatory fluid was 1.2 micrograms/ml at 4.0 h postdose. The mean elimination half-life in plasma was 7.8 h. The overall penetration into inflammatory fluid was 64%, as assessed by determining the ratio of the area under the concentration-time curves. Recovery of the dose in urine within the first 36 h postdose was 5.0% of the administered dose. Our results indicate that trovafloxacin, at a dosage of 200 mg once or twice daily, should be adequate for the treatment of systemic infections caused by most common bacterial pathogens.
PMCID: PMC163054  PMID: 8787877
12.  Open-label crossover study to determine pharmacokinetics and penetration of two dose regimens of levofloxacin into inflammatory fluid. 
Antimicrobial Agents and Chemotherapy  1995;39(12):2749-2751.
Two levofloxacin administration regimens were used for six healthy male volunteers. They received either 500 mg of levofloxacin orally every 12 h for five doses or 500 mg every 24 h for three doses, and then 6 weeks later they received the other course. The concentrations of the drug in plasma, cantharidin-induced inflammatory fluid, and urine were measured with a microbiological assay following administration of the final dose. Mean peak concentrations in plasma of 9.3 and 6.6 micrograms/ml were attained 1.1 and 1.2 h after the 12- and 24-h regimens, respectively. Mean peak concentrations is inflammatory fluid of 6.8 and 4.3 micrograms/ml were attained at 2.3 and 3.7 h, respectively. The average steady-state concentrations were 5.0 and 2.2 micrograms/ml in plasma and 4.7 and 2.3 micrograms/ml in inflammatory fluid, respectively. The mean terminal elimination half-lives for plasma were 7.9 and 8.0 h for the two regimens, respectively, and the same values were noted for inflammatory fluid. The overall penetration into inflammatory fluid ranged from 88 to 101% with the 12-h regimen and 83 to 112% with the 24-h regimen. Mean urinary recoveries were 87 and 86% over the corresponding interval of the 12- and 24-h regimens, respectively. These results suggest that administration of levofloxacin once and twice daily should be efficacious for infections caused by the majority of pathogens.
PMCID: PMC163023  PMID: 8593013
13.  Pharmacokinetics and tissue penetration of the new fluoroquinolone grepafloxacin. 
A single 400-mg oral dose of grepafloxacin (OPC-17116) was given to each of six healthy male volunteers, and the concentrations of the drug in plasma, cantharides-induced inflammatory fluid, and urine were measured over the subsequent 12 h. The mean peak concentration in plasma of 1.5 micrograms/ml was attained at a mean time of 2.0 h postdose. The mean peak concentration in inflammatory fluid of 1.1 micrograms/ml was attained at a mean time of 4.8 h postdose. The mean elimination half-life in plasma was 5.2 h, and that in inflammatory fluid was 12.7 h. The overall penetration into inflammatory fluid was 180.6% (or 133% if one aberrant result from one volunteer is excluded). Recovery of the drug in urine during the first 24 h postdose was 8.3% of the administered dose. Our results indicate that a once- or twice-daily dosage of grepafloxacin should be adequate to treat systemic infections caused by most bacterial pathogens.
PMCID: PMC162569  PMID: 7726523
14.  Pharmacokinetics and distribution in tissue of FK-037, a new parenteral cephalosporin. 
Antimicrobial Agents and Chemotherapy  1994;38(10):2369-2372.
A single 1-g or 2-g intravenous dose of the cephalosporin FK-037 was given over 30 min in a cross-over-designed study, to each of six healthy male volunteers, and the concentrations of the drug were measured in plasma and cantharides-induced blister fluid over the subsequent 12 h. Urine was collected over 24 h. After a washout period of 6 weeks, during which the blisters healed, the study was repeated at the other dose level. Following the 1-g dose, the mean peak concentration in plasma was 83.8 micrograms/ml, and after the 2-g dose it was 142.6 micrograms/ml. The mean peak concentrations in the inflammatory fluid were 37.9 and 63.3 micrograms/ml, respectively. The mean elimination half-lives from plasma and inflammatory fluid were 2.0 and 2.5 h, respectively, after 1 g and 2.0 h and 3.7 h, respectively, after 2 g. The amounts of penetration into inflammatory fluid (as assessed by ratios of areas under the concentration-time curves) were 109.9 and 110.5% following doses of 1 and 2 g, respectively. The proportions of the administered drug recovered in the urine by 24 h were 87.6 and 85.7%, respectively. Our results indicate that FK-037 should prove to be efficacious in the treatment of a wide range of systemic infections.
PMCID: PMC284746  PMID: 7840572
15.  Pharmacokinetics of rufloxacin in patients with impaired renal function. 
The pharmacokinetics of rufloxacin were investigated in normal subjects and in patients with various degrees of renal failure after the administration of a single oral 400-mg dose. Twenty-four subjects were classified by glomerular filtration rate (GFR) normalized for body surface area. Group 1 subjects had GFRs of > 80 ml/min, group 2 subjects had GFRs from 30 to 80 ml/min, group 3 subjects had GFRs from 8 to 29 ml/min, and group 4 subjects had GFRs of < 8 ml/min. The patients in group 4 were on continuous peritoneal dialysis or underwent hemodialysis 48 h after dosing. Plasma and urinary rufloxacin concentrations were determined by high-performance liquid chromatography. A two-compartment model was used to calculate rufloxacin pharmacokinetic parameters. Apparent total body clearance of the drug was linearly related to GFR (r = 0.696; P < 0.01). The elimination half-life increased proportionally with the severity of renal impairment, with values of 30 +/- 3, 36 +/- 5, and 44 +/- 3 h in groups 1, 2, and 3, respectively. In patients with moderate renal failure, dosage adjustment of rufloxacin is not needed. The rufloxacin dose interval should be prolonged to 48 h as the GFR falls below 30 ml/min/1.73 m2.
PMCID: PMC187727  PMID: 8388194
16.  Antimicrobial susceptibilities and beta-lactamase characterization of Capnocytophaga species. 
Antimicrobial Agents and Chemotherapy  1992;36(10):2197-2200.
Capnocytophaga species have been associated with a wide variety of infections in both immunocompetent and immunocompromised patients. On the basis of data from antimicrobial susceptibility studies, beta-lactam antibiotics have been considered efficacious therapy. Six of 19 isolates from primarily clinical sources across Canada demonstrated beta-lactamase production, and agar dilution susceptibility testing showed broad resistance to beta-lactam antibiotics. For the beta-lactamase producing isolates, clavulanate reduced the MIC of amoxicillin for 90% of the strains tested by 64-fold. Isolates were highly susceptible to clindamycin, imipenem, and ciprofloxacin. Characterization of the beta-lactamases produced by two of these isolates (Van1 and Van2) was performed. Isoelectric focusing revealed an identical isoelectric point of 5.6 for both enzymes, but they had markedly different relative hydrolysis efficiencies, and different conditions were required to extract the enzymes. This study demonstrates the production of different types of beta-lactamases by Capnocytophaga spp. and suggests the need to screen all clinical isolates of Capnocytophaga spp. for the presence of beta-lactamases.
PMCID: PMC245475  PMID: 1444299
18.  Pharmacokinetics and tissue penetration of tazobactam administered alone and with piperacillin. 
The pharmacokinetics of tazobactam (500 mg) administered intravenously alone were compared with the pharmacokinetics of tazobactam coadministered with piperacillin (4 g), and the penetration into an inflammatory exudate in six healthy males was studied. Piperacillin influenced the pharmacokinetics of tazobactam. The mean levels of tazobactam in plasma at 4 h were 0.6 microgram/ml when it was given alone and 1.2 micrograms/ml when it was given with piperacillin (P = 0.0003). The mean total clearances of tazobactam were 203.5 and 134.2 ml/min (P = 0.035) when it was given alone and with piperacillin, respectively There were no significant differences in the elimination half lives, areas under the concentration-time curve from 0 h to infinity, or volumes of distribution. Inflammatory exudate penetration was rapid, and the mean maximum levels of tazobactam attained were 6.4 and 11.3 micrograms/ml when it was given alone or with piperacillin, respectively (P less than 0.06). The mean percent penetration of tazobactam and the area under the concentration-time curve from 0 h to infinity in inflammatory exudate were greater when tazobactam was given with piperacillin. The mean 24-h urinary recoveries of tazobactam were 63.7% +/- 7.9% when it was given alone and 56.8% +/- 2.7% when it was given with piperacillin. The explanation for the differences in the pharmacokinetics of tazobactam when it was administered alone compared with those when it was given with piperacillin was unclear.
PMCID: PMC284290  PMID: 1656853
19.  In vitro activity of a catechol-substituted cephalosporin, GR69153. 
The in vitro activity of GR69153, a new catechol-substituted cephalosporin, was compared with those of ceftazidime, imipenem, meropenem, and ceftriaxone against 604 recent clinical isolates and other strains with known mechanisms of resistance. The MICs of GR69153 for 90% of the members of the family Enterobacteriaceae tested were less than 0.5 micrograms/ml, with the exceptions of those for Serratia spp. (4 micrograms/ml), Citrobacter spp. (2 micrograms/ml), and Enterobacter spp. (8 micrograms/ml). Ninety percent of Pseudomonas aeruginosa isolates were susceptible to less than or equal to 1 microgram of GR69153 per ml. With the exception of methicillin-resistant strains, 90% of Staphylococcus aureus isolates were susceptible to less than or equal to 2 micrograms/ml, and GR69153 was four- to eightfold more active than ceftazidime and ceftriaxone against these strains. Isolates of Haemophilus influenzae, Branhamella catarrhalis, Neisseria spp., and Streptococcus pneumoniae (penicillin susceptible) were highly susceptible (MIC for 90% of the strains, less than or equal to 0.12 micrograms/ml). GR69153 was stable to hydrolysis by the TEM-1 and TEM-5, SHV-1 and SHV-2, and K1 beta-lactamases, but some susceptibility to hydrolysis by the TEM-3, TEM-9, and P99 enzymes was observed. The protein-binding activity of GR69153 was 74.5 to 66.8%, depending on the concentration, and serum had little effect upon activity.
PMCID: PMC245000  PMID: 2024966
20.  Meropenem pharmacokinetics and penetration into an inflammatory exudate. 
The pharmacokinetics and penetration into a cantharidine-induced inflammatory exudate of meropenem was studied in six volunteers following a single 1-g intravenous dose. Concentrations in plasma, urine, and the inflammatory exudate were determined by a microbiological assay. The mean elimination half-life of meropenem in plasma was 1.1 h, with the concentration in plasma declining from a mean of 23.6 micrograms/ml at 1 h to 0.7 micrograms/ml at 6 h. The inflammatory fluid penetration was rapid (time to maximum concentration of drug in serum, 0.75 h), and the penetration was 111%. The recovery of meropenem in urine at 24 h was 65.4% of the administered dose.
PMCID: PMC171864  PMID: 2221860
21.  Concentrations of oral lomefloxacin in serum and bronchial mucosa. 
The bronchial mucosal concentrations of lomefloxacin were determined for specimens obtained by fiber-optic bronchoscopy and compared with simultaneous concentrations in serum. The 23 patients studied were given an oral dose of 400 mg once daily for 4 days to achieve steady-state levels. The median concentration in serum was 2.5 micrograms/ml (range, 1.0 to 5 micrograms/ml), and the median bronchial mucosal concentration was 5.0 micrograms/g (range, 0.7 to 18.6 micrograms/g). The median percent penetration was 177% (range, 69 to 541%). The concentrations in serum and mucosa exceeded the MIC for 90% of strains of organisms causing bronchial infections but not sufficiently to recommend lomefloxacin for the routine treatment of pneumococcal infections.
PMCID: PMC171749  PMID: 2393260
22.  In vitro activity of Bay v 3522, a new cephalosporin, compared with activities of other agents. 
The in vitro activity of Bay v 3522, a new aminobenzothiazol cephem, was compared with those of other oral beta-lactams. Bay v 3522 displayed high activity against Staphylococcus spp. (MICs for 90% of strains tested [MIC90S], 0.5 micrograms/ml), Streptococcus pneumoniae (MIC90, 0.06 micrograms/ml), and Haemophilus influenzae and Branhamella catarrhalis (MIC90S, 2 micrograms/ml). There was limited activity against members of the family Enterobacteriaceae, with the MIC90S being between 4 and greater than 128 micrograms/ml. The stability of Bay v 3522 to hydrolysis by the SHV-1 and TEM-1 enzymes was intermediate to those of cephalexin (least hydrolyzed) and cefaclor, but it was markedly more stable than amoxicillin. There was high affinity to the chromosomally mediated P99 enzyme. The protein binding of Bay v 3522 was 45%. The primary target of Bay v 3522 was penicillin-binding protein 3.
PMCID: PMC171697  PMID: 2360820
23.  Pharmacokinetics and inflammatory fluid penetration of cefpodoxime proxetil in volunteers. 
The pharmacokinetics of cefpodoxime were determined after a single oral dose of 261 mg of cefpodoxime proxetil, equivalent to 200 mg of cefpodoxime, was given to each of six healthy male volunteers. Concentrations in serum, urine, and cantharidin-induced inflammatory fluid were measured by a microbiological assay. The mean peak level in plasma was 2.1 micrograms/ml, attained at a mean time of 2.9 h. The mean half-life of elimination from serum was 2.2 h. The inflammatory exudate was penetrated moderately rapidly, the mean peak level being 1.7 micrograms/ml at 3.5 h. The mean percent penetration of the inflammatory exudate was 103.7. The mean 24-h urine recovery of cefpodoxime was 32.2%. This study suggests that cefpodoxime proxetil taken once or twice daily will be sufficient to treat urinary or systemic infections caused by susceptible pathogens.
PMCID: PMC171563  PMID: 2327771
24.  In vitro activity of PD 127,391, an enhanced-spectrum quinolone. 
The in vitro activity of PD 127,391, a dihalogenated quinolone, was compared with those of ofloxacin, ciprofloxacin, nalidixic acid, gentamicin, and cefuroxime against 525 recent isolates and well-characterized antimicrobial agent-resistant strains. The MICs of PD 127,391 against 90% of members of the family Enterobacteriaceae, Bacteroides fragilis, Haemophilus influenzae, Neisseria sp., and Streptococcus pneumoniae were less than or equal to 0.12 microgram/ml. Some 90% of Pseudomonas aeruginosa and staphylococci were susceptible to 0.25 micrograms of PD 127,391 per ml. Against most strains, PD 127,391 was 2- to 8-fold more active than ciprofloxacin, but it was 64-fold more active than ciprofloxacin against B. fragilis. Strains of members of the family Enterobacteriaceae which were resistant to nalidixic acid were less susceptible to all of the quinolones tested, including PD 127,391. The MIC and minimum lethal concentration of PD 127,391 against three strains of Chlamydia trachomatis were each 0.06 microgram/ml, and the MIC against 90% of 21 strains of Mycobacterium tuberculosis was 1 microgram/ml. PD 127,391 was less active at pH 5, its maximal activity being at pH 7 to 8. The presence of urine at pH 5.9 decreased the bactericidal activity. The protein binding of PD 127,391 was 2 to 7%, and serum had little effect on activity.
PMCID: PMC172387  PMID: 3142350
25.  Pharmacokinetics and tissue penetration of roxithromycin after multiple dosing. 
The pharmacokinetics of the macrolide roxithromycin (RU 28965) were studied during and after administration of 150 mg every 12 h for 3 days (five doses) in six volunteers. The concentrations in serum, blister fluid, and urine were measured. Mean levels in serum taken at 1.5 h after the morning dose increased from 4.4 micrograms/ml on day 1 to 5.9 micrograms/ml on day 2 and 7.4 micrograms/ml on day 3. The mean serum and blister fluid elimination half-lives on day 3 were 13.2 and 12.5 h, respectively. Roxithromycin penetrated blister fluid well; the mean percent penetration (as measured by the ratio of areas under the curve) was 85%. After the final dose, a mean of 10.5% of that dose was recovered in 12 h as microbiologically active compound.
PMCID: PMC174870  PMID: 3662470

Results 1-25 (61)